Ulrich, EM, A Caperell-Grant, S-H Jung, RA Hites, and RM Bigsby. 2000.
Environmentally Relevant Xenoestrogen Tissue Concentrations Correlated
to Biological Responses in Mice. Environmental
Health Perspectives 108:973-977.
et al. report on experiments that demonstrate endocrine-disrupting
effects of DDT and HCH (hexachlorocyclohexane) in laboratory experiments
with mice. The most important aspect of their work is that
they found statistically significant responses to doses of these
two compounds comparable to background levels measured in
people living in the real world--that is, from people who had not
been exposed occupationally. This paper is an important addition
to the weight of evidence indicating that the old assumption of
toxicology--that background levels are benign--is no
longer a safe assumption.
is also worth bearing in mind that Ulrich et al. worked with
chronic exposures to adult mice on a reproductive tract outcome.
Neither their target animals nor their endpoint are likely to
be the most sensitive. In general, fetal development is a more
sensitive stage in life and neural/behavioral endpoints are more
sensitive than reproductive tract structural changes. This suggests
that studies comparable to Ulrich et al. of the impacts on
fetal exposure on behavior should be conducted. Fred vom Saal's
neurobehavioral work with methoxychlor is consistent with this interpretation.
Moreover, Ulrich et al. point out they may not have conducted
their experiments on the most estrogen-sensitive strain of mice.These
considerations suggests that careful study may reveal impacts at
even lower doses.
did they do?
et al. exposed adult female mice to chronic doses of DDT
and HCH over a wide range of doses. Both compounds are well-established
as endocrine disruptors. DDT binds competitively to the estrogen
receptor. HCH does not, but instead achieves estrogenic activity
through other mechanisms. Both are also both biaccumulative and
virtually ubiquitous. Ulrich et al. observe that "virtually
all humans have been exposed to these compounds."
chemicals were delivered via "leaky" implants placed subcutaneously
in the mice. The experimental protocol included both positive controls
(receiving estrone) and controls. Dose was varied over a wide range
of exposures, with the highest being 32x the lowest. Treatment continued
only for one week.
measured changes in the uterine (uterine epithelial height) and
vaginal structure (vaginal epithelial thickness) of the mice following
treatment and compared treated animals to the controls. They also
measured contamination levels in the fat and the blood serum of
did they find?
treated with DDT and HCH showed altered uterine and vaginal characteristics
in response to treatment. Because they measured contaminant levels
in the blood, they were able to establish the blood levels at which
effects were detected. "The lowest-observed-effect levels (LOELs)
in the vaginal response were detected at blood concentrations of
42 ng/mL and 18 ng/mL for ß-HCH and o,p´-DDT, respectively."
"Statistically significant increases in UEH <the uterine
response> were detected at blood concentrations of 66 ng/mL and
18 ng/mL for ß-HCH and o,p´-DDT, respectively"
does this mean?
Ulrich et al. actually measured the levels of DDT
and HCH in the blood in at the LOEL level, they are in a position
to compare this to typical human exposures. This is a highly
unusual aspect of the study and a reason for its great importance.
Most studies do not both vary the dose-delivered and measure
the blood and fat concentrations.
occupational exposure to DDT and HCH leads to blood levels of these
two compounds many times higher than the LOEL established by this
work. For example, they cite data from studies in Argentine pesticide
workers with HCH levels nearly 6 times the LOEL of this study.
greater interest is comparing these data to human exposures at background
levels (i.e., not of pesticide workers). They report that "the
concentrations of OC pesticides in different unexposed human populations
were generally only 2.7-120 (DDT) or 2-140 (HCH) times lower than
concentrations found to cause estrogenic responses in mice. However,
in Israel, o,p´-DDT blood concentrations were found to be as high
as 32 ng/mL (28), nearly double the minimal estrogenic blood level
of 18 ng/mL observed in this study.
et al. go on to comment: "Although it is difficult to
determine if the response in humans is the same as in mice, it
is alarming that the human blood concentrations are so similar
to the estrogenic concentrations in mice. The mouse has proven to
be a good model for approximating estrogenicity of a compound in
extremely low levels required to cause statistically significant
effects compared to control animals were unexpected. It is even
more alarming that there is little difference between these
levels and those that can be found in humans."
does one see the word "alarming" used in a scientific