Slama et al. (2016) recently published a paper on issues
relevant to setting regulations for endocrine disrupting substances in the
European Union.1 The authors discuss
options associated with these issues, briefly described as use of interim
criteria, or use of the World Health Organization definition of endocrine
disruption by itself or with additional categories of strength of evidence or
chemical potency.
We agree with several points of the authors, but we also
found some errors. The European Union is
said to be the first major authority to develop a strategy for the regulation
of endocrine disrupting chemicals. Not
so. The U.S. Environmental Protection
Agency (1980)2 and the World Health
Organization,3 developed strategies
for defining “safe” doses for chemicals
on the basis of reviewing data and applying factors 30 or so years earlier to
account for uncertainty in what those data tell us. The strategy, still in
force and still evolving,4 protects
against the adverse effect a chemical produces at the lowest level of exposure
and all other effects that the chemical may cause at higher exposure. Using this strategy, numerous chemicals have
been regulated with “safe” doses based on endocrine disruption, as can be seen
in a review of the International Toxicity Estimates for Risk (ITER) or the
Integrated Risk Information System (IRIS) on the U.S. National Library of
Medicine’s Toxnet web database.5 Thus,
endocrine disruption is not a new kind of hazard as the authors say, and as
already mentioned.6
The authors also state that potency of a chemical “is not
well defined,” and then go on to show in a series of figures why potency is not
helpful in an evaluation of endocrine disruption. But potency, the strength of a chemical in
causing its effects, is actually well defined in numerous toxicology
textbooks,7 and simple examples can be
easily shown to discount their concern.
For example, consider the chemicals perchlorate and
dihydrogen monoxide. These chemicals are
both disruptors of different endocrine systems, but they differ greatly in
potency or strength of effect.
Perchlorate disrupts thyroid hormones at tiny doses, ug/kg body
weight-day (essentially 1 sugar grain per day from a 1gram sugar packet). In huge contrast, dihydrogen monoxide
disrupts kidney and adrenal hormones at grams/kg body weight-day (essentially 5
to 7 quarts per day). So if potency is
not considered in the evaluation of these two chemicals for endocrine disruption,
how does one make a distinction in managing their potential risk?
Slama et al. might suggest that it does not make any
difference, or that a distinction should be made on what is considered to be
negligible exposure. This latter choice won’t work, however, as daily exposure
to dihydrogen monoxide is enormous (one to two quarts per day), whereas for
perchlorate the exposure is virtually zero.
Many authorities regulate perchlorate, the thyroid disrupting chemical
with extremely low, near zero exposure, but do not regulate water, (that is,
dihydrogen monoxide), for disrupting kidney and adrenal hormones.
The authors’ call for additional research is reasonable, but
funding of such research needs to be scientifically based. The current strategy focuses on determining
safe doses of chemical, including doses that would protect against endocrine
disruption. The challenge of current findings on endocrine disruption is to
assure that such protection is occurring.
This article was written in collaboration with several
authors: Dr. Michael Dourson, Dr. Sam
Kacew, Dr. Rita Schoeny, Dr. Wallace Hayes, Dr. Penny Fenner-Crisp, and Dr. Ray
York.
1 Rémy Slama, Jean-Pierre Bourguignon, Barbara Demeneix, Richard Ivell,
Giancarlo Panzica, Andreas Kortenkamp, and Thomas Zoeller. 2016. Scientific
issues relevant to setting regulatory criteria to identify endocrine disrupting
substances in the European Union.
Environmental Health Perspectives. Doi.org/10.1289/EHP217.
2 U.S. EPA (U.S.
Environmental Protection Agency).
1980. Guidelines and methodology
used in the preparation of health effects assessment chapters of the consent
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3 See, for
example: https://en.wikipedia.org/wiki/Acceptable_daily_intake.
4 A partial list
of references includes:
Barnes, D.G. and M.L. Dourson.
1988. Reference dose (RfD): Description
and use in health risk assessments.
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471-486.
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AR, Doe JE, Heinrich-Hirsch B, Meek ME, Munn S, Ruchirawat M, Schlatter J, Seed
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M.L., L.A. Knauf, and J.C. Swartout. 1992. On Reference Dose (RfD) and Its
Underlying Toxicity Data Base. Toxicology and Industrial Health. 8(3): 171-189.
Dourson,
M.L., S.P. Felter, and D. Robinson. 1996.
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Dourson,
M.L., G. Charnley, and R. Scheuplein. 2002. Differential
Sensitivity of Children and Adults to Chemical Toxicity: II. Risk
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Elder,
L., Poirier, K. Dourson, M., Kleiner, J., Mileson, B., Nordmann, H., Renwick,
A., Slob, W., Walton, K., and G. Wurtzen.
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quantitative methods. Food and Chem.
Toxicol. 40: 283-326.
IPCS
(International Programme on Chemical Safety). 2005. Chemical-specific adjustment factors for Interspecies
differences and human variability: Guidance document for use of data in
dose/concentration-response assessment. Geneva Swittzerland. Available at
www.who.int/ipcs/methods/harmonization/areas/uncertainty/en/index.html
M.
E. (Bette) Meek, Christine M. Palermo, Ammie N. Bachman, Colin M. North and R.
Jeffrey Lewis. 2013. Mode of action human relevance (species
concordance) framework: Evolution of the Bradford Hill considerations and
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5 See http://toxnet.nlm.nih.gov.
6 Herman Autrup,
Frank A. Barile, Bas J. Blaauboer, Gisela H. Degen,Wolfgang Dekant, Daniel
Dietrich, Jose L. Domingo, Gio Batta Gori, Helmuth Greim, Jan G. Hengstler, Sam
Kacew, Hans Marquardt, Olavi Pelkonen, Kai Savolainen, and Nico P.
Vermeulen. 2015. Principles of Pharmacology and Toxicology
Also Govern Effects of Chemicals on the Endocrine System. TOXICOLOGICAL SCIENCES, 1–5.
7 See, for
example, Cassarett and Doull, 1996, page 25, and all subsequent editions.
