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The Availability of HPV Chemical Data

In early October 1998, the Environmental Protection Agency (EPA) announced the High Production Volume (HPV) Chemical Challenge program, calling for toxicity testing on 2,800 chemicals imported or manufactured in amounts over one million pounds per year. This program was apparently devised in closed-door meetings between the EPA, the Chemical Manufacturers Association (CMA), and a single interest group, the Environmental Defense Fund (EDF). The program will cost the EPA an estimated $11 million to administer, industry will spend up to $700 million on testing, and millions of animals will be used and killed in the crude tests that are required.

Cause for Concern

As an organization working to protect public health and encourage alternatives to animal testing, the Physicians Committee for Responsible Medicine (PCRM) was immediately concerned about the HPV program when we were made aware of it in November 1998. We were particularly concerned that the program calls for testing compounds whose toxicity is already known, such as cyclonite (rat poison), tetraethyl lead, and carbon tetrachloride, and other substances that are clearly not hazards, such as caffeine, citric acid, and lactic acid. We found that the data availability study upon which the program is based is seriously flawed. Upon further investigation, it became clear that the HPV program will not protect public health, will not result in regulatory controls on hazardous substances, and is not sound policy.

As detailed in this report, PCRM researchers found that EPA’s review contains numerous major errors. Indeed, sufficient data are indeed available to perform a basic hazard assessment for a majority of the substances. As the HPV program is predicated upon the assumption that sufficient data do not exist to make a basic hazard assessment, our findings call into question the very basis of this massive program. The report highlights the need to defer implementation of the HPV Challenge program until the EPA performs a sufficient review of extant data and determines what, if any, testing is actually required.

Methods

We selected 35 chemicals from those listed in the EDF’s Toxic Ignorance report, cross-referenced with the EPA’s HPV Challenge Program Chemical List. These 35 represent half of the 71 chemicals the EDF identified in its report as lacking preliminary human health tests. To assess the availability of previous test data, we utilized only publicly available databases in conducting our search. These included the Hazardous Substances Data Bank maintained by the National Library of Medicine, the Integrated Risk Management System maintained by the EPA, and toxicological profiles issued by the U.S. Department of Health and Human Services’ Public Health Services Agency for Toxic Substances and Disease Registry. Other publicly available databases hold additional information on HPV chemicals. For example, MEDLINE and TOXNET are both maintained by the National Library of Medicine. These latter sources were not considered in this review.

Findings

Of the 35 chemicals initially selected from the EDF report, only 22 remain relevant to the HPV program. Two1 were removed from the EPA’s HPV list during the initial “scrubbing” when it was determined testing, “would not further our understanding of the chemical’s properties.” Four2 were removed from the list because they are currently being tested by the Organization for Economic Cooperation and Development (OECD). Three chemicals3 do not appear on the current EPA HPV list because they are either inorganic or are no longer produced in high volume. Additionally, 24 of the 35 clearly do not need additional testing because they only lack neurotoxicity data, an endpoint not covered in the HPV program. Similarly, two5 additional chemicals lack only preliminary carcinogenicity screening, another endpoint not addressed in the HPV program. Of the 35 chemicals in this subset, therefore, 13 have since been exempted by the EPA from HPV program.

For 13 of the remaining 22 chemicals (60%) in our sample, our researchers easily located publicly available documentation of previously conducted animal experiments and known human health effects, using only three public sources to locate this information. The chemical industry has at its disposal far more information. Thus, our review in fact greatly understates the available toxicity data for these chemicals. Clearly, much of the HPV program will consist of duplicative and wasteful animal experiments.

Shared Concerns

Similar concerns were noted by The Dow Chemical Company in its initial response to the EDF. Dow’s stated position highlights the problems that arise when relevant data is ignored because it may not fall within the unnecessarily narrow confines of the OECD’s Screening Information Data Set (SIDS) that forms the basis of the HPV Program. As Toxic Ignorance reports, “Dow noted that tests outside the categories established in the OECD screening process should in some cases be considered superior to the OECD-required tests, and thus that a chemical could in fact have been adequately tested for screening purposes notwithstanding a negative score based on the lack of an OECD-required test.”

Other relevant concerns were raised by the National Research Council, in its 1984 report, Toxicity Testing: Strategies to Determine Needs and Priorities. This study examined not just data availability, but also addressed the question of how to best fill any data gaps that may exist. The results of the NRC study stand in sharp contrast to methodology of the HPV program. The NRC concluded that prioritization of chemicals must occur so those chemicals which actually pose the most danger are tested first. The report states, “Long lists of candidate chemicals need to be reduced to short lists through screening, which yields increasing amounts of information on decreasing numbers of chemicals and possible tests. The two key elements for screening are estimated human exposure and suspicion of toxic activity.” (emphasis added). Both of these elements have been completely excluded from the HPV program. Ironically, proponents of the HPV program continue to incorrectly cite the NRC report in an attempt to support testing that is devoid of the Council’s recommendations– prioritization based on exposure assessments and known toxicology data.

Relevant Data Abound

In this report we cite numerous examples of chemicals that clearly have sufficient data for hazard assessment.

  • The EDF and EPA conclude that cyclonite does not have available chronic toxicity data. PCRM easily located seven published chronic toxicity experiments conducted on cyclonite within the past 15 years.
  • 1,4-dioxane, another chemical that is purportedly devoid of chronic toxicity data, has six separate chronic toxicity tests detailed herein.
  • Carbofuran, another chemical similarly listed, has had eight different chronic toxicity assays conducted on it in the last ten years.

Similarly, many chemicals are listed as missing basic information about chronic health effects despite the fact that claims about their negative health effects abound on the EDF’s own chemical Scorecard Web site.

  • Cyclohexanol is said to be missing chronic toxicity data, yet the EDF acknowledges it is suspected of acting as a cardiovascular toxicant, liver toxicant, kidney toxicant, neurotoxicant, reproductive toxicant, respiratory toxicant, and skin toxicant.

Additionally, where relevant, PCRM’s report includes information about chemicals already subject to federal regulations. For some substances, the Occupational Safety and Health Administration (OSHA) and other agencies have limited acceptable exposure levels, issued special handling instructions based on chronic health concerns, or taken other regulatory actions. Further testing is unnecessary for chemicals that are clear-cut toxins and are already subject to regulatory controls.

  • Carbon tetrachloride is slated for chronic toxicity testing, yet the state of California and the EDF recognize it as a carcinogen. The National Institute for Occupational Safety and Health already recommends that, “exposure be limited to the lowest feasible concentration.” Many companies began to remove carbon tetrachloride from their workplaces as early as 1980, due to its known chronic health risks, and it has been banned from use in products intended for the home.

Human Data Most Predictive

The EPA ignores both incidental human exposures and even well-conducted human clinical trials.

  • 2, 4-Dinotrophenol was prescribed as a diet pill until it became clear that a disproportional number of those taking it developed cataracts. Its use as a diet aid was subsequently discontinued, in the meantime extensive studies were conducted related to the interaction of the chemical in humans. Its chonic human toxicity is well documented, yet the HPV Challenge calls for a battery of animal tests.
  • Similarly, in 1978 NIOSH recommended that trimellitic anhydride “be handled as an extremely toxic agent in the workplace. Exposure to this compound may result in noncardiac pulmonary edema (apparently without benefit of a pulmonary irritation warning), immunological sensitization, and irritation of the pulmonary tract, eyes, nose, and skin…the exposure standard suggested was 0.05 mg/m3 or less for susceptible individuals.” This Intelligence Bulletin was issued based on five epidemiological studies involving workplace exposures to trimellitic anhydride. Despite this existing knowledge, the EPA wants to require chronic toxicity tests on animals with trimellitic anhydride.

Volume Does Not Equal Risk

The HPV program is based on the premise that, because chemicals are produced in large quantity, exposure risk for them must also be high. This assumption is simply conjecture, and is poorly supported.

The EDF claims in Toxic Ignorance that, “in the absence of solid information to the contrary, use in such volume [>1,000,000 lb./y] is presumably likely to be leading to significant exposures and releases to the environment.” The EDF does not, however, provide any cogent argument as to why this assumption is to be accepted. The EPA has in fact stated separately that, “Production data generally should be combined with other data in an effort to minimize some of the inherent weaknesses of using production data as a surrogate for exposure.”1

For many chemicals, toxicity is already sufficiently clear that containment, not further testing, is required for protection of the environment and public health.

Flawed Approach

The EDF maintains in Toxic Ignorance that, “Step one towards a solution lies in simple screening tests, which manufacturers of chemicals can easily do.” This is not, however, what the OECD considers as the first step to address potential hazards. The OECD SIDS program, upon which the EPA claims the HPV challenge is based, contains fundamental steps that have been omitted from this initiative. The OECD guidelines call for an initial phase in which data are gathered, compiled in the form of a SIDS Dossier and SIDS Testing Plan, and then reviewed by experts who decide what additional testing, if any, is warranted. In what can only be considered the height of irresponsibility, the EPA has stated it will not even review test plans, let alone provide a full assessment of extant data to ensure wasteful and duplicative testing is prevented.

Assessing the Real Risks

According to the EPA’s own data adequacy study, there are 91 HPV chemicals that are included on the Toxics Release Inventory and which are released into the environment in excess of 1 million pounds per year. These are the chemicals that pose a risk to humans and the environment. For good reason, these are also the chemicals for which the most screening tests have been conducted. The EPA’s own numbers on these 91 chemicals show that 74% of them have the full battery of SIDS tests completed and all of them have either three or four of the specific SIDS endpoints filled. Clearly, for chemicals where there is potential risk, action has been taken to determine the relative degree of this risk.

Conclusion

It is clear that the EPA review of HPV chemical data was extremely limited and severely flawed, and is insufficient to justify a program such as the HPV Chemical Challenge.

The HPV testing program should be delayed to incorporate adequate data collection and review and to ensure a mechanism is in place to complete this review prior to any new testing. A delay is also necessary to allow non-animal test methods to be validated and used in this program. Rushing forward into a massive battery of costly, unnecessary, and cruel animal tests will not protect the environment or safeguard the public from hazardous chemicals.

References
1. Sorbitol (50-70-4); Glycerol (56-81-5)
2. 4,7-Methano-1H-indene, 3a,4,7,7a-tetrahydro (77-73-6); 1-Butanol (71-36-3); Silane, dichlorodimethyl (75-78-5); Sulfuric acid monododecylester (151-21-3)
3. Aluminum (7429-90-5); Carbon Black (1333-86-4); Cellulose (9004-34-6)
4. 1,3-Benzenediamine-ar-methyl (25376-45-8); Urea, N-(4-chlorophenyl)-N-(3-4-dichlorophenyl) (101-20-2)
5. Phosphoric acid, triethyl ester (78-40-0); Benzene, 1-chloro-2-methyl (95-49-8)

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