TAG reports: Volume 2, Number 1;
January, 1993
009 Superfund Site: Community Concerns Over Toxaphene
Overview
During the December 12 meeting at the Beverly Shores Church in Glynn County, residents
expressed skepticism over views stated in the booklet Facts About Toxaphene. In this
pamphlet Hercules interprets existing data to imply that toxaphene is safe for human
exposure. Chemical testing for safety on humans is an indirect science. Most of what we
know comes from studies on animals, plants or bacteria. Consequently, there are few
"facts" available for toxaphene. The Coalition requested this review to aid
residents in understanding chemical toxicity. Carl Blair of the Agency for Toxic
Substances and Disease Registry and Dr. Marshall Steinberg of Hercules Incorporated
generously provided information for this newsletter. Additional references were from the
authors independent search of environmental databases.
An overview of toxaphene toxicology
Chemicals interact with living tissues to cause both benefit and injury. Some chemicals
produce mutations leading to cancer while other chemicals will inhibit tumor growth.
Chemicals may damage the immune system or act as antibiotics and aid the body's defense
mechanisms. One chemical may damage the liver or kidneys while another may be essential
for proper function. Often a chemical may be a lethal poison to one form of life and
safely tolerated by another. Finally, a chemical may have no effect at one stage of
development and inhibit growth at an earlier or later stage of life. Scientists consider a
chemical safe when testing on all tissues, at all life stages, in an assortment of animals
and plants shows little or no toxicity. Also, since individual members of a population
have a range of chemical sensitivity the number of animals tested must be large enough to
see subtle effects.
Chemical toxicity tests generally fall into the categories of genetic or physiological
assays. Genetic tests measure damage to DNA, the chemical "blue print" used by
all living cells for instructions on proper growth and function. Physiological assays
measure the ability of a chemical to interfere with metabolism. Chemicals that damage DNA
(called mutagens) may not have an effect for decades after exposure. Chemicals that
interfere with the metabolic functions of a cell are poisons and their effects appear
during the exposure period. DNA encodes instructions for growth and development in
structures called genes. Gene damage (termed "mutation") results in impaired
cell function. Bacteria are simple one-celled life forms that are very sensitive to DNA
damaging chemicals since they lack the complex repair systems and duplicate gene copies of
higher organisms. Consequently, single mutations in bacteria cause immediate injury while
in humans damage to several similar genes is required before the injury appears. Some
bacteria tests use strains designed to only grow after a mutation occurs. These tests
allow easy assay of genetic injury since growth only occurs in the presence of mutagenic
chemicals. A widely accepted bacterial test for detecting DNA damage, the Ames test,
clearly proves that toxaphene is mutagenic. Furthermore, studies using the Ames test show
toxaphene as a direct mutagen that does not require metabolic activation (some chemicals,
such as benzene, require activation by the animal's liver before becoming mutagens). Since
toxaphene is a direct mutagen it is likely to be mutagenic in all bacteria, plants and
animals.
Higher cells, such as those of humans, grow by a process of cell division called mitosis.
The cell nucleus contains the DNA of higher cells. During mitosis the nucleus transforms
into bodies called chromosomes that are easily seen with a microscope. Damage to DNA often
results in chromosome injury (termed aberrations). Aberrations are viewed as changes in
the appearance of normal chromosomes. Most chromosomes are "V" or "X"
shaped, having either 2 or 4 chromosome arms. A break occurs when a normally X-shaped
chromosome with four chromosome arms appears with only three and a half arms. When a
chromosome break occurs, genes are lost from the cell, impairing normal cell function.
Chromosome changes often are used to detect genetic disease. Some forms of Down's syndrome
result from changes in the arms of chromosome 21 (humans have 46 chromosomes). Changes in
chromosome 9 and 22 cause leukemia. In fact, damage to chromosomes is strongly linked with
cancer. Toxaphene has caused chromosome aberrations in accidently exposed human
workers(1).
Cancer is not well understood at this time, but mutation is necessary for cancer. In
higher life forms cells are organized into tissues and tissues into organs. The tissues of
a person's liver or skin have very distinct structure and functions, but the same DNA
"blue print" produced both cell types. Cancer occurs when the cells of a tissue
lose their normal function and grow out of control. A tumor is the result of a cancerous
growth. Most models for cancer require several mutations to occur before a cell becomes
cancerous. However, not all mutations result in cancer. Mutations that occur in DNA not
used in a particular tissue are usually "silent" mutations. As a result most
carcinogens target specific organs. In the case of toxaphene the target organ appears to
be the liver.
Laboratory studies on rats, hamsters and mice indicate that toxaphene caused cancer in the
livers of all animals studied(2). These studies are often criticized for their lack of
depth and poor controls. In most cases too few test animals were used to determine the
range of carcinogenicity of toxaphene. For example, one study using mice tested only about
50 animals for each study group consisting of a control group lacking toxaphene and low
and high dosages(3). The researchers called only the highest group "statistically
significant" in the amount of animals having liver tumors. But the small sample sizes
do not allow conclusions about the range of effect. The low dosage group showed a slight
increase in tumors compared to the controls, but the researchers did not consider the
increase statistically significant. If more animals were used it is likely that the group
would be significant as well. EPA standards call an excess cancer risk of 1 in 1,000,000
as significant. For these mice studies the excess cancer risk was considered significant
at about 1 in 10. In other words, the researchers used standards hundreds of times more
lenient than the accepted systems, thereby concluding that toxaphene was "safer"
than it actually may be. Also, using more animals in the study may reveal increases in
other cancer types missed because of the very small sample sizes. Finally, the control
group of the study had a high number of tumors, which is unusual for an untreated group,
and would decrease the chance of statistically proving carcinogenicity.
Virtually all the studies done on toxaphene showed these types of data problems. Even
thesingle human study conducted only surveyed two hundred people. Some of the individuals
were only exposed for 6 months. None were followed for longer than the study period.
Further, the study group was biased towards healthy male workers averaging about 35 years
of age. Data is lacking for potentially sensitive groups of exposed children, women or
elderly. The experimental format would probably not detect effects of well-known
carcinogens such as radiation or tobacco products.
Laboratory studies were conducted to determine toxaphene's effect on developing animals.
In vivo assays (tests done on whole animals) indicate toxaphene is not embryotoxic. It
does not kill a developing fetus. Neither was toxaphene implicated in serious fetal
defects (teratogenic). However, toxaphene does cause some types of bone malformations when
given in the drinking water of pregnant rodents. Studies on ducks also showed that
toxaphene impairs bone development of female hatchlings when the mother was fed
toxaphene(4).
In vitro testing presents a different picture of toxaphene's effect on development. In
vitro tests are done by exposing the fetus directly to toxaphene, rather than by exposing
the mother. Depending on the test format used toxaphene was both embryotoxic and
teratogenic(5,6).
One area of concern is the tendency of newborn mice to have a slowly responding immune
system(7). The immune system is the body's natural defense mechanism against infection.
Toxaphene delayed the immune response of treated mice as compared to unexposed control
animals.
Toxaphene probably causes few birth defects in mice and rats because the chemical does not
dissolve easily and therefore is unable to pass through the uterine wall to the fetal
environment of the womb. However, it is difficult to gauge toxaphene's effect on humans
based on research with animals. The long human fetal growth period of 9 months, compared
to about 3 weeks for a rodent, suggests there is a greater chance of toxaphene
accumulation in the developing human fetus (human gestation is about 1,200% longer than
rodents). There may also be "synergistic" (combination) effects occuring in
human populations. Certain diets and drugs alter movements of chemicals between the mother
and fetus. For instance, maternal infections, stress, alcohol, tobacco products and
aspirin all affect the fetal environment. No data is yet available concerning the complex
aspects of human pregnancy and environmental mutagens.
The primary result of toxaphene exposure in in vivo laboratory testing was liver damage.
The liver performs a detoxification role in the body. Toxaphene exposed animals all showed
enlarged livers. Harmless chemicals pass from the body of animals through the kidneys
(urine) or colon (feces). Some fat soluble chemicals accumulate in adipose tissue (vitamin
A, for instance) without undo burden on the body. However, changes in the liver indicate
detoxification of a harmful chemical. The liver is capable of producing enzymes that
destroy toxins. An increase in liver size and activity is a good indication that the
animal is attempting to cope with an environmental challenge. Toxaphene is particularly
well known to bioaccumulate in living tissue. Enlarged livers and liver cancer indicates
that toxaphene accumulates in body organs with potential for major organ damage. Toxaphene
injury is not confined to the liver. Injury to the kidneys and thyroid are also
reported(8). No data exists for toxaphene effects on primates related to man, such as
monkey or chimpanzee. Also no data is available on the molecular mechanism for toxaphene
carcinogenicity.
Information on toxaphene's health effects is poor at best. There are no long term studies
that would allow epidemiologists to conclude that toxaphene is safe for human exposure.
What studies are available are controversial because of poor design.
The existing data strongly supports the EPA's decision to ban toxaphene. The chemical has
a long environmental fate with proven mutagenicity and carcinogenicity. Toxaphenes
potential danger to human health and the environment far outweighs its usefulness in
insect control.
1 Samosh et al. 1974. Tsitol. Gen. 8:24.
2 Reuber, M.D. 1979.J. of Toxicol. and Environ. Health. 5: 729
3 National Cancer Institute. 1979. DHEW 79-837
4 Mehrle et al. 1979. Pestic. Biochem. Physiol. 10:168
5 Dunachie et al. 1969. Ann. Appl. Biol. 64:409
6 Saunder. 1980. Ecol. Res. Ser. EPA-600/3-80-006
7 Allen et al. 1983. J. Toxicol. Environ. Health. 11:61
8 Chu et al. 1988. J. Environ. Sci. Health. B23:101.
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