oversight

Food Tampering: FDA's Actions on Chilean Fruit Based on Sound Evidence

Published by the Government Accountability Office on 1990-09-06.

Below is a raw (and likely hideous) rendition of the original report. (PDF)

                          I~tlittvi   Statt3   (knt~ral   Acwnnting   Office
                          Report to the Ranking Minority                        -
GAO                       Member, Committee on Foreign
                          Relations, U.S. Senat.e


September   1990
                          FOOD TAMPERING
                          FDA’s Actions on
                          Chilean Fruit Based on
                          Sound Evidence




                             RErnIcTED--       Not to be released outside the
                             General Accounting OfEce unless specifically
                             approved by the OfTice of Congressional
                      I      Relationa

                      !               54s3 46
 <;AO,~‘HRD-90- 164
                     United States
GAO                  General Accounting  Office
                     Washington, D.C. 20548

                     Human Resources Division

                     B-239068

                     September 6, 1990

                     The Honorable Jesse Helms
                     Ranking Minority Member
                     Committee on Foreign Relations
                     United States Senate

                     Dear Senator Helms:

                     In March 1989, the U.S. Embassy in Chile received warnings that
                     Chilean fruit destined for the United States had been poisoned with cya-
                     nide. As a result, the Food and Drug Administration (FDA) increased its
                     inspection of Chilean fruit and, on March 12, 1989, found grapes that
                     contained cyanide. The grapes were found on a Chilean vessel that had
                     arrived in Philadelphia. Based on this finding, fruit imports from Chile
                     were suspended for 5 days, beginning March 13, while FDA developed a
                     more comprehensive inspection program for Chilean fruit. On March 17,
                     the suspension was lifted and all Chilean fruit that passed FDA'S inspec-
                     tion was allowed to enter U.S. markets.

                     In May 1989, you expressed concern about the justification for FDA'S
                     actions given their reported substantial economic impact and asked us to
                     review several issues relating to FDA'S discovery of cyanide in Chilean
                     grapes. In general, your request focused on the adequacy of the evidence
                     FDA used to support its decision that resulted in the temporary suspen-
                     sion of Chilean fruit imports to the United States.

                     As agreed with your office, we assessed whether       FDA,   in taking its
                     actions on Chilean fruit,

                   . used proper laboratory tests and procedures, including adequately safe-
                     guarding fruit samples;
                   . complied with the law and FDA regulations pertaining to adulterated
                     food products; and
                   . consulted with other federal agencies and affected parties before
                     arriving at its decisions.


Results in Brief     on generally accepted tests that were conducted properly. Based on its
                     finding, FDA acted within its legal authority to suspend imports of
                     Chilean fruit, and, although not required by law, FDA made its decision
                     after consulting with other federal agencies and affected parties,



                     Page 1                       GAO/HR.MO-164 FDA’s Actions on Poisoned Chilean Fruit
-   -.
             E-239068




             including the Departments of State and Agriculture, and representatives
             of the Chilean government and food industry.

             We did not identify any studies addressing the economic impact of FDA’s
             actions on the US. economy. Representatives of the Chilean fruit
             industry estimated that FDA'S actions cost the Chilean economy at least
             $333 million. We did not review the industry’s cost estimate and, there-
             fore, cannot express an opinion on its reliability. However, Chilean fruit
             exports to the United States in 1990, a year after the poisoning incident,
             reached an all time high, indicating that exports to the United States
             and other countries have not been seriously affected by the incident.


             The Federal Food, Drug, and Cosmetic Act requires that foods distrib-
Background   uted and sold in the United States be pure and wholesome, safe to eat,
             and produced under sanitary conditions. It prohibits the importation of
             any food that contains a poisonous or other harmful substance that may
             pose a health risk. Under the act and applicable regulations, FDA has
             been delegated responsibility from the Secretary of Health and Human
             Services for ensuring that imported food products it regulates meet the
             requirements of the act. The U.S. Customs Service shares responsibility
             for regulating imported foods in that it controls the entry of all imported
             products into the United States. Imported foods that fail to meet the
             requirements of the law are detained at the entry location and must be
             brought into compliance, destroyed, or removed from the United States.

             The United States is the largest single market for Chilean fruit. In the
             1990 season, about 56.5 million crates of Chilean fruit were sold in the
             United States. About 70 percent of Chile’s fruit shipments to the United
             States arrive at Philadelphia.

             On March 2, 1989, an unidentified person called the U.S. Embassy in
             Santiago, Chile, claiming to have poisoned fruit with cyanide that was
             being shipped to the United States and Japan. The Department of State
             told us that the Japanese Embassy and the Chilean Exporters Associa-
             tion in Chile also received a similar threat. The caller to the U.S.
             Embassy did not specify the type(s) of fruit poisoned or the vessel(s) on
             which the fruit was shipped. The Department of State notified the Cus-
             toms Service, which, in turn, notified FDA of this threat on March 3. As a
             precaution, that same day, the Customs Service ordered the detention of
             all Chilean fruit while it consulted with FDA. That hold was lifted on
             March 6, after FDA initially concluded the threat was a hoax. On March
             7, FDA began conducting experiments on fruits injected with cyanide. On


             Page 2                       GAO/HlUMO-164 FDA’s Actions on Poisoned Chilean Fruit
March 8, the U.S. Embassy in Chile received a second telephone call that
Chilean fruit had been poisoned and, consequently, FDA increased its
inspections of Chilean fruit at U.S. seaports. On March 10 and 11, three
ships containing Chilean fruit arrived in the United States. By March 12,
FDAhad examined about 1,200 crates of fruit when an FDA investigator
found three unusual-looking grapes in a crate unloaded from a ship (the
Almeria Star) docked in Philadelphia. FDA’S Philadelphia laboratory ana-
lyzed a grape sample and found it contained cyanide.

FDAdid not allow fruit from the Almeria Star to enter the country. Also,
it suspended Chilean fruit imports while it worked with other federal
agencies and Chilean representatives to develop an examination plan to
further increase inspections of fruit from Chile. The suspension lasted
for 5 days until FDAand Chilean representatives agreed on a plan to
inspect Chilean fruit imports and release fruit that passed inspection.
Although, on March 17, FDA was notified of a third telephone threat in
Chile, no additional contaminated fruit was found, and import inspec-
tions returned to normal by mid-April 1989.

Although a June 1990 study by the Chilean Exporters Association
reported a $333 million loss to the economy of Chile, there has been no
independent assessment of the actual impact.’ The Association reported
that this loss was due to lost revenue and extraordinary costs resulting
from the tampering incident. The Association defined lost revenue as
the difference between the value of fruit that Chile expected to export
in 1989 and the amount actually exported. Extraordinary costs include
costs to destroy fruit denied entry into the United States, interest and
financing costs for loan extensions and other methods used to finance
continued operations, increased inspection and security costs, and mis-
cellaneous expenses.

Figure 1 shows the chronology of key events during the course of the
tampering incident. More detailed information is in appendix IV.




‘We did not verify the Association’s study and, therefore, cannot express an opinion on it.



Page 3                                 GAO/IUU%JO-164 FDA’s Actions on Poisoned Chilean Fruit
                                                B-239068




Figure 1: Chronology   of Events During the Chilean Fruit Incident           (March 1989)


          Sunday             Monday             Tuesday              Wednesday                 Thursday                    Friday                 Saturday
                                                                 1                        2 First threat          3    Customs               4  Customs
                                                                                          telephoned to           detains Chilean            consufts with
                                                                                          U.S. embassy            ‘;rtAand notrfres          FDA




     5                  6  Customs lifts   zya;y4ebegins         8   Second               9                       10 FDA                     11   Almeria
                       hold on most                              threat tele-                                     decides to                 Star arrives in
                       fruit; FDA begins   experiments           phoned to U.S.                                   examine all                Phila.; FDA
                       to examine 10%                            embassy                                          other Chilean              begins
                       of large fruit                                                                             fruita                     examinationb



     12 FDA             13                 14                    15                       16                      17    FDA                  18 Industry
     discovers                                                                                                    notified of third          begins visual
     cyanide in                                                                                                   telephone threat           examination of
     grapes from                                                                                                                               rapes under
     Almeria Star                                                                                                                            F DA supervision
                                    FDA suspends fruit imports and develops an examination                      plan
                                                                                                                                    I
     19                 20                 21                    22   industry            23                      24 Industry                25
                                                                 begins visual                                    begins visual
                                                                 examination of                                   examination of
                                                                 pears and                                        most other fruits
                                                                 nectarines



     26                 27                 28                    29                       30                      31


                                                                 I        Industry reduces frequency of examinationsC


                                                aBound from Chile, the Spring Dewe arwes at Phlladelphla at 9 00 a m and the Kntl Rex arrives                   at Los
                                                Angeles at 5.00 p m at 6 00 p m FDA decides to inspect 2 percent of all other fruit

                                                t Almena Star left Chile on February      27, 1969, travelled   non-stop   to Phlladelphla    and arwed   13 days later
                                                on March 11

                                                ‘FDA   resumed   normal    inspection   levels on Apnl 14, 1969




                                                The  objectives of our review were to assess (1) the appropriateness of
Objectives, Scope, and                          FDA'S laboratory testing of fruit, (2) the legal propriety of FDA'S actions
Methodology                                     related to Chilean fruit, and (3) the extent to which FDA consulted with
                                                others regarding its proposed action on fruit imports. We also agreed to



                                                Page 4                                         GAO/HRMJO-164 FDA’s Actions on Poisoned Chilean Fruit
summarize any studies we identified on the economic impact of           FDA'S
actions on the U.S. and Chilean economies.

In conducting our review, we interviewed and obtained information
from officials of FDA, including the former FDA Commissioner; the Cus-
toms Service; the U.S. Department of Agriculture; the Federal Bureau of
Investigation (FBI); the State Department; the Chilean Exporters Associ-
ation; and import firms.

We used four outside consultants to evaluate the adequacy of FDA'S
testing and sample protection methods and to assess the reliability of
FDA'S findings. The Association of Official Analytical Chemists (the prin-
cipal authority on analytical chemical methods) assisted us in identi-
fying potential consultants. The consultants reviewed all of the
pertinent information related to the tests performed by FDA'S Philadel-
phia laboratory. They reviewed experimental studies conducted by FDA
and others, and accompanied us in interviewing Chilean fruit industry
scientists. The consultants also interviewed FDA staff, including the ana-
lysts who performed the tests that found cyanide contamination in a
sample of grapes. One of the consultants prepared a draft report on the
review of FDA'S testing and sample protection methods. The draft report
was reviewed by the other three consultants. The consultants’ findings
are contained in appendix V.

To evaluate FDA'S measures to safeguard the fruit sample found to con-
tain cyanide, we reviewed the adequacy of FDA'S sample identification
and protection procedures. In addition, we sought the views of the FBI
and the consultants we hired on this matter.

To determine whether FDA'S actions were consistent with applicable law
and regulations, we reviewed court decisions and administrative deci-
sions interpreting the applicable statutes.

We performed our work between October 1989 and April 1990 in accor-
dance with generally accepted government auditing standards. The
results of our work are summarized below and discussed more fully in
appendixes I through III.




Page 5                       GAO/HFlD90-164 FDA’s Actions on Poisoned Chilean Fruit
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                      EL-239068




                      After the suspension of Chilean fruit imports, controversy arose over
FDA’s Laboratory      FDA'S handling of the situation. In particular, several news stories and
Testing and Sample    the Chilean fruit industry accused FDA of improperly conducting its labo-
Protection Were       ratory tests and of mishandling fruit samples. We found, however, after
                      extensively evaluating FDA'S laboratory testing procedures that FDA used
Proper                proper testing methods and adequately protected fruit samples from
                      being mishandled while in its possession. The laboratory tests and find-
                      ings were the basis for FDA'S actions on Chilean fruit imports.

                      FDA  used two widely accepted tests and conducted them in accordance
                      with sound scientific methods. One test, referred to as a cyantesmo test,
                      was initially done to screen the fruit for cyanide. In the instance where
                      this test identified cyanide, FDA conducted a second test, called the
                      chloramine-T test, to confirm the initial test results and to quantify the
                      amount of cyanide remaining in the fruit. To help assure that any cya-
                      nide present in the grapes or other fruit would not be lost during testing,
                      FDA modified the chloramine-T test. The need for this modification was
                      based on FDA'S experience with cyanide that had been placed in another
                      food product. FDA'S modified test yielded a valid finding that cyanide
                      was present in the grape sample.

                      Both our review and the FBI’Sinvestigation of the incident found that
                      the samples sent to FDA'S laboratory for testing were adequately pro-
                      tected against mishandling and contamination.


                      Upon finding grapes from the Almeria Star that contained a small
FDA’s Actions Were    amount of cyanide, FDA denied entry to the ship’s fruit; warned the
Consistent With Its   public not to eat Chilean fruit; increased inspections of subsequent
Legal Authority       Chilean fruit shipments and fruit already in cold storage; and recom-
                      mended that retail outlets and wholesalers remove Chilean fruit from
                      distribution. FDA'S actions were consistent with the Federal Food, Drug,
                      and Cosmetic Act, which requires that imported food be denied entry to
                      the United States when examination, sampling, or other evidence indi-
                      cates that the food appears to be adulterated. The act also allows FDA to
                      issue public warnings if an imported food presents a health hazard.
                      Although the level of cyanide detected in the grapes was not in itself
                      sufficient to cause illness, FDA determined that there was a distinct pos-
                      sibility that other fruit could also be contaminated and could result in
                      serious illness or death.




                      Page6                        GAO/IUD-90164FDA'sActioneonPoisonedChileanFruit
                         B-239068




                         The Federal Food, Drug, and Cosmetic Act does not require FDA to con-
FDA Consulted With       sult with other agencies in determining whether an imported food
Others on Its Proposed   product appears to be adulterated. Nor does the act require consultation
Act ions                 on how to remedy the problem.

                         Nevertheless, after determining that Chilean fruit aboard the Almeria
                         Star was adulterated, FDA consulted with officials from several federal
                         agencies, the Chilean government, and the fruit industry about the tam-
                         pering incident and actions needed to protect public health and lessen
                         the impact on Chile. The federal agency officials either agreed with
                         FDA's proposals or deferred any decision regarding Chilean fruit imports
                         t0 FDA.

                         The primary focus of FDA'S consultations with the Chilean government
                         and fruit industry officials was to develop an examination plan to
                         inspect Chilean fruit and allow fruit that passed inspection to enter the
                         market. On March 17, 1989, FDA and the Chileans agreed on an examina-
                         tion plan that called for industry-hired inspectors operating under FDA
                         supervision to examine 5 percent of all Chilean fruit; both fruit coming
                         into and fruit in cold storage in the United States that was shipped after
                         February 20, 1989. Since no further cyanide contamination was found,
                         FDA discontinued the increased inspection program on April 14, 1989.



                         As agreed, we did not obtain written agency comments on the report,
                         but discussed it with FDA and officials of the Department of State, the
                         Department of Agriculture, the Customs Service, and the FBI. Where
                         appropriate, we incorporated their comments into the report.

                         Unless you publicly announce its contents earlier, we plan no further
                         distribution of this report until 30 days after its issue date. At that time,
                         we will send copies to cognizant congressional committees; the Secretary
                         of Health and Human Services; and the Director, Office of Management
                         and Budget. We will also make copies available to others upon request.




                         Page 7                        GAO/HRLM&164 FDA’s Actions on Poisoned ChUean Fruit
B-239068




This report was prepared under the direction of Mark V. Nadel, Asso-
ciate Director, National and Public Health Issues, who may be reached
on (202) 275-6195. Other major contributors are listed in appendix VI.

Sincerely yours,




Lawrence H. Thompson
Assistant Comptroller General




Page 8                      GAO/HRD90164   FDA’s Actions on Poisoned Chilean Fruit
Page 9   GAO/HRMtO-164 FDA’s Actions on Poisoned Chilean Fruit
-

Contents


Letter                                                                                                       1

Appendix I                                                                                                  12
FDA’s Laboratory             Alleged Improprieties of FDA’s Laboratory Procedures
                             FDA Used Proper Test Methods and Procedures to Detect
                                                                                                            12
                                                                                                            12
Testing and Sample                Cyanide
Protection Were              FDA’s Modification of Test Was Appropriate                                     13
                             Sample Accountability and Protection Were Adequate                             14
Appropriate                  Studies Show Cyanide Can Be Injected Into Fruit and                            16
                                  Retained

Appendix II                                                                                                 18
FDA’s Actions                Law Prohibits Poisoned Food From Entering the United
                                 States
                                                                                                            18
Consistent With Law          FDA’s Actions Consistent With Actions Taken in Similar                         19
and Regulations                  Incidents

Appendix III                                                                                                21
FDA Consulted With           U.S. Agencies Consulted With Chilean Interests                                 21
Others Before Acting
Appendix IV                                                                                                 23
Chronology of Events         z;z”, i ; I$989                                                                23
                                                                                                            23
Relating to Poisoning        March 11 to 17                                                                 24
of Chilean Fruit             March 18 to April 14                                                           25
                         A

    Appendix V                                                                                              26
    Review of FDA            Consultants
                             Questions GAO Furnished to Four Consultants
                                                                                                            26
                                                                                                            26
    Testing Procedures       1. Introduction                                                                28
    Used to Determine        2. Procedure                                                                   29
                             3. Findings                                                                    29
    Cyanide in Chilean       4. Conclusion                                                                  40
    Fruit-Consultants’
    Report to GAO



                             Page 10                     GAO/HRD-90-164 FDA’s Actions on Poisoned Chilean Fruit
-
                        Contents




Appendix VI                                                                                               42
Major Contributors to
This Report
Figure                  Figure 1: Chronology of Events During the Chilean Fruit                             4
                             Incident (March 1989)




                        Abbreviations

                        FBI        Federal Bureau of Investigation
                        FDA        Food and Drug Administration
                        GAO        General Accounting Office
                        HHS        Department of Health and Human Services


                        Page 11                    GAO/HRD90164   FDA’s Actions   on   Poisoned Chilean Fruit
FDA’s Laboratory Testing and Sample
Protection Were Appropriate

                            FDA'S  actions that resulted in the temporary suspension of Chilean fruit
                            imports have been the subject of much controversy. This controversy
                            centered on whether FDA procedures and testing were appropriate to
                            detect cyanide contamination of the fruit. We found that FDA used two
                            widely accepted cyanide detection tests, properly protected the samples
                            against contamination, conducted the tests in accordance with appro-
                            priate scientific principles, and accurately analyzed the results. Thus,
                            we believe FDA inspections and laboratory testing procedures provided a
                            reasonable scientific basis for the subsequent actions it took on Chilean
                            fruit.


                            On March 12, 1989, FDA inspectors at the Tioga Fruit Terminal in Phila-
Alleged Improprieties       delphia identified three suspicious-looking grapes and sent them to FDA's
of FDA’s Laboratory         Philadelphia laboratory for testing and analysis. FDAdetermined that a
Procedures                  sample of two of the grapes contained cyanide. Subsequently, several
                            allegations were made by the news media and the Chilean fruit industry
                            that the laboratory tests were not properly conducted and analyzed. The
                            specific allegations were that FDA:

                        . used inappropriate  tests to determine the presence of cyanide in grapes;
                        l inappropriately modified a test, thereby invalidating the test’s results;
                        0 did not promptly record test results; and
                        l did not exercise adequate control to protect fruit samples against
                          contamination.

                            Additionally, it was alleged that cyanide could not be injected into
                            grapes and other fruit in Chile and be retained in the fruit after the 13
                            day trip to the United States, thereby implying that the grapes were
                            contaminated in the United States.


                            FDA'S Philadelphia laboratory used two different tests-the cyantesmo
FDA Used Proper Test        and chloramine-T tests-to detect and confirm the presence of cyanide
Methods and                 in the sample of suspicious-looking grapes. Both tests are widely used
Procedures to Detect        and accepted within the scientific community for detecting cyanide in
                            food. The cyantesmo test is a screening test that FDA initially used to
Cyanide                     detect the cyanide in the fruit. The test uses a specially treated paper
                            strip that turns blue when it reacts with hydrogen cyanide gas, indi-
                            cating the presence of cyanide.’

                            ‘An acid is added to fruit samples to convert cyanide that may be in samples into hydrogen cyanide
                            P=



                            Page 12                               GAO/HRD-SO-164      FDA’s Actions   on Poisoned Chilean Fruit
                        Appendix I
                        FDA’s Laboratory Testing and Sample
                        Protection Were Appropriate




                        FDA performed cyantesmo testing on approximately 75 suspicious-
                        looking fruit samples from the Almeria Star during March 11 and 12,
                        1989. A sample of grapes from that ship showed a positive reaction to
                        the cyantesmo test, indicating the presence of cyanide. A second FDA
                        analyst immediately repeated the test on this sample and obtained the
                        same positive reaction.

                        To confirm the initial finding and to quantify the amount of cyanide in
                        the grapes, FDA used the chloramine-T test. This test chemically converts
                        cyanide to a substance that absorbs light at a specific wavelength. It
                        determines the amount of cyanide in the fruit by measuring the quantity
                        of light absorbed with a spectrophotometer.

                        Based on the results of the chloramine-T test, the sample of two grapes
                        contained approximately 0.51 parts per million of cyanide (approxi-
                        mately 0.003 milligrams in a sample weighing 6 grams). This quantity is
                        well below a fatal dose.’ However, because hydrogen cyanide is a gas, an
                        indeterminate amount of the poison was unavoidably used up in pre-
                        paring and conducting the cyantesmo test. Thus, the amount of cyanide
                        measured by the chloramine-T test was less than the amount that was
                        actually present in the sample before testing. Because the Federal Food,
                        Drug, and Cosmetic Act prohibits the importation of any food product
                        that appears to be adulterated, FDA was mainly concerned with deter-
                        mining whether any fruit had been poisoned rather than in determining
                        the precise amount of poison present.


                        At the time of the tampering incident, FDA had no published procedures
FDA’s Modification of   for conducting a chloramine-T test to detect cyanide in fruit. However,
Test Was Appropriate    FDA did have published procedures for conducting the chloramine-T test
                        on other products, including a laboratory bulletin on conducting the test
                        to detect cyanide in tea. That procedure called for heating the sample
                        solution (distillation) to release cyanide gas. But, in preparing the grape
                        sample for the chloramine-T test, the FDA analyst modified the proce-
                        dure by separating grape solids from the liquid through centrifugation
                        rather than using the distillation method. The analyst made the modifi-
                        cation based on the Philadelphia laboratory’s recent experience
                        involving testing for cyanide in another food product. The laboratory
                        had found that distilling samples containing known quantities of cya-
                        nide resulted in significant loss of the poison, while centrifugation

                        ‘Estimates of a fatal dose of cyanide for a human range from about l(l to 200 milligrams,     depending
                        on the person’s age and weight.




                        Page 13                                 GAOiHRD-90-164     FDA’s Actions   on Poisoned      Chilean   Fruit
                            Appendix I
                            FDA’s Laboratory Testing and Sample
                            Protection Were Appropriate




                            resulted in less cyanide being lost. Accordingly, the FDA analyst cen-
                            trifuged the grapes to remove the grape particles rather than risk losing
                            the cyanide from the small sample of two grapes through distillation. A
                            subsequent FLNlaboratory experiment confirmed that using a centrifuge
                            was an acceptable method to prepare fruit samples for chloramine-T
                            analysis. In our view, the modification was appropriate, did not distort
                            the test results, and yielded a valid finding that the sampled grapes con-
                            tained cyanide.


Test Results Were           FDA  procedures require that laboratory worksheets be completed as tests
                            are performed. For this case, the FDAanalysts who performed the tests
Promptly Recorded           completed the worksheets on March 15,1989,3 days after performing
                            the tests on the sample found to contain cyanide. FDA officials said that
                            the worksheets were not completed sooner because the analysts con-
                            tinued to perform tests on additional fruit samples from the same crate
                            that contained the poisoned grapes. Our review of the worksheets con-
                            firmed these statements.

                            In our view, the 3-day delay in completing the worksheets did not invali-
                            date the test results because other evidentiary documents were main-
                            tained by FDA and recorded immediately. Portions of the laboratory
                            worksheets and other records that were prepared on March 12,1989,
                            the same date the poisoned grapes were found, support FDA'S finding of
                            cyanide. These documents included:

                        l   a log of cyantesmo test results, which included an entry noting the posi-
                            tive cyanide finding;
                        l   a photograph of the first cyantesmo paper strip, which had been placed
                            in a laboratory flask with the sample and which showed a positive reac-
                            tion to cyanide;
                        l   two cyantesmo paper strips showing a color change (indicating cyanide)
                            mounted on a laboratory worksheet; and
                        l   the chloramine-T test graph produced by the spectrophotometer and the
                            worksheet prepared by the analyst who performed the test.


                            FDA'S laboratory procedures manual establishes requirements for pro-
Sample Accountability       tecting and maintaining proper accountability for samples of domestic
and Protection Were         food products. Among other things, the manual requires that all samples
Adequate                    taken for examination be individually marked and transfers of the sam-
                            ples be recorded. The manual does not specify that the same procedures
                            are to be used for import samples, but it does require that the laboratory


                            Page 14                               GAO/HRIHO-164   FDA’s Actions   on Poisoned Chilean   Fruit
    Appendix I
    FDA’s Laboratory Testing and Sample
    Protection Were Appropriate




    performing the analysis establish a written procedure to account for
    import sample integrity and continuity of handling.

    The Philadelphia laboratory’s written procedures to account for and
    protect import samples are similar to FDA'S requirements for domestic
    foods. The procedure for inscribing identifying marks on crates of
    inspected fruit was modified slightly in the case of the Chilean fruit
    imports; however, adequate accountability and protection was main-
    tained over fruit that was inspected and tested. We were able to track
    the sample that subsequently tested positive for cyanide from the time
    it was assigned a sample number at the dock in Philadelphia until it
    arrived at the FDA laboratory. We did not find any serious deficiencies in
    the chain of custody for the sample at various points in the process. The
    FBI also looked at this process and found the chain of custody to be ade-
    quate to protect the integrity of the sample.

    FDA  visually examined about 1,200 crates of fruit from the Almeria Star
    on March 11 and 12, 1989. FDA'S Philadelphia district director said that
    because the inspectors were examining many crates FDA did not mark
    each crate examined as provided for in its procedures. Instead, if an
    inspector found fruit that appeared unusual, the procedure was to take
    the entire crate to an inspection table, leaving the suspicious-looking
    fruit on top. Another inspector was responsible for placing the fruit in a
    plastic bag and assigning a sample number both to the suspicious fruit
    and the crate from which it came. Periodically, another FDA employee
    transported the collected samples to FDA'S Philadelphia laboratory. The
    laboratory maintained a log of samples sent from the dock and entered
    the chemical test results in the log. In our view, the modification to the
    crate-marking procedure had no effect on the validity of the cyanide
    finding or the origin of the poisoned grapes, because only Chilean fruit
    from the Almeria Star was being inspected at the time of the cyanide
    discovery.

    We also assessed the adequacy of the chain of custody for the sample of
    grapes that tested positive for cyanide. We were able to trace the cus-
    tody of the sample from the point FDA assigned it a sample number at
    the dock all the way through the testing process. Among other things,
    FDA documents identified:

. the FDA staff who assigned the sample number and who transferred                                the
    sample from the dock to FDA'S Philadelphia laboratory;
l   the FDA analysts who performed the laboratory tests; and



    Page 15                               GAO/HRD!3O-1f34   FDA’s Actions   on Poisoned Chilean   Fruit
                           Appendix I
                           FDA’s Laboratory Testing and Sample
                           Protection Were Appropriate




                       l   the FDA representative who took a portion of the sample of the contami-
                           nated grapes to FDA'S Elemental Analysis Research Center in Cincinnati,
                           Ohio, for further analysis.3

                           FDA'sPhiladelphia laboratory had retained, as of June 1990, part of the
                           sample of grapes used in the chloramine-T test.

                           The FBI told us that it was also able to reconstruct the custody of the
                           sample when it conducted its investigation into the incident, and found
                           it to be adequate.


                           Since the March 1989 finding of cyanide in Chilean grapes, FDA and
Studies Show Cyanide       other researchers have conducted several studies on the effects of cya-
Can Be Injected Into       nide on fruit. The objectives were to determine (1) whether cyanide can
Fruit and Retained         be injected into grapes and other fruit, (2) the amount that can be
                           injected, and (3) the extent to which fruit can retain cyanide over time.
                           Some studies also observed whether and to what extent fruit containing
                           cyanide changed appearance over time.

                           Although the studies’ methodologies and results differ significantly,
                           they all showed that grapes and other fruit can be injected with cyanide.
                           When analyzed over time periods ranging from 4 hours to 16 days after
                           injection, grapes showed retention levels of cyanide ranging from less
                           than 1 percent to over 9 percent of the quantity of cyanide injected,
                           However, there was no clear relationship between the amount of cya-
                           nide injected and the percentage of cyanide retained nor with the time
                           periods when the analysis was conducted. The studies showed that some
                           fruit injected with lesser amounts of cyanide retained more cyanide
                           after a given period of time than the same type of fruit injected with
                           larger amounts of cyanide. The studies also showed that some grapes
                           and other fruit appeared normal for 2 weeks or more after injection
                           before they began to change color, form, or texture. Key findings of
                           some of the studies follow.




                           “This center specializes in forensic analysis of several different   kinds of products regulated by FDA,
                           including foods.




                           Page 16                                   GAO/HRMJO-164        FDA’s Actions   on Poisoned Chilean   Fruit
    Appendix I
    FM’s Laboratmy   Testing and !hmple
    Protection Were Appropriate




l   Studies performed by FDA’S Center for Food Safety and Applied Nutri-
    tion and FDA'S Elemental Analysis Research Center showed that some
    poisoned fruit, when refrigerated, retained cyanide at levels comparable
    to those found in the grapes tested by FDA’S Philadelphia laboratory.
    Some fruit also retained their normal appearance for up to 16 days.
    (Fruit on the Almeria Star was refrigerated during its 13-day voyage to
    Philadelphia.)
l   A 1989 study performed at the University of Chile indicated that the
    same variety of grapes found contaminated in Philadelphia, when
    refrigerated, generally retained a fresh-looking appearance for at least 2
    weeks after a 50-milligram injection of cyanide per grape. Other fruit
    also appeared normal for extended periods after being poisoned with
    large amounts of cyanide. However, the study makes no mention of the
    amounts or percentages of cyanide the fruit retained.
l   A study by other Chilean researchers on the retention rates of cyanide
    concluded that because cyanide naturally dissipates rapidly from grapes
    after injection, the contaminated grapes found in Philadelphia almost
    certainly must have been injected not more than 4 hours before FDA'S
    tests. This study was done on grapes that were not refrigerated. How-
    ever, a study conducted by the University of California at Davis for the
    Chilean Exporters Association contradicts this theory. Although the
    second study’s focus was on whether cyanide could migrate from
     injected grapes to neighboring ones, the reported results indicate that
     grapes that absorbed cyanide through migration retained the cyanide
     for as long as 21 days, The study did not indicate whether or not the
     grapes injected with cyanide were refrigerated.




     Page 17                              GAO/HRLMO-164   FDA’s Actions   on Poisoned   Chilean   Fruit
Al)~~~llx: 11
--

FDA’s Actions Consistent With Law
and Regulations

                        The Federal Food, Drug, and Cosmetic Act provides the basic statutory
                        authority governing the treatment of imported food products. FDA'S poli-
                        cies for dealing with product tampering are specified in its Regulatory
                        Procedures Manual. FDA'S actions to (1) temporarily suspend Chilean
                        fruit imports, (2) issue a public health warning, (3) deny entry to the
                        fruit on the Almeria Star, and (4) conduct increased inspections of
                        Chilean fruit imports were consistent with FDA'S statutory authority and
                        regulations. In addition, FDA's actions were consistent with the actions it
                        has taken on other incidents involving tampering threats against
                        imported foods.

                        Based on its legal authority, its experience with tampering incidents,
                        results of its laboratory testing, and experimental data showing that
                        fruit could be injected with cyanide and appear normal for certain
                        periods, FDA had adequate justification for the actions it took regarding
                        Chilean fruit.


                        Section 801 of the Federal Food, Drug, and Cosmetic Act provides that
Law Prohibits           imported food products that appear to be adulterated are to be denied
Poisoned Food From      entry into the United States. A product is adulterated if it contains an
Entering the United     added poisonous substance that may render it harmful to health. For
                        imported food, the owner of a product that appears to be adulterated
States                  has three options: destroy the product, remove it from the United States,
                        or bring it into compliance with the law. In an instance of cyanide
                        poisoning, the product cannot be brought into compliance; thus, it must
                        be destroyed or shipped out of the United States.

                        Under section 705 of the act, FDA can disseminate information on foods
                        that pose an imminent danger to public health. FDA'S Regulatory Proce-
                        dures Manual is consistent with the act and includes requirements for
                        (1) investigating tampering threats or incidents, (2) notifying state and
                        foreign governments when FDA has found an adulterated product, and
                        (3) instituting product recalls or market withdrawals of adulterated
                        foods. The manual also requires FDA to evaluate the potential health
                        hazard caused by a tampering threat or incident.

                        Once FDA determined that some fruit on the Almeria Star contained cya-
                        nide, FDA:

                      0 refused to admit any of the ship’s fruit. FDA did this because (1) tam-
                        pering was the only possible explanation for the presence of cyanide in
                        the fruit and (2) other fruits may have been poisoned but might not


                        Page 18                      GAO/HRDW164   FDA’s Actions   on Poisoned   Chilean   Fruit
                        AppendixIl
                        FIN’s Actions Consistent   With Law
                        and Regulations




                        have been detectable without laboratory analysis of all the fruit, which
                        would have destroyed it;
                    l   notified state health departments and other countries that also imported
                        Chilean fruit (including Canada, Japan, and European countries) of the
                        cyanide finding;
                    l   recommended that U.S. retail outlets remove Chilean fruit from distribu-
                        tion and that consumers refrain from eating Chilean fruit they had
                        purchased;
                    l   increased inspections of incoming Chilean fruit and fruit in cold storage
                        warehouses; and
                    l   prepared a health hazard evaluation report. The March 1989 report
                        noted that FDA tests showed enough cyanide could be injected into fruit
                        to cause injury or death. Because the incident involved deliberate tam-
                        pering rather than accidental adulteration, the report concluded that FDA
                        could not estimate with any degree of certainty the chances that other
                        shipments might also have been tampered with.

                        In sum, the actions FDA took subsequent to discovering cyanide in a
                        sample of Chilean fruit were consistent with its statutory authority and
                        procedures for dealing with imported foods that appear to be
                        adulterated.


                        Between 1984 and 1989, FDA investigated about 3,800 tampering threats
FDA’s Actions           and incidents. FDA officials said that the Chilean fruit incident was the
Consistent With         largest tampering incident FDA has investigated because the threat did
Actions Taken in        not specify the type(s) of fruit poisoned or the vessel(s) on which the
                        fruit was being shipped, as had been done in some other tampering inci-
Similar Incidents       dents. It was also the first occasion that FDA found an imported food
                        product that had been tampered with actually arriving in the United
                        States. Thus, FDA had no exact precedent to guide its investigation of
                        this incident. However, FDA'S actions on the Chilean fruit were consistent
                        with its actions on two earlier tampering incidents.

                        One 1985 incident involved tea. An unknown person sent a letter to the
                        U.S. Embassy in Sri Lanka claiming that tea bound for the United States
                        had been poisoned with cyanide. Similar to its actions on Chilean fruit,
                        FDA (1) refused entry of Sri Lankan tea into the United States, (2) devel-
                        oped a test to detect cyanide in tea, and (3) increased its examinations of
                        Sri Lankan tea for cyanide. After receiving no additional threats nor
                        finding cyanide in tea that was sampled, FDA lifted its ban on Sri Lankan
                        tea imports 4 months after denying entry.



                        Page19                                GAO/HRD-SO-164   FDA’s Actions   on Poisoned   Chilean   Fruit
Appendix 11
FDA’s Actions Consistent   With Law
and Regulations




The second incident occurred in 1978 when terrorists contaminated with
metallic mercury a shipment of Israeli oranges bound for Germany and
the United States. Oranges unloaded in Germany were found to contain
mercury. When the remainder of the shipment arrived in the United
States, FDA performed visual examinations and conducted other tests on
77,000 oranges. FDA did not find mercury in any of the inspected
oranges. After detaining the shipment for 4 days, while tests were being
conducted, FDA released it for distribution to markets.




 Page 20                              GAO/HRMJO-164   FDA’s Actions   on Poisoned   Chilean   J?ruit
Appendix III

FDA Consulted With Others Before Acting


                    The Federal Food, Drug, and Cosmetic Act does not require FDA to con-
                    sult with other federal agencies in determining that an imported food
                    product appears to be adulterated and, thus, poses an imminent danger
                    to health. Nor does the act require FDA to consult with other agencies on
                    how to remedy the problem.

                    Nevertheless, after determining that Chilean fruit aboard the Almeria
                    Star was adulterated, FDA consulted with several federal agencies
                    regarding proposals to confront the danger. Before taking action on
                    March 13, 1989, the FDA Commissioner contacted the Secretary of Health
                    and Human Services and the Office of the President on the proposed
                    actions. Both HHS and the Office of the President supported the Commis-
                    sioner’s proposals. Additionally, FDA consulted with the Departments of
                    State and Agriculture and the Customs Service. Because FDA is the pri-
                    mary public health agency for dealing with these situations, these agen-
                    cies deferred any decisions regarding the fruit to FDA and made no
                    recommendations to FDA for dealing with the tampering incident.


                    Additionally, FDA consulted with the Chilean Foreign and Agricultural
U.S. Agencies       Ministers, the Chilean Ambassador, and representatives of the Chilean
Consulted With      Exporters Association and the American Produce Association. The main
Chilean Interests   focus of these consultations was to devise an inspection plan for Chilean
                    fruit and release any fruit that passed inspection. The Chilean repre-
                    sentatives made recommendations to FDA concerning the proposed plan.
                    They recommended that FDA examine 1 to 2 percent of the shipments
                    because of the time and expense of performing more extensive examina-
                    tions. However, FDA believed this inspection level was too low. FDA'S sta-
                    tistical calculations showed that a lo-percent inspection level was
                    necessary to provide a sufficient level of confidence that any additional
                    tainted fruit would be found.

                    The State Department helped to convince the Chilean representatives of
                    the need to inspect more fruit than what Chile proposed. Ultimately, FDA
                    and the Chilean government agreed on a 5-percent inspection level for
                    incoming fruit and fruit in storage. This level was based on the time and
                    cost of performing inspections and the ability to inspect, store, and
                    transport incoming fruit and fruit already in cold storage waiting to be
                    inspected.’ FDA concluded that this level of inspection would be suffi-
                    cient to detect contaminated fruit because of the other actions it had

                    ‘FDA had used about 100 staff days over a 4-day period to inspect slightly more than 3 percent of the
                    fruit on the Almeria Star.




                    Page 21                                GAO/HRD-9@164      FDA’s Actions   on Poisoned   Chilean   Fruit
-
    Appendix III                                                                                 r
    FDA Consulted   With Others Before   Acting




    taken to safeguard consumers, including denying entry to fruit on the
    Almeria Star and recommending the removal of Chilean fruit from retail
    outlets. The Chilean government also agreed to provide additional
    security and perform fruit inspections in Chile.




    Page 22                               GAO/HRD9@164   FDA’s Actions   on Poisoned   Chilean   Fruit
Chronology of Events Relating to Poisoning of
Chilean Fruit

                    This chronology details the key events during the course of the Chilean
                    fruit tampering incident. For discussion purposes, we have organized
                    the chronology by the time periods during which key decisions were
                    made.


                    On March 2, 1989, an unidentified person called the U.S. Embassy in
March 2 to 7,1989   Santiago, Chile, claiming to have injected cyanide into fruit destined for
                    the United States and Japan. The caller said that his purpose was to
                    draw attention to the poor living conditions of Chilean workers. The U.S.
                    Embassy notified the Department of State of the threat. The State
                    Department then notified the Customs Service, which in turn notified
                    FDA.


                    Customs ordinarily clears Chilean fruit for entry into the United States
                    in advance of its arrival and does not detain it at the port of entry for
                    inspection. Although the Department of State thought the threat was a
                    hoax, the Customs Service, as a precaution, placed a temporary hold at
                    ports of entry on new arrivals of Chilean fruit shipments on March 3
                    and notified FDA of its action. As the threat posed a potential public
                    health problem, FDA took lead responsibility for the investigation based
                    on the provisions of the Federal Food, Drug, and Cosmetic Act and an
                    agreement with Customs. After meeting with representatives of the
                    Chilean government and the Chilean fruit industry, FDA concluded that
                    the threat was a hoax and, on March 6, requested Customs to lift the
                    hold on most Chilean fruit imports. As a precaution, on March 6, FDA
                    also began to visually examine 10 percent of large Chilean fruit. On
                    March 7, FDA began conducting laboratory experiments on the feasibility
                    and effects of poisoning fruit with cyanide.


                    On March 8, 1989, the U.S. Embassy in Chile received a second tele-
March 8 to 10       phone call that essentially repeated the first threat and insisted that the
                    threat was not a hoax. On March 9, the State Department notified FDA of
                    the second threat. Although the Department believed this threat was
                    also a hoax, as a precaution, FDA, on March 10, decided to visually
                    inspect 1 to 2 percent of all Chilean fruit imports. U.S. Department of
                    Agriculture personnel who examine and grade the quality of incoming
                    fruit provided guidance to FDA inspectors on the types of defects that
                    were normal in fruit (such as staple or nail holes and blemishes).




                    Page 23                      GAO/HRLHO-164   FDA’s Actions   on Poisoned   Chilean   Fruit
                  Appendix TV
                  Chronology of Events Relating   to Poisoning
                  of CNean Fruit




                  On the morning of March 11, 1989, the vessel Almeria Star arrived in
March 11 to 1’7   Philadelphia. This was the first ship containing Chilean fruit to arrive in
                  the United States subsequent to FDA'S decision to visually examine 1 to 2
                  percent of the fruit. FDA began inspecting the fruit on Almeria Star on
                  March 11. Allegations were made that FDA targeted the Almeria Star to
                  the exclusion of other arriving vessels containing Chilean fruit, implying
                  that FDA had been “tipped” as to where the poisoned fruit could be
                  found. However, we found no evidence to support this allegation. On
                  March 10,1989, two other ships carrying Chilean fruit had arrived in
                  Philadelphia and Los Angeles before FDAdecided to inspect all Chilean
                  fruit. FDA subsequently examined about 4 to 5 percent of the fruit from
                  those ships that was being held in cold storage warehouses. None of the
                  fruit examined from these two ships contained cyanide, and FDA released
                  the fruit for distribution.

                  The inspection of fruit from the Almeria Star consisted of FDA inspectors
                  judgmentally selecting pallets of fruit from different growers and ship-
                  pers. Each pallet contained approximately 100 crates of fruit. Under
                  this procedure, once a pallet was selected, inspectors examined every
                  piece of fruit in every crate from the pallet. Fruit with abnormalities,
                   such as softness or an apparent injection mark, was sent to FDA's Phila-
                   delphia laboratory for analysis. By March 12, FDA inspectors had visu-
                   ally examined about 1,200 crates of fruit (less than 1 percent of the
                   cargo) and FDA's Philadelphia laboratory had analyzed about 75 suspi-
                   cious-looking samples; one of the samples, consisting of two grapes,
                   tested positive for cyanide. Upon analysis, FDA found the grapes con-
                   tained about 0.003 milligrams of cyanide.

                  FDA's  Philadelphia district office immediately notified FDA headquarters
                  of the positive cyanide finding. After the FDA Commissioner was notified
                  by FDA headquarters, on March 13, he interviewed the FDA chemists who
                  performed the tests regarding the testing methodology and results. The
                  Commissioner interviewed the chemists to satisfy himself that the
                  testing had been performed properly. He also obtained the preliminary
                  results of FDA'S laboratory experiments, which showed that some fruits
                  injected with cyanide retained the poison and still appeared edible sev-
                  eral days later. Based on this evidence and after consultation with HHS,
                  the Commissioner requested Customs to temporarily suspend all Chilean
                  fruit imports. In addition, the Commissioner recommended the removal
                  and destruction of all Chilean fruit in retail outlets because of the
                  impracticality of attempting to inspect the large volume of fruit already
                  in the distribution chain. The Commissioner also warned consumers not
                  to eat any Chilean fruit they had purchased. FDA was concerned that


                  Page 24                               GAO/HRD-!jO-164   FDA’s Actions   on Poisoned   Chilean   Fruit
                       Appendix IV
                       Chronology of Events Relating   to Poisoning
                       of Chilean Fruit




                       more fruit from the Almeria Star might be contaminated but escape FDA
                       detection. Because of this and the impracticality of inspecting the entire
                       cargo of approximately 365,000 crates of fruit, FDA denied entry to the
                       entire shipment of fruit on that vessel.

                       FDA  then began to work with representatives of several federal agencies,
                       including other components of the Department of Health and Human
                       Services, State, and representatives of the Chilean government and the
                       fruit industry to develop a plan to inspect Chilean fruit. The former FDA
                       Commissioner told us that FDA’sstrategy in developing the inspection
                       plan was to return Chilean fruit that passed inspection to the market as
                       rapidly as possible. On March 17, FDA announced its inspection plan. The
                       plan called for different inspection levels based on when the fruit was
                       shipped to the United States. Under the plan, industry-hired inspectors
                       under FDA supervision would examine 1 percent of fruit shipments made
                       on or before February 20, 1989. Shipments made after that date would
                       be inspected at a 5-percent level. Additionally, security and inspection
                       levels in Chile would be increased.

                       Also, on March 17, FDA was notified that a third telephone threat had
                       been received by the U.S. Embassy in Chile.


                       During this period, industry inspectors continued to examine arriving
March 18 to April 14   Chilean fruit shipments and fruit still in warehouses. About 650 tempo-
                       rary workers hired by industry performed the inspections. Since no fur-
                       ther cyanide contamination was found, by March 29, FDA began to
                       reduce the inspection levels. By April 14, FDA discontinued the increased
                       inspection program.




                       Page 26                               GAO/HRD9@164 FDA's Actions on Poisoned Chilean Fruit
Review of FDA Testing Procedures Used
to Determine Cyanide in Chilean
Fruit-Consultants’ Report to GAO
                    Fred R. Albright, Director, Health Services Division, Lancaster Laborato-
Consultants         ries, Lancaster, Pennsylvania

                    Janet Fleming, Division of Consolidated Laboratory Services, Virginia
                    Department of General Services, Richmond, Virginia

                    James F. Lawrence, Health Protection Branch, Health and Welfare
                    Canada, Ottawa, Canada

                    Paul Mason, Division of Consolidated Laboratory Services, Virginia
                    Department of General Services, Richmond, Virginia


                    Listed below are the questions we asked the consultants to address. The
Questions GAO       consultants report on their findings follows.
Furnished to Four
                    I. Did         Use Generally Accepted Tests to Detect Cyanide?
Consultants                  FDA


                    FDA’SPhiladelphia laboratory used cyantesmo and chloramine-T tests to
                    detect the presence of cyanide in Chilean grapes and other fruit. As we
                    understand, the specially treated paper used in the cyantesmo test
                    changes color when acid is added to a sample containing cyanide. The
                    chloramine-T test uses a spectrophotometer to quantify the amount of
                    cyanide in a liquid by measuring the intensity of the liquid’s color.

                    (1) Are these two tests generally considered by experts to be acceptable
                    screening methods to detect cyanide?

                    (2) Are there any other tests or other methods that would have pro-
                    duced more reliable results or been more appropriate to use in a situa-
                    tion such as this one? If so, please describe these methods and the
                    advantages over the tests FDAused.

                    In regard to the cyantesmo test that     FDA    used to initially screen fruit:

                    (1) Would the cyantesmo test detect any poison or harmful substance
                    other than cyanide?

                    (2) Would the presence of other substances, whether harmful or not,
                    produce a reaction that could cause the cyantesmo paper to change color
                    and possibly distort the test results (i.e., produce a false positive)?




                    Page 26                         GAO/HRDSO-164    FDA’s Actions   on Poisoned   Chilean   Fruit
    APpendirV
    Review of FDA Testing Procedures Used
    to Determine Cyanide in Chilean
    Frult-thumltants’    Beport to GAO




    (3) Conversely, could other substances make the cyantesmo paper less
    likely to change color (i.e., produce a false negative)?

    (4) Would sulfite, which was used in the packing in the Chilean fruit
    crates, affect the cyantesmo test? (See section on “Effect of Sulfite on
    Cyantesmo Paper” in FDA'S Laboratory Information Bulletin (LIB) 3352
    which is included with the enclosures.)

    m’s Laboratory Information Bulletins 3029,3352, and 3383, (enclosed)
    describe procedures used by FDAlaboratories for conducting chloramine-
    T tests in tea, use of cyantesmo paper to detect cyanide in fruit, and the
    extraction of cyanide from fruit. These bulletins are disseminated to
    FDA’sfield laboratories for consideration in future testing.

    (1) Are these procedures reasonable or appropriate? If not, please
    describe the proper methods for conducting the tests versus the methods
    described by FDA.

    F’LN’SLIB 3029 describes a chloramine-T test to detect cyanide in tea
    that used a distillation method. In the grape incident, the FDAanalyst
    substituted centrifuging for distillation. According to FIM, both methods
    provide accurate test results, but the centrifuging method is quicker.

    (1) Is it appropriate or reasonable to substitute centrifuging for distilla-
    tion when conducting chloramineT tests? If not, please explain why it is
    not and the extent, if any, centrifuging affects the chloramine-T test
    results?

    II. Did m Pronerlv Conduct the Testing and Correctlv Analyze the
    Results?

    FDA  believes that the cyantesmo and chloramine-T tests and analysis
    performed by its Philadelphia laboratory were done in accordance with
    established scientific principles and standards. However, other chemists
    cited in news stories contend that FDA's work was seriously flawed. Spe-
    cifically, the critics have cited the following as problems with the FDA
    tests:

.   FDA did not retain part of the samples for future analysis;
.   FDA improperly modified the chloramine-T test procedure by using the
    centrifuge instead of distillation;
l   The cyantesmo test is not conclusive and only indicates the possibility of
    the presence of cyanide or other contaminants;


    Page 27                            GAO/EED90164   FDA’s Actiona   on Poisoned   Chilean   Fhit
                      Revlew of FJM Testing Prmedm     Used
                      to Determine Cyanide in Chilean
                      Fmlt-Conanltanta’    Report to GAO




                  . The chloramine-T test indicated such a low level of cyanide present that
                    it was inconclusive;
                  l FDA’stest overstated the amount of cyanide present (the chloramine-T
                    test should have shown 0.28 ppm of cyanide present in the grapes, com-
                    pared to FDA's 0.51 ppm result); and,
                  . The grapes may have been contaminated accidentally in the FDA lab,
                    based on calculations done by the University of California after injecting
                    160 micrograms of cyanide into a grape and then conducting a chlora-
                    mine-T test.

                      (1) Are the criticisms of IDA’S testing valid?. If the criticisms are legiti-
                      mate, describe the impact of any testing deficiencies on FBA’Stests of
                      Chilean fruit.

                      Considering your overall assessment of FDA'S testing of the Chilean fruit,
                      do you believe there were any deficiencies in the testing that could have
                      materially affected the outcome?

                      III. Was FDA's Research on Contamination of Fruit With Cyanide Con-
                      ducted in Accordance With Appropriate Scientific Principles?

                      FDA's Center for Food Safety and Applied Nutrition    conducted labora-
                      tory studies in March and April 1989 on the effects of contaminating
                      fruit with cyanide. The purpose of this research was to determine (1)
                      whether fruit would retain cyanide after it is injected, (2) how cyanide
                      affected the appearance of the fruit, (3) how rapidly the cyanide dissi-
                      pated, and (4) whether existing methods to detect cyanide were reliable.

                      (1) To what extent did FDA'S research results serve as a valid indicator
                      of the effects of cyanide on fruit?


                      The prime task of the consultants was to assess whether the FDAused
1. Introduction       appropriate analytical procedures in testing cyanide-contaminated
                      Chilean fruit. The GAO provided a list of questions which were to be spe-
                      cifically addressed by the consultants and included in their report.
                      Although the consultant team was assembled primarily to evaluate ana-
                      lytical chemical procedures used by FDA,it was also asked by the GAO to
                      comment on sampling procedures, documentation and any other matters
                      that may have influenced the analytical results obtained by FDA. The
                      consultants did not address the issue of criminal tampering of the
                      grapes. This report contains the findings of the consultant team and rep-
                      resents their unanimous opinion.


                       Page 28                           GAO/‘EIRD-ml64   FDA’s Actions   on Poisoned   Chilean   Fruit
                           Appendix V
                           Revlew of FM Testing Procedures   Used
                           to Jh%mnine Cyanide in Chilean
                           Fruit-ConsultantiReporttiGAO




                           The GAO sent to each consultant a file containing substantial background
2. Procedure               material relating to all aspects of the cyanide-Chilean fruit incident.
                           This included detailed copies of F’IManalytical results, descriptions of
                           testing procedures, supplementary studies by FW’S Center for Food
                           Safety and Applied Nutrition (CFSAN) and press articles related to the
                           incident.

                           Each consultant independently reviewed the information, then met in
                           Philadelphia on 13 and 14 February 1990 with GAO project evaluators
                           and FDA-Philadelphia personnel. On 13 February 1990, the consultants
                           were fully briefed by GAO evaluators on all aspects of the cyanide-
                           Chilean fruit incident and were given additional documents to consider
                           as part of the evaluation. On 14 February 1990, the consultants inter-
                           viewed Fn-+Philadelphia staff (and F. Fricke, FDA,Cincinnati) who were
                           directly involved in the analysis of Chilean fruit for cyanide.



3. Findings

Part A. Responses to GAO   I. Did FDA Use Generally Accepted Tests to Detect Cyanide?
Questions                  A. The consultants agreed that the m did use generally accepted chem-
                           ical tests to detect cyanide in fruit. Thetwo tests used by FDA, namely
                           the cyantesmo strip and the chloramine-T spectrophotometric method
                           are based on classical chemical reactions. The cyantesmo strip test is
                           based on the reaction of hydrogen cyanide gas (HCN) (generated by acidi-
                           fication of the sample) with iron salts impregnated in a paper strip to
                           form a blue complex, Prussian Blue. Analytical applications of this reac-
                           tion date back to at least 1947 (A.O. Gettler and L. Goldbaum, Anal.
                           Chem. 19, 270 (1947)). The reaction is very selective for HCN. Reducing
                           agents may interfere by causing a reduced response to HCN, possibly
                           leading to false negatives if the CN levels were close to the detection
                           limit. Sulfite, as SO,, for example, was shown by FDA to cause a reduced
                           response to HCN. Halides such as chloride, bromide and iodide do not
                           interfere. Thiocyanate (XX), another type of cyanide does not produce a
                           response because it is not volatile upon acidification.

                           The chloramine-T test involves a series of chemical reactions with cya-
                           nide (CN) in solution to yield a magenta (purplish-red) colored dye. Cya-
                           nide first reacts with chloramine-T to produce cyanogen chloride which
                           in turn reacts with pyridine to yield a dialdehyde. The dialdehyde reacts


                           Page 29                            GAO/HI?D9@184   FDA’s Actions   on Poisoned   Chilean Fruit
-
    Appendix V
    Review of PLM Testing Procedures Used
    to Determine Cyanide in Chilean
    Fruit-Coneultanta    Report to GAO




    with barbituric acid to produce the magenta colored polymethine dye.
    This product absorbs light at a specific wavelength in the visible spec-
    trum. The color (visible absorption) of the final solution is measured
    using a calorimeter or spectrophotometer. Analytical applications of this
    reaction date back to at least 1947 (J. Epstein, Anal. Chem. 19, 273
    (1947)). This reaction is also rather selective. However, nitrz at 25
    parts per million or greater may lead to a slight increase in intensity of
    the color formed and might even yield a false positive if present in very
    large concentrations. Also, thiocyanate reacts in a similar manner as CN.
    Reducing agents, particularly sulfite, may cause a reduction in color for-
    mation. This could lead to false negatives if CN levels were near the
    detection limit and sulfite (for example) levels were high enough. (J.C.L.
    Meeussen, E.J.M. Temminghoff, M.G. Keizer and I. Novozamsky, Analyst
    114,959 (1989)). Variations of the chloramine-T method have been used
    successfully to determine CN in soybean products, cassava, industrial
    waste waters, milk or blood at sub- parts per million concentrations.

    The consultants are of the opinion that the reactions involved in both
    the cyantesmo test and the chloramine-T spectrophotometric method are
    well known and have been used successfully for a variety of sample
    types over many years. In applying any analytical procedure to a new
    sample type, it is imperative to analyze reagent blanks, sample blanks,
    standard CN solutions and spiked blanks (sample and reagent blanks
    with known amounts of CN added). These analyses are required to deter-
    mine possible interferences, both positive and negative, as well as detec-
    tion limits and linear range if quantitation is required. Both of these
    tests are considered acceptable for screening fruit provided that blanks
    and spikes are regularly analyzed as mentioned above. The information
    provided to the consultants clearly indicated that the FDA carried out all
    necessary method tests before and during the application of the proce-
    dures to grapes.

    Other calorimetric tests for CN (picric acid, phenophthalein, copper
    acetoacetate) may have worked as well as those used by FDA, but they
    offer no particular advantages. Methods involving specific ion elec-
    trodes, gas chromatography-mass spectrometry, flow injection analysis,
    titration or ion chromatography all require more sample preparation or
    specialized equipment. In addition, the reliability of the newer methods
    has not been fully evaluated.




     Page 30                           GAO/HRD-!%164   FDA’s Actions   on Poisoned   Chilean   Fruit
Appendix V
Review of FBA Testing Procedures Used
to Determine Cyanide in Chilean
Fruit-Ckmmltanta’    Report to GAO




B. Use of the Cvantesmo Test for Screening Fruit

(1) As far as the consultants are aware, from the literature and from
personal experience (J. Fleming, consultant) no other known poison
gives a positive result with the cyantesmo test as employed by the FDA.

(2) There are no known substances (especially in grapes) which would
yield a false positive CN value with the cyantesmo test as employed by
the FDA. Because the test strip does not come into direct contact with the
acidified sample in the flask, non-volatile anions such as thiocyanate
and nitrate which might yield a positive value if the test strip were actu-
ally immersed in the sample liquid, do not interfere.

Independent experience by the Virginia Division of Consolidated Labo-
ratory Services confirms the appropriateness of the cyantesmo test.
After accounts of the cyanide-Chilean fruit incident were reported by
the news media, Virginia Department of Agriculture received a com-
plaint about grapes that had made a consumer sick. Inspectors followed
up on this complaint and collected white and red Chilean grapes from
complainant’s grocery store. Approximately 3 pounds of red grapes and
approximately 3.5 pounds of white grapes were submitted to Consoli-
dated Labs for tampering analyses on March 16,1989. Janet Fleming,
consultant, independently analyzed these grapes by a very similar
method to FDA'S. Each grape was visually examined and any suspicious
grapes were microscopically examined. One red grape and one white
grape each had a slight puncture mark. Both were crushed and screened
for cyanide by cyantesmo strips and were found to be negative. Along
with the suspect grapes, control (normal) white and red grapes and
spiked grapes at 2 and 3 parts per million cyanide levels were also
tested. Control grapes were negative and spiked grapes tested positive.
Virginia has utilized these same screening procedures (visual, micro-
scopic and cyantesmo) for suspected food tampering cases for several
years and has found these to be appropriate.

(3) It has been shown in the literature and from FDA studies that sulfite
(as SO,) clearly can have a negative effect on CN detection with several
types of calorimetric CNtests. Most other substances that have been
shown to interfere, do so only to a lesser extent and then only in solu-
tion There are no reports in the literature on volatiles other than SO,
that would cause false negatives in the test as performed by the FDA.




Page 31                           GAO/HRD9O-164   FM’s   Actions   on Poisoned   Chilean   Fruit
-
     Appendix V
     Review of FDA Testing Procedures Used
     to Determine Cyanide in Chilean
     Fruit-Consultants’   Report to GAO




-.
     (4) Sulfite has been shown in the literature to be one of the major
     interferants in the calorimetric determination of CN by either the Prus-
     sian Blue (cyantesmo test strip) or chloramine-T reaction. Its effect is to
     inhibit color formation in both tests which could lead to false negatives.
     The FDA studies on the effect of sulfite on the cyantesmo test clearly
     showed that sulfite at the maximum permitted level on grapes, 10 parts
     per million, could have a negative effect on results at 1 parts per million
     CK or less. If sulfite were present in the grape sample that was found to
     be positive, the true value for CN would likely have been higher than
     that estimated by the tests used by FDA. The procedures used in the sul-
     fite studies carried out by FDA conform to standard analytical practices
     (i.e. analyzing samples with and without sulfite at different concentra-
     tion levels and observing the effects on CN determination). The FDA did
     not test for sulfite in the bunch of grapes associated with the two posi-
     tive grapes. It is conceivable that very low levels of cn’ were present
     from migration but may not have been detectable if sulfite were present.

     C. Comments on FDA Laboratory Information Bulletins 3029, 3352 and
     3383

     The FDA Laboratory Information Bulletin 3029 describes a calorimetric
     procedure using chloramine-T for the determination of CN in tea. The FDA
     modified this procedure for the determination of CN in grapes. The major
     change was to omit the distillation step used for tea and, instead, to cen-
     trifuge the samples to remove suspended matter so that a portion of the
     clear liquid could be tested using the chloramine-T reaction. The consul-
     tants have no difficulty in accepting this change. Modifications of
     methods for specific applications is commonplace in analytical chem-
     istry and is done for a variety of reasons. However, with any modifica-
     tion or application of an existing method to a new type of sample (eg.
     grapes instead of tea) an evaluation must be performed to prove that
     the modifications are acceptable for that particular analysis. The FDA
     used an accepted analytical approach and showed that omission of the
     distillation step had no effect on the determination of CN in grapes at
     levels greater than ca 0.2 parts per million. This was done by analyzing
     blank (non-contami%ted) grapes and grapes injected with CN.

     Laboratory Information Bulletin 3352 describes work done by CFSAN on
     the evaluation of the cyantesmo strip for the determination of CN in
     various fruits. The procedure requires 30-40 grams of fruit which are
     placed in a glass jar and mashed. Sulfuric acid is added to acidify the
     sample causing the release of HCN gas if CK is present in the sample. A
     strip of cyantesmo paper is suspended over the sample (not touching)


     Page 32                            GAO/HRD-9@164   FDA’s Actions   on Poisoned   Chilean Fruit
     Appendix V
     F&view of FDA Testing Procedures Used
     to Determine Cyanide in Chilean
     Fruit-Consultants’   Report to GAO




--
     and the lid is immediately placed tightly on the jar. A positive response
     to HCK is indicated by the paper changing to a blue color.

     CFSAN studied a variety of fruits and observed negative results for all
     uncontaminated fruit. Positive results were found with crushed pits of
     nectarines and peaches which are known to contain an organic type of
     CN which can yield HCN upon addition of sulfuric acid. (J. Fleming, con-
     sultant, has evaluated this same procedure for a variety of food com-
     modities and found no false positives. Crushed apple seeds, also known
     to contain an organic type of CN, yielded HCN upon addition of acid and
     gave a positive test with the cyantesmo paper strip). The CFSAN studies
     with sulfite and old cyantesmo paper strips were carried out using
     proper analytical procedures. The results obtained for the sulfite studies
     agree well with similar reports in the literature on the negative effects
     of sulfite on CNdeterminations.

     Laboratory Information Bulletin 3383 describes a rapid sample prepara-
     tion procedure which omits the distillation step of Bulletin 3029
     (method for CNin tea using chloramine-T). It employs centrifugation for
     fruit samples. From the results presented, the centrifugation step is
     more than adequate for CN determination in the fruits studied (CN could
     be detected at levels down to 0.006 parts per million or less). These
     results agree with those obtained by the FDA Philadelphia laboratory and
     the FDA Cincinnati laboratory (Fricke) for grapes, using the same
     method. However, rather than using only 587 nanometers wavelength of
     light, the Philadelphia and Cincinnati laboratories scanned the whole
     visible wavelength range (spectra) to better observe the absorbance
     maximum at 587 nanometers and to observe the shape of the spectra
     which provides additional qualitative information for identification pur-
     poses. This is good analytical chemistry.

     All of the above studies were carried out under the principles of good
     laboratory practice and were appropriate to the work carried out by the
     FDA Philadelphia laboratory on the Chilean grapes. The studies
     described in Bulletins 3352 and 3383 confirm that the work carried out
     by the Philadelphia laboratory was indeed valid.

     D. Substitution of Centrifugation        for Distillation by the FDA in Grape
     Sample Preparation

     As mentioned in section C above, the consultants have no difficulty in
     accepting this substitution. FDA studies with blank (uncontaminated)



     Page 33                            GAO/HRD-W164   FDA’s Actions   on Poisoned   Chilean   Fruit
Appendix V
Review of FDA Testing Procedures Used
to Detennlne Cyanide in Chilean
Frult-Ckmsnltanta’   Report to GAO




grapes and a variety of other fruit (FDA laboratories in Philadelphia, Cin-
cinnati and CFSAN in Washington) all showed that the centrifugation was
adequate. It is faster than the distillation and requires less sample, both
of which were prime requirements during the Chilean grape crisis. In
addition, previous experiments by analysts at the FDA Philadelphia labo-
ratory using spiked yogurt samples showed that the distillation proce-
dure yielded reduced recoveries of CN. This also was a factor in not
using the distillation procedure for the grape samples.

II. Did FDA Properly Conduct the Testing and Correctly Analyze the
Results?

A. Overall, and considering the circumstances, the consultants found the
FDA work to be very thorough and carried out with care. Many suspi-
cious samples were photographed before analysis. Upon finding the CN-
positive grape sample, as indicated by two cyantesmo strip tests and the
chloramine-T test, efforts were made todetermine if it was a false posi-
tive. These included analyzing the SO, pad, stamped ink label, the paper
label and even the photographic film used to photograph the samples.

(1) The FDA -did retain part of the suspect grapes. The consultants were
shown the remainder of the original extract (made basic with sodium
hydroxide) which tested positive twice by the cyantesmo test and posi-
tive by the chloramine-T method. Also FDAhas retained the remaining
half of the third grape (which had a white ring around a small slash or
slice mark) in Cincinnati.

The analyst who did the tests on the three suspect grapes chose two for
analysis and retained the third for use later. Two grapes were chosen in
order to have enough material for the analysis. This also would yield an
average CN value for the two grapes. Considering that only three grapes
were available, the consultants feel that the selection of two grapes for
the test was appropriate. The third grape remained untouched (not
mashed nor acidified) for later analysis. The question of whether only
one grape should have been used for analysis is not important in light of
the results found. It is clear that at least one of the grapes contained
measurable CN.

(2) As described above (sections C and D), the modifications to the chlo-
ramine-T method were done using proper analytical procedures. The
modifications were evaluated using reagent blanks, blank (uncontami-
nated) samples, spiked (injected) samples and several different types of
fruit.


Page 34                           GAO/HRD9@164   FDA’s Actions   on Poisoned   Chilean Fruit
Appendix V
Review of FDA Testing Procedures Used
to Detennlne Cyanide in Chilean
Fruit-Ccmsultants’   Report to GAO




(3) The cyantesmo test involves a selective reaction for CN. The color
change strongly indicates the presence of CN in the samples. The chlora-
mine-T test was performed on a portion of the same extract to confirm
the results obtained by the first test. Because uncontaminated grapes
yield negative CN values for both tests, the only conclusion that can be
drawn is that the positive results are due to contamination (deliberate or
otherwise) with a cN-containing substance. As mentioned in section A,
the two different tests used by FDAare very selective for CN. No other
substances (that do not contain CN) cause false positives in both of these
tests.

(4) The level of CN determined in the positive grapes by the chloramine-
T test was about 8 times higher than the minimum quantity detectable
with the test (assuming the detection limit was 3x the level of the blank
grape). The CRXN studies (FDABulletin 3383) found a minimum detect-
able level of 0.006 parts per million cNin the fruits examined. This detec-
tion limit is about 80 times less than the 0.51 parts per million detected
in the positive grapes by the FDAPhiladelphia Lab. These results indi-
cate that the 0.51 parts per million level determined in the positive
sample was a definite, unambiguous positive result.

(5) The consultants could find no evidence from the calculations and
raw data provided by FDAthat the concentration of CN should have been
0.28 parts per million instead of 0.51 parts per million. The quantitation
was based on a comparison of the results of the test solution (grape
extract) to a standard solution containing a known quantity of CN. The
calculated value was corrected by subtracting the spectrophotometer
reading from a known blank grape sample. The difference is attributed
to “added” CN. Parts per million were calculated by dividing the amount
of CN found by the weight of grapes taken for the analysis. The consul-
tants’ own calculations confirmed that 0.51 parts per million is the cor-
rect result.

(6) Independent studies by the University of California suggest that the
grapes which tested positive for CN must have been accidentally contam-
inated with CN by FDA within 4 hours of analysis. Their conclusion is
based on the appearance of the contaminated grapes, the levels of CN
found and the results of their own time studies on deliberately contami-
nated (injected) grapes.

The consultants questioned FDA personnel in detail on exactly how their
analyses were carried out and how standards and spiked samples were
included in the analytical procedures. They indicated that the analyses


Page 35                           GAO/HRB9@164   FDA’s Actions   on Poieoned Chilean   Fruit
Appendix V
Review of FDA Testing Procedures Used
to Determine Cyanide in Chilean
Fhlt-Consnltants’    Report to GAO




were done “assembly-line” fashion. The positive sample was the only
positive found in a series of samples analyzed at that time. The likeli-
hood of contamination from the atmosphere appears remote since more
than one sample would have been affected. Also, HCN has a very charac-
teristic odor and would have easily been detected in the air if it were
present. The odor of HCN was noticed by four different analysts from the
one positive sample upon acidification, but not with any other of the
approximately 1000 grape samples analyzed during the crisis). Spiked
samples and standards were prepared by a different analyst in a
fumehood in a different location from where the inspection samples
were analyzed. Thus, the likelihood of contamination from inadvertent
sample spiking appears remote. After each individual analysis glass-
ware was thoroughly cleaned, rinsed and dried in an area remote from
the analytical laboratory before reuse. Contamination from this source
also appears remote. The consultants found that good analytical prac-
tice was followed throughout the analyses. The FDA analysts were fully
aware of the potential for accidental contamination and took appro-
priate steps to avoid it.

Studies similar to those carried out by the University of California were
independently performed by CM in Washington and FDA in Cincinnati
(Dr. Fricke). All studies indicated that CNlevels decreased with time
when injected into fruit. However, in the studies by CFSA~and FDA, Cin-
cinnati, CNwas detected in the grapes up to 21 days after injection.
While these studies showed significant variation among individual
injected grapes, it appears that there is an initial rapid decrease in CNby
the end of the first day followed by a much lower rate of decomposition
or even a levelling off up to 21 days (similar results were observed for
CN-treated apples and plums, by J. Lawrence consultant). Also, studies
by the University of California have shown that CNapparently can
migrate (presumably as HCN, which is volatile) to other grapes and be
detected for up to 21 days, The CNon these grapes apparently does not
affect their appearance after that length of time.

Fruit, such as grapes, injected with CN,showed within a certain period
of time, visible signs of deterioration of quality (dehydration, browning
near injection point). However, the rate of visual degradation in quality
of the grape s was not uniform in the studies. The CFSANstudies were
carried out by injecting very large quantities of CNinto grapes (up to 18
milligrams per grape). Their results indicated that some injected grapes
showed no change in appearance after 2 days of storage at room temper-
ature and up to 6 days when refrigerated. The studies by Dr. Fricke
(where lower amounts of CNwere injected) also showed that some


Page 36                           GAO/HRD-W-164   FDA’s Actions   on Poisoned Chilean   Fruit
Appendix V
Review of FDA Testing Procedurea Used
to Determine Cyanide in Chilean
Frnlt-Consnltanta’   Report to GAO




grapes injected with CN (160-1000 micrograms) lasted up to 16 days
without significant degradation.

All of these studies show that some injected grapes can retain their orig-
inal appearance for a much longer period of time than others. It is some-
what difficult to relate these studies to the results found by the
Philadelphia lab with the positive grapes during the crisis for several
reasons. First, the grapes analyzed during the crisis were “young”
grapes sampled immediately upon arrival in the U.S. The studies by FDA
and University of California may have been done using grapes that were
picked at a later date or stored for longer periods and thus may have
been “riper” than the samples analyzed in the crisis. Secondly, the vari-
ability in results is an indication that all grapes do not necessarily react
in the same way to CN injection. Thirdly, the variability in how the sam-
ples were injected (depth and volume of injection, exactly where in the
grape the injection was made, size of needle used, type of solution
injected: eg. acidic, basic, containing other substances in addition to CN)
could affect the results. (It is even conceivable that juice may have been
withdrawn from the CN positive grapes before injections with CN to mini-
mize the leakage from the fruit.) Fourthly, the crisis samples were
stored in the presence of sulfite pads, the purpose of which was to pre-
vent degradation and likely browning of the grapes. (Sulfite is a known
inhibitor of browning of fruits and vegetables.) These conditions would
likely minimize the visual changes that might have been induced by CN
injection.

In summary, the studies carried out by FDA and the University of Cali-
fornia showed that some grapes can be visually changed in a short time
by CN injection while others are much more resistant, retaining a good
appearance for up to 16 days depending upon levels of CN injected,
freshness of the grapes and storage conditions. Also, CNhas been shown
to remain in injected grapes for up to 21 days. The grapes analyzed in
Philadelphia during the crisis were very fresh, stored under mainly
refrigerated conditions prior to analyses and were in the presence of sul-
fite pads. Under these conditions it is possible that the grapes could
have been injected with CN 2-3 weeks before analysis by FDA.

Based on all the evidence examined, the consultants disagree with the
University of California conclusions that the grapes must have been
contaminated with CN within 4 hours prior to analysis,

B. After an examination of all documents made available to the consul-
tants, and interviews with personnel directly involved in the discovery


Page 37                           GAO/HI?.DW164   FDA’s A&OM   on Poisoned Chilean   Fruit
                         Appendix V
                         Review of FDA Testing Procedures Used
                         to Determine Cyanide in Chilean
                         Fruit--Consultants’  Report to GAO




                         of CN in the two suspect grapes, the consultants believe that there were
                         no deficiencies in the testing that could have materially affected the out-
                         come (see details presented in other sections of this report).

                         III. Was FDA'S Research on Contamination of Fruit with Cyanide Con-
                         ducted in Accordance with Appropriate Scientific Principles?

                         (1) The consultants found no significant deficiencies in the chemical
                         methods used by FDA (CFSANand the Cincinnati Lab) to study the effects
                         of CN on grapes and other fruit. The results indicated that CN can have
                         an effect on the appearance of fruit which is dependent on time, temper-
                         ature, quantity of CN injected and ripeness of the fruit. (See detailed
                         comments in Part A section II A of this report.)

                         (2) The studies by FDA and other research groups (University of Cali-
                         fornia, and others sponsored by the Chilean interests) have addressed a
                         number of issues concerning different aspects of CNcontamination. All
                         of the studies used either potassium or sodium cyanide to idect into the
                         grapes. However, there are other cyanide containing substances that
                         could have been injected (e.g. amygdalin or other cyanogenic glyco-
                         sides). It may be useful to carry out injection studies with these types of
                         compounds to observe degradation of CN and the visual quality of the
                         grapes with time. Also, a detailed study on the storage of grapes in the
                         presence of SO, pads may contribute information relating to the effect of
                         SO, on the stability of CN in the grapes and to the change in visual
                         appearance with time.


Part B. Additional       The consultants questioned in some depth the FDA analysts who tested
                         the CNpositive grapes. The analysts explained that they had extensive
Consultants’ Comment23   experience with the cyantesmo test and the chloramine-T test and, in
Interviews With FDA      fact, performed about 1000 tests on yogurt samples immediately before
Analysts                 the Chilean grape crisis. All analysts knew and understood the basic
                         principles involved in the analyses and carried out the necessary analyt-
                         ical tests to ensure that any modifications to existing procedures were
                         valid. The consultants were impressed with their competence.

                         The consultants questioned the analysts on the discrepancy between
                         results of the Philadelphia lab and the later test carried out by Dr.
                         Fricke of the Cincinnati lab several hours later on the same sample. It
                         was learned that upon addition of sodium hydroxide to the grape sample
                         (to prevent loss of HCN), the color of the liquid changed from purplish



                         Page 38                           GAO/HRBSO-lf34   FDA’s Actions   on Poisoned Chilean   Fruit
RevkwofF’MTest&ProcedureaUsed
to Determine Cyanide ln Chll-
Frd-nsnlmts           Report to   GAO




(acidic or neutral) to pale green. The pale green mixture was trans-
ported to Cincinnati by H. Miller. However, upon arrival, Mr. Miller
remarked that the color of the sample was again purplish, possibly indi-
cating a return to acidic (or neutral) conditions. Under these circum-
stances, any remaining CN may have been lost as HCN during transit or
possibly have reacted further with sample constituents reducing the
amount remaining for analysis by the Cincinnati lab to below their
detection limit. The consultants have no difficulty in accepting this pos-
sibility. Basic pH was used to prevent volatile HCN formation by con-
verting it to water soluble, non-volatile CN ion. This is normal procedure
to prevent the loss of volatile acidic substances. However, studies car-
ried out since the grape crisis have shown that even in basic solution CN
may decompose significantly in a few hours (University of California
study and experience of J.F. Lawrence, consultant).

Sampling and Documentation Procedures

The consultants briefly discussed the sampling procedure used by FDA to
obtain samples of grapes from the suspect shipment. The sampling
approach was considered appropriate for the detection of deliberate CN
contamination in the fruit. However, the consultants did not study the
background statistical criteria used by FDAto select the sampling
procedure.

The consultants found no significant flaws in the chain of custody docu-
mentation or procedures used by the FDA.Some of the documentation
and lab reports were not clearly presented but all essential information
concerning sample labelling, transport from one person to the next, lab
testing and results of tests were documented. The consultants found no
errors or omissions that would have had an impact on the results
obtained by the FI~APhiladelphia laboratory.

Conference Call With Rerxesentatives of the GAO and Chilean Interests

The consultants participated in a conference call on 16 March 1990 to
discuss, in particular, recent findings by the University of California
related to CN in grapes. These included migration of CN and the efficacy
of cyantesmo testing. Some discussion also centered on the effect of sul-
fite on the analyses and differences between distillation and centrifuga-
tion in the chloramine-T test. The following are some comments.




Page 39                                 GAO/IIRD9O-164FM'sActioneon PoisonedChikanFruit
                Appendix V
                Review of FIbA Testing Pmcedurea Used
                to Determine Cyanide in Chilean
                kuit-&MdtantS’        Report to GAO




                a) Migration of Cyanide

                It appears that CN may migrate from injected berries to nearby fruit.
                The migration seems to involve conversion of CNto volatile HCN which
                escapes and may adsorb onto the surfaces of other grapes. Direct con-
                tamination of neighbouring berries by contact with liquid from the
                injected berries is also possible. The degree of contamination via migra-
                tion would likely depend upon the quantity of CNinjected into the grapes
                and the storage conditions. If only small quantities were initially
                injected, the amount of CN migrating might not be detectable by the
                cyantesmo or chloramine-T tests.

                b) Efficacy of Cyantesmo Testing

                The studies by the University of California showed that results by the
                cyantesmo test are affected by the quantity of CN injected into the
                grapes and the length of time the grapes are stored. This does not
                appear unusual and would be expected knowing the behavior of CN in
                injected fruit. In some cases, the second cyantesmo tests were more posi-
                tive than the first ones. It is not known why this occurs.

                c) Comparison of Centrifugation         and Distillation

                No research has been done on a direct comparison of the centrifugation
                method with distillation for injected grapes. It is possible that recoveries
                and detection limits of CN could be different depending upon how CN is
                held in the samples. Sulfite can cause CN losses in the distillation proce-
                dure (C.H.P. van Eeden and A.W.J. de Jong, Z. Lebensm. Unters. Forsch.
                181,412 (1985)). However, overheating (charring) during distillation
                might lead to CN formation from natural constituents (I. Thompson and
                R.A. Anderson, J. Chromatogr. 188,357 (1980)), thus yielding false posi-
                tives. On the other hand, heating of CN in a food matrix could cause a
                loss of CN by its accelerated reaction with food components. The likeli-
                hood of these occurring can only be determined by analyzing reagent
                blanks, sample blanks and spiked sample blanks.


                The consultants are of the opinion that the FDA did find CN in the two
4. Conclusion   grapes during the grape crisis. After interviewing FDApersonnel and
                reviewing all available information from the crisis and the results of
                many studies carried out after the incident, the consultants believe that
                a false positive reading is extremely unlikely. The overall conclusion on
                the injection studies is that CN can persist in grapes for at least three


                Page 40                           GAO/HED90164    FDA’s AC~~OM on Poisoned Chilean   Fruit
Appemdix V
Review of FDA Testing Procedures Used
to Determine Cyanide in Chilean
Fmit-Cmsnltanta’     Report to GAO




weeks, depending upon quantities injected, condition of the grapes and
storage conditions. The visual appearance of some fruit may only be
minimally affected by CNinjection (again depending upon quantity
injected) while that of others may be more affected. The analytical
methods used by the FDAwere scientifically sound. Their analytical pro-
cedures were carried out under good laboratory practice and their staff
were fully familiar with CN testing. Overall, the consultants could find
no significant error or omission in the FDAwork that would have had an
impact on their findings.

Signatures of Consultants:




 Page 41                           GAO/ERLMJS164   FM’s   Actions   on Poisoned   Chilean   Rnit
Major Contributors to This Report


                        Janet L. Shikles, Director, Health Financing and Policy Issues
Human Resources         Albert Jojokian, Assistant Director
Division,               Rodney Ragan, Assignment Manager
Washington, D.C.

                        Sara Herlihy, Investigator
Office of Special
Investigations

                        Thomas P. Hubbs, Evaluator-in-Charge
Philadelphia Regional   Margaret A. Klucsarits, Evaluator
Office




(108737)                Page 42                      GAO/HRLMO-164   FDA’s Actions   on Poisoned   Chilean Fruit
‘.




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