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Pesticide Safety Fraud

Fraudulent safety tests carried out overseas mean that New Zealanders should be more cautious about the pesticides they are using.

By Tim Frederikson

A recent court case in the United States [see accompanying article, Anatomy of Deception] has highlighted concerns that many of the pesticides in common use in New Zealand have inadequate or downright fraudulent safety data.

It is becoming apparent that this is not an isolated case. A number of testing facilities contracted to test pesticides and other substances for chemical companies have been found to be using questionable practices with regard to their testing methods. The commercial sensitivity and legal ramifications of such fraud has meant that much of this information is only now coming to light, often years after occurring.

In one case, that of Craven Laboratories Inc, some 48 pesticides were found by the US Environmental Protection Agency to have safety data that was fraudulently documented. Of these, 28 are currently registered for use in this country.

To date, not a single pesticide involved in this case and registered in New Zealand has been subjected to suspension here. The reaction in Europe to the revelations in the United States has been stronger. There, those companies whose products have been affected by testing fraud have been asked to validate the safety data of the products under question. In the United States, chemical companies have been asked to submit replacement tests to ensure that required safety data is available and accurate.

Currently there are approximately 290 registered pesticides in New Zealand. Of these, 117 are the subjects of falsified or otherwise defective toxicological studies performed by Industrial Biotest -- a company originally indicted ten years ago.

Over the past decade there have been several attempts to draw attention to the defects in our registration, validation and auditing procedures for compounds introduced into New Zealand.

Safety Data Desired

In the early 1980s, the Friends of the Earth tackled the New Zealand Agricultural Chemicals Board for safety, toxicological and environmental data submitted by registrants for certain pesticides used in New Zealand. The board refused to release safety data -- other than generalised label claims -- to users of these pesticides, citing commercial sensitivity as one reason.

However, the release of information required by users and handlers would not necessarily have endangered profitability, as sensitive technical information was not needed. Rather, it was aimed at gaining basic information to develop appropriate safety training and disposal techniques. The lack of such information hindered the development of training and disposal strategies.

By way of illustration, it has been known since 1947 that if a user is exposed to organophosphate compounds, the effects can be combatted by the administration of atropine sulphate. However, in the case of exposure through an accident involving injury and pain, an injection of a morphine-based painkiller could kill the victim within two minutes if atropine sulphate had also been administered. As late as 1982, this fact was still unavailable to the New Zealand pesticide user, and today does not appear on containers of organophosphate compounds.

In May 1989, an independent report commissioned by the Ministry for the Environment noted that our pesticide toxicological data was, in effect, a rubber-stamping exercise of the data supplied by companies wishing to gain pesticide registration in New Zealand. It made no mention of the IBT scandal which affected almost half of the pesticides registered at that time in this country.

The 117 compounds in New Zealand affected by IBT falsifications and the 28 arising out of the Craven investigations comprise many of our most popular and widespread pesticides. Many have been here for such a length of time as to be regarded as "traditional" compounds.

Consequently users, handlers and producers have been subjected to significantly increased levels of exposure than the original toxicological and environmental studies led us to believe was appropriate. It was no accident that the fraudulent testing regimes led companies to believe their products safer than they actually were...

In spite of the publicity surrounding cases like IBT and Craven, New Zealand still does not require manufacturers to provide accurate test data. We still accept US data knowing that it has often been falsified, we do not devote the resources to enable our experts to check the veracity of submitted data, and we still fail to suspend, revoke or cancel registrations of substances which have been proven elsewhere to have harmful effects.

The list of substances is extensive -- most home gardeners and market gardens would use more than one of the substances shown now to have previously unreported effects such as nervous system effects and greater soil persistence. It is interesting to note also that, while a total ban has been placed on organochlorine pesticides in New Zealand, no action has been taken on Glyphosate, 2,4-D or Sencor when the evidence in the United States is overwhelmingly in favour of severe restrictions being imposed on their use.

Pesticides are not the only compounds of concern -- it is known that questionable safety data has also been used to support the registration of medicines. Last February, reports from the Audit Office raised alarms concerning the safety and effectiveness of medicines imported, manufactured and used in New Zealand.

Perhaps the time has come for New Zealand to demand accountability from manufacturers by introducing compulsory testing in approved facilities in this country. While it may cost millions to undertake full-scale studies, there is room for confirmatory, independent testing that would make the New Zealand user less vulnerable to dubious overseas work. Some industry observers have suggested that New Zealand could market such services competitively.

Certainly, there is justification for reviewing the status of the 145 compounds currently registered here under old toxicological data.

It cannot be said that we lack the facilities and professional abilities to conduct such a review, as the former DSIR and its offspring, AgResearch, has maintained very high standards of work in substance data preparation and verification.

Reliance on the voluntary updating of product toxicological data has produced barely a ripple in the records of our regulatory authorities, and the indications are that such updating is vitally needed.

Tim Frederikson is an industrial safety consultant.

Anatomy of Deception

On Tuesday 22 September, 1992, Craven Laboratories Inc, its president and three employees were imprisoned on 20 counts in connection with conspiring to and carrying out falsification of pesticide test results. Eleven other employees pleaded guilty to charges of making false statements and conspiracy.

Craven Laboratories had contracts with a number of pesticide manufacturers to conduct 48 pesticide residue tests for submission by their clients to the Environmental Protection Agency. Eleven multi-national pesticide producers are instituting proceedings to recover the millions of dollars paid to Craven Laboratories over many years.

The company came to the attention of EPA investigators early in March 1991, when the agency received information that the lab had "manipulated" studies and results for 16 pesticides -- Maneb, Polyram, Blazer, Poast, Ethyl Parathion, Diquat, Lontrel, Tordon, Linuron, Mancozeb, Whip, Roundup, MCPB, Goal, Rally and Terrachlor.

The EPA launched an immediate investigation which resulted in the confirmation of the "manipulation" allegation and the uncovering of similar data inconsistencies for a further 34 materials. Despite this, nobody appears to be suspending or revoking the registrations of the pesticides identified as being subjected to false testing.

Not An Isolated Case

Information is continuing to emerge concerning the fraudulent activities of other companies involved in testing pesticides, fungicides, herbicides and other material.

The procedural shortcomings and fraudulent data of Affiliated Medical Research Laboratories Inc. saw the EPA treat its data results very cautiously. Despite this, more than 15 pesticides subsequently received EPA registration based solely upon this company's submissions. Although the lab has ceased operations, those 15 pesticides remain registered and the manufacturers have not been required to submit amended or new data in support of their toxicological claims.

Bio Safety Research Laboratory Inc had studies continually rejected by EPA toxicologists on the basis of unclear dose determinations and the lack of animal examinations. Inquiries revealed that the lab conducted experiments on 8% of the total number of animals they claimed to have available for test/control groups. Registration of pesticides under their contracts was granted with nothing more than a few words of warning to the company's executive director.

Biospherics Inc operated for several years following the EPA's admonition that "your method of evaluation is not adequate for regulatory purposes". The company's file was tagged by the agency to ensure that its results would not be used as the sole data for registration claims, but some 11 pesticides tested solely by Biospherics still managed to enter the market.

Gulf South Research Institute was investigated, charged and convicted of offences involving the falsification of test data, concealment, obstruction, making false statements and breaches of the Federal Insecticide, Fungicide and Rodenticide Act. Their test data has never been reviewed.

Bribery and Fraud

In 1977, the EPA, Food and Drug Agency and the National Cancer Institute received an allegation from a generic drugs manufacturer that an FDA official had requested a bribe to "fast-track" a drug for approval. Inquiries revealed that the allegation had foundation.

The investigation centered upon recently issued approvals, and one company's name -- Industrial Biotest Laboratory Inc (IBT) -- appeared time and time again, linked to falsified data submitted to the EPA, FDA and NCI.

Industrial Biotest was not a small, unknown testing agency -- its results have been accepted for more than 2,000 registrations. In June 1977, a moratorium was placed on registration actions involving data from IBT, and certain registrants were advised that their raw data needed to be audited for their registrations to retain validity.

One example of IBT's "testing" activities concerns the registration of Harvade, a herbicide manufactured by Uniroyal. The investigation found that the five test results submitted by IBT to the company were identical in all respects to results provided for three other pesticides.

While some laboratory animals had been subjected to testing, IBT's claims that rats were used were found to be false -- the tests had been performed on dogs. Investigators found that the initial rat population had died through causes other than exposure to the pesticide. Examples were given of technicians failing to feed and water the rats over long weekends and holidays, of rats dying through diseases due to unhygenic facilities, of rats being fed rat poison by mistake, of rats escaping, of rats being shifted between cages, and the accidental substitution of control group animals by those of the test group.

Finally, when it became clear to IBT that the tests had been totally compromised, the company director ordered the substitution of rats by dogs, and manipulated the doses to the new test animals to give "at least some sort of results".

When these dogs were sectioned, it was found that few exhibited any similarities to the few remaining test rats, and all references to dogs being tested were deleted from the records. This still was not sufficient to hide the disaster, and the company then used results from other pesticides of similar chemical construction, and provided these results to Uniroyal for their registration application.

In 1969, Syntex Corporation contracted IBT to test a new anti-arthritis drug called Naprosyn, a drug still on the market. Syntex was enthusiastic about the drug because their own preliminary tests indicated that it did not have the same side-effects as similar drugs. To validate their data they needed a long-term rodent study, and IBT won the tender.

The tests proceeded in an apparently orderly fashion until October 1970. At that time, lab technician Phillip Smith was assigned to write the study report, but when he tried to find the blood and urine data, he discovered the test rats had been sectioned before any such data had been obtained. Leaving that part of the report blank, Smith passed the documents to the head of Rat Toxicology, Paul Wright, and advised him of the "difficulty".

Instead of advising Syntex of the mix-up, Wright and James Plank (Group Leader, Rats) filled the blank spaces with false data. They even filled in the signature boxes on all 30 pages with a rough approximation of Smith's signature and mailed the documentation to Syntex.

Within two weeks Syntex responded, but not favourably. They stated that they were "convinced that the report would be rejected by regulatory agencies in the United States, United Kingdom, Canada and Germany. Would you please see the report is corrected and returned at the earliest?"

Two technicians vainly searched for the missing blood and urine data. Reporting to IBT's Manager of Toxicology, Moreno Keplinger, the two were told "I'll take care of it", and a revised report was sent to Syntex. Syntex then applied to the FDA for the registration of Naprosyn and it was granted.

In 1975, Naprosyn came to the attention of the FDA due to the number of tumours being reported by doctors who prescribed the drug to their patients. A leading US pathologist, Dr Adrian Gross, reviewed the data held by the FDA and found numerous discrepancies and deficiencies in IBT's methodology and data.

Gross was so alarmed that he continued his search on more than 2,000 IBT studies and what he found convinced him that the facility was "mentally manufacturing" at least 65% of its test data.

In a now infamous incident, IBT re-equipped the facility with paper shredders and proceeded to "strip file" huge volumes of raw data, studies and client lists. By June 1977, hundreds of studies covering the carcinogenic effects of cyclamates, artificial sweeteners, herbicides and substances used in the manufacture of plastics went through these overworked machines.

However, all IBT studies submitted by manufacturers to regulatory authorities were held by those agencies. On 22 March 1978, the EPA requested all pesticides registrants who had used IBT's data to provide their raw data so that registration applications could be audited and validated.

This uncovered additional shortcomings -- data had been shredded, lost or had the data authentication removed. IBT personnel held questionable qualifications, were severely overworked and were poorly supervised. Undocumented protocols were used, documented ones were changed, and several were interchanged with other programmes. Few records were kept concerning feeding programmes, dose rates, timing of feeds and which animal was fed what chemical. Animals were poorly identified, they were often gang-caged, and in many instances were recorded as having died more than once. Several hundred animals were recorded as having developed lesions and, after dying and being sectioned, to have had no lesions and dying again through "natural causes".

The huge investigation saw the EPA and Canadian authorities agree to share the review of all IBT studies. However, the exercise was overwhelming and, in July 1980, they agreed not to pursue the validation of registration data if "...the registrant had submitted, submits or agreed to submit a suitable replacement study; and agreed to having the IBT study declared invalid for the purpose of future registration actions."

IBT's world fell apart. The company, its staff and the FDA "fast-track specialist" were indicted on counts of corruption, bribery, falsification and concealment. In October 1983, IBT founder Joe Calandra, Wright, Keplinger and the FDA official were sent to prison.

One telling incident involved company lawyer, Merrill Thompson, who told the jury that after working with IBT for almost a year, he refused to defend the company in an FDA investigation.

"As I got into it and worked on these things more and more, and worked with the IBT people, and looked at the evidence of other practices within the industry, I decided I couldn't defend IBT's practices," he said.

Tim Frederikson is a chemical safety consultant.