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Background
An audit of the
Hercules 009 Landfill Superfund Site conducted by the EPA Inspector General
(IG) found the toxaphene analytical method used by EPA Region 4 did not
report all of the toxaphene present in samples. The IG made specific
recommendations to correct the problem, and EPA Region 4 responded to the IG
on June 20, 2006. However, instead of implementing the IGs' recommendations,
Region 4 proposed a new method of toxaphene analysis and risk assessment.
The new method proposed by EPA Region 4 and the Georgia Environmental
Protection Division for measuring toxaphene referenced only a single
published paper.
This
Technical Assistance Report excerpted from:
Review and Comments on the paper
“Development of a Reference Dose for the Persistent Congeners of Weathered
Toxaphene based on
In
Vivo and
In
Vitro Effects
Related to Tumor Promotion”
by Simon and Manning, 2006 published in the Journals of Regulatory
Toxicology and Pharmacology.
Overview
This article seeks
to redefine environmental toxaphene monitoring using tumor promotion as the
only result of exposure. However, rather than offer concrete scientific
modeling for a tumor promotion effect of the chemical, the authors seek to
minimize established use of toxaphene genetic mutation data, while at the
same time ignoring compelling data showing toxaphene can, and does, cause
cancer. Further, the authors propose an analysis using only three of the
several hundred compounds that make up toxaphene. The paper provides no new
experimental observations, no new survey data, and no new calculation
algorithms. Instead, the authors use a subset of toxaphene publications to
support their views.
Toxaphene Definition
The Simon and
Manning paper defines toxaphene as all of 800 different chemicals possible
for the chlorination of camphene. In the third paragraph, the authors offer
definitions for technical toxaphene (TT), and weathered toxaphene (WT), with
weathered defined as degraded technical toxaphene.
“Degraded” though,
just means changes in congener (the individual chemicals in toxaphene)
occurrence. Toxaphene manufacturing wastes dumped in streams and borrow-pits
in Brunswick, Georgia, would be considered technical toxaphene with Simon
and Manning's definition. Further, the “toxaphene-like” compounds found on
elementary schoolyards and in neighborhoods throughout Glynn County,
Georgia, are also technical toxaphene, as defined by Simon and Manning.
Essentially, with
this definition, there is no need for any definition other than “TT” for
toxaphene found anywhere on earth; and we concur with the authors’
definition.
Model based on Tumor Promotion
Simon and Manning
argue that environmental toxaphene monitoring should be based on tumor
promotion. The authors provided three arguments in support of their logic:
lack of human mutagenicity; lack of significant developmental defects; and,
carcinogenicity.
Mutagenicity of Toxaphene
The authors’
statement regarding toxaphene genotoxicity - the ability to cause genetic
damage - in humans is confused and lacking in logic. Carcinogenicity, the
formation of tumors, is a complex subject. Typically, the process requires
damage to cellular DNA - but not always. Some chemicals that participate in
the cancer process are promoters, not initiators, in the sequence of tumor
formation. Since science cannot always predict a chemicals’ carcinogenicity,
best practices require that, if any type of study points to potential
genotoxicity, then the material is presumed genotoxic until proven
otherwise.
The science proving that toxaphene is genotoxic in bacterial systems is
compelling. TT is mutagenic in the Ames test, a widely-accepted bacterial
test for quantifying DNA damage. Simon and Manning correctly note in their
article that toxaphene induces Sister Chromatid Exchange (SCE) in higher
cells under laboratory conditions. Visual microscopic damage to chromosomes,
the organized complex of DNA and proteins within higher cells that is
visible during cellular division, is a good indicator of genotoxicity. Two
chromosome studies of potentially exposed workers were cited by these
authors. One study of eight accidentally sprayed field workers found damage
from the high toxaphene concentrations. Another study
of agriculture workers handling
toxaphene didn’t find injury from routine exposure. Simon and Manning point
to the inconsistency between the two field studies as proof there is
ambiguity over toxaphene and chromosome damage. However, field studies of
accidentally exposed workers are independent studies, not laboratory
controlled studies, and each type exists separate from the other. There are
no correlations within the studies between toxin dosages or between cohorts
(age, sex, size, diet, etc.). There are unequal sample sizes; and no control
on when and how chromosomes are derived from cells. Under these conditions
the parameters are all variables; thus, one study cannot be used to refute
the other, as Simon and Manning have done. Scientists have rules for
comparing data sets. Simon and Manning ignore those rules to reach the
conclusion they prefer.
Developmental Effects of Toxaphene
Both
in vitro
and in vivo
(laboratory studies using isolated cells or whole animals, respectively)
show that toxaphene causes developmental effects. There is no dispute among
scientists that toxaphene changes the way organ systems develop in growing
animals. Simon and Manning argue in section 2.1.2 of their paper that doses
that induce developmental effects in the laboratory can be used as a
not-to-exceed level for toxaphene in the environment. We could not figure
out, from the information provided, how they calculated safe dosages for
toxaphene using the literature cited in their article.
Toxaphene
and Cancer
Toxaphene is
carcinogenic. In
vivo studies show toxaphene causes
cancer in laboratory animals. It is interesting and significant that Simon
and Manning do not cite studies that show toxaphene is clearly carcinogenic.
We restate these findings here:
“Two long-term carcinogenicity bioassays with toxaphene have been performed
in rats and mice with both species showing a carcinogenic response.”
“A statistically significant dose-related increased incidence of thyroid
tumors (adenomas and carcinomas) was seen in both male and female rats.”
“A statistically significantly increased incidence of liver cancer in
treated animals was observed and was dose-related.”
The only question is
whether or not toxaphene also causes cancer in humans. Simon and Manning
offer no models or observations that disprove or prove a link between
toxaphene and human cancer. As already noted, toxaphene is mutagenic and,
therefore, the potential to cause the mutations that lead to cancer is a
possibility. Simon and Manning correctly note that toxaphene is a tumor
promoter. Numerous studies using a variety of tools show that toxaphene acts
to interrupt normal cellular communication, one definition of a tumor
promoter.
Simon and Manning
use data on breast cancer in Inuit women to support their model. The Inuit
live in the circumpolar region and have a diet high in fish stocks;
toxaphene is now found in fish tissues all over the earth.
Simon and Manning
incorrectly infer that levels of toxaphene congeners observed in more recent
times in the Inuit have always occurred. TT concentrations may have been
higher, or lower, in the past. Inuits may be more, or less, at risk than the
general population based on dietary, environmental, or genetic factors. That
the Inuits’ experience constitutes a proof of the authors’ model is an
extraordinary claim that requires extraordinary proof, and Simon and Manning
offer no proof at all.
∑3PC
Simon and Manning
chose three of the several hundred toxaphene compounds to base testing for
environmental toxaphene: p-26, p-50, and p-62. More data and field surveys
are needed to determine if these three compounds are indicative of dietary
fish residues. For aquatic food chain and rain deposition (atmospheric
reflux) these compounds may indeed prove useful for monitoring food stocks,
after more data has been collected and evaluated. However, to make the leap
from blood plasma levels caused by eating contaminated fish caught near the
Arctic Circle, to soil cleanups in the southeastern U.S., is scientifically
invalid.
We concur that the
logic of the approach has merit: there may be a set of TT congeners that are
especially indicative of the presence of TT in both TT standards and
weathered or off-grade materials. However, the three selected by Simon and
Manning are arbitrary at this junction when applied to soil cleanups; the
authors offer no data, nor is there any in the literature.
Over
the past dozen years, the Environmental Protection Agency's Office in Region
4, Atlanta, Georgia, has used an alternative method of testing. The
so-called Toxaphene Task Force alternative methodology employed a subset of
the toxaphene congeners occurring on a gas chromatograph. The EPA's Office
of Inspector General has reviewed toxaphene methods used in Region 4 and
found that the TTF method underreported toxaphene, and was not
representative of the state-of-the-art in environmental testing. Simon and
Manning’s three-congener method looks curiously similar to the discredited
TTF methodology. More science is
needed before any conclusions can be drawn.
Summary
It is not clear why
tumor promotion is offered as an endpoint driving chromatographic analysis
of samples. There is no controversy between experts regarding the
mutagenicity or carcinogenicity of toxaphene. Toxaphene is mutagenic.
Toxaphene causes cancer. Simon and Manning offer no argument for even
needing to rely on tumor promotion for a reference dose.
There is no belief
in the general scientific community that toxaphene is extraordinarily
difficult to measure. The EPA’s standardized Total Area method for measuring
multi-component pesticides works. Gas chromatography negative ion mass
spectroscopy works quite well.
Since there is no
technological need for toxaphene analysis based on only three components,
and no scientific rationale for using tumor promotion to drive that
analysis, Simon and Manning propose a solution to a problem that doesn’t
even exist.
The Simon and
Manning paper raises several issues related to analysis of environmental
toxaphene. Unfortunately, the authors generalize, speculate, and infer to
such a degree that meaningful conclusions cannot be drawn. One of greatest
dangers in research is to assume what one is trying to prove. Assuming at
the outset, that a particular conclusion should result, inevitably
introduces bias in the conclusions. Such bias is evident in the Simon and
Manning paper. The authors clearly state that just 3 of 800 toxaphene
congeners can be used to determine the safety of soil at any cleanup site
anywhere in the world.
“…continued use of the more stringent toxicity assessment for technical
toxaphene will result in inaccurate risk/hazard estimates and possibly
unnecessary and overly costly cleanups.”
(Section 4.3, last paragraph).
“More stringent
toxicity assessments” refers to practices advocated by the EPA’s Ombudsman.
The authors argue that these three congeners are predictive regardless of
the origin of the toxaphene, regardless of the form of environmental
degradation, regardless of any extraction or instrument bias. In the process
of selecting studies to support their view Simon and Manning ignored facts
that disagree with their model.
Studies on the Inuit
Indians do not exonerate TT as a potential source of carcinogenic chemicals.
At this time, the numerous studies showing increases in breast cancer and
other tumors in the Inuit have not been traced to a single source. Therefore, a
contribution by TT to the overall cancer rate cannot be overruled. Further,
this single endpoint cannot be the sole determining factor for soil cleanup
in North America. Superfund law is based on multiple criteria: meets all
laws; implementability; state acceptance, community acceptance; feasibility;
reduction in toxicity, mobility, or volume; and, overall health of humans
and the environment. Superfund criteria clearly state that it is the
overall health of humans and the environment, not just humans, that must be
considered. The authors have not shown that cleanup endpoints derived from
humans near the artic circle could be protective for other species in North
America. Without more hard physical data there is little difference between
using the Region 4 Environmental Protection Agency’s discredited Toxaphene
Task Force (TTF) methodology and the model described in their paper.
Finally, congener
“persistence” as an endpoint is fallacy. One can pick and choose references
to argue that some congeners are only present at key points in the onset of
a tumor as transient species. One can argue, using a subset of references,
that congeners below the limits of detection are influential in cancer
onset. However, to do either would be as invalid as Simon and Manning’s
flimsy thesis.
Conclusions and Recommendations
At this point in
time, it is very clear that lines are drawn between the Region 4 EPA and
practically everyone else regarding toxaphene analysis for the purposes of
cleaning sites in the southeastern USA. The EPA seems intent on using the
Toxaphene Task Force methodology, or its Simon and Manning clone. On the
other side are numerous environmentalists and academic scientists, with
similar credentials relative to the EPA, who argue current practices
underreport toxaphene. Finally, there is the EPA’s own Ombudsman who has
tried to find the best available science and apply it to this case; however,
in the years that the Office of Inspector General has been involved little
progress has been made. It appears Region 4 will continue to use some
variation of the discredited TTF method unless it can be shown, without
equivocation, by some third party, neither EPA nor environmentalist, that
the toxaphene measurement technology Region 4 is using cannot, and will not,
work.
We note that the
National Research Council of the National Academy of Sciences can perform
the studies needed to clarify toxaphene measurement in the environment. The
NRC has undertaken chemical-specific studies on asbestos, dioxin,
trichloroethylene (TCE), and on numerous other environmental issues.
Progress on cleaning the environment of toxaphene will not be made until
toxaphene is defined; debating that definition has become an endless
process. A third-party should be consulted and there is none more accepted
than the NRC. We recommend that the Glynn Environmental Coalition seek to
have a thorough review of toxaphene by a committee of the National Academy
of Sciences.
Written by R. Kevin Pegg, Ph.D.;
edited by Dr. Mary S. Saunders. Copies of the newsletter are available from
the GEC, at the Glynn County library, or at
www.enviro-issues.net
on the Internet.
Volume 15, Number 1,
August, 2006 |
P. O. Box 2443