The Availability of HPV Chemical Data
Background
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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