L. Vandenburg, Phd. Letter to Water Control Board

The Tufts Center for Regenerative and Developmental Biology

200 Boston Ave Suite 4600, Medford MA 02155

Phone: 617-627-4094

email: Laura.Vandenberg@tufts.edu

June 27, 2012

Jeanine Townsend, Clerk to the Board
State Water Resources Control Board
1001 I Street, 24th floor
Sacramento, CA 95814

RE: Comment letter-Amendment to the Recycled Water Policy

Dear Members of the State Water Resources Control Board,

I am an academic scientist who has worked for nine years on issues related to endocrine
disruptors, including assessments of human exposures, meta-analyses of published literature,
and benchwork assessing the effects of chemicals on development, behavior, reproduction, and
other endpoints in rodents and aquatic animals. My PhD is in Cell, Molecular and
Developmental Biology, although my work is also well recognized in the field of Environmental
Health Science. I have published more than 25 peer-reviewed studies and two book chapters
and have served on expert scientific and risk assessment panels in the EU and the US. I was
also the lead author on the most comprehensive review to date on low dose exposures to
endocrine disrupting chemicals (EDCs; discussed in more detail below).

I am writing to challenge the assertion that “monitoring of individual CECs is not [necessary] for
recycled water used for landscape irrigation.” I encourage you to consider the extensive peerreviewed
scientific literature on the effects of low doses of EDCs before making decisions about
chemical safety in the water supply. Although your scientific board, and many toxicologists
around the world, conclude that “the dose makes the poison” when it comes to environmental
toxicants, this statement is simply not supported by fact when the chemical in question is a
hormone, hormone mimic, or hormone blocker.

In 2001-2002, the National Toxicology Program (NTP) addressed whether there was sufficient
evidence to conclude that EDCs act at low doses, i.e. at the doses that humans encounter in
their everyday lives. As you are likely well aware, humans encounter EDCs in their food, water,
air, dust, as well as household products like detergents, upholstery, solvents, etc. Although
typical humans are exposed to low levels of these chemicals (often in the nanogram per
kilogram body weight range), the US FDA has identified more than 1000 EDCs in current use, a
significant percentage of the over 80,000 chemicals currently in commerce (see
ult.htm). In 2002, the NTP addressed whether there was significant support in the scientific
literature for The Low Dose Hypothesis, the scientific hypothesis that EDCs could affect
development and reproduction of animals in the range that humans typically experience, i.e. the
low dose range. Although the NTP was hindered at that time by a relative paucity of data, they
did conclude that there was evidence for low dose effects for several EDCs including DES,
genistein, nonylphenol and methoxychlor [1].

In 2009, I began working with a group of 11 experts in the fields of endocrinology, cancer biology, ecology, developmental biology, and epidemiology on re-assessing scientific support for The Low Dose Hypothesis. These experts are at the forefront of their fields, have served on expert panels around the world, testified before the US Congress, and are collectively the authors of more than 1000 papers on environmental chemicals. Most of these scientists have been working on this issue for decades.

It took us three years to review over 800 published papers from the endocrinology and toxicology literature. Looking at this body of evidence as a whole, we concluded that there was clear and consistent evidence that a large number of EDCs have effects at low doses [2]. In fact, for every chemical where we could identify a low-dose cut-off and low dose studies had been performed, there were low dose effects. These chemicals include herbicides, insecticides, fungicides, preservatives, industrial chemicals, surfactants, plasticizers, pharmaceuticals, flame retardants and anti-bacterial agents, among others. We also identified hundreds of examples of non-monotonic dose response curves, i.e. those where the dose does not make the poison. Not only did we identify these types of responses in cultured cells and laboratory animals, but they were also observed in human populations. Our analysis indicates that low dose effects and non-monotonic dose responses are common for EDCs, and in fact may be the expected type of biological response for this large class of chemicals. Most importantly, we have a great understanding of the mechanisms behind these types of effects; hormones act in the body at exceedingly low concentrations, i.e. in the part per trillion or part per billion range. The endocrine system is tuned to respond to these low doses. Thus, low doses of chemicals that mimic hormones follow the same “rules” as the natural compounds. Additionally, while these low levels of hormones can have reversible actions in (i.e. an adult female taking pharmaceutical estrogens [birth control pills] will have reduced fertility due to ovulation inhibition, but cessation of pharmaceutical treatment restores her fertility), hormones are known to change the development and differentiation of tissues in embryos, fetuses, and even neonates. These effects will be permanent and irreversible. The concept of low dose effects and non-monotonic dose responses is not at the fringe of science. The Endocrine Society, the world’s largest professional association of clinical and research endocrinologists, has released two recent statements regarding EDCs, and has repeatedly reiterated the conclusion that low doses of EDCs are harmful to humans and wildlife [3, 4]. This conclusion has widespread acceptance in the field of endocrinology due to the strength of the published data. Additionally, following the publication of our review [2], Dr. Linda Birnbaum, Director of the National Institutes of Environmental Health Science (NIH) and one of the world’s leading toxicologists wrote an editorial stating: “the question is no longer whether nonmonotonic dose responses are ‘real’ and occur frequently enough to be a concern; clearly these are common phenomena with well-understood mechanisms…It is time to start the conversation between environmental health scientists, toxicologists, and risk assessors to determine how our understanding of low-dose effects and nonmonotonic dose responses influence the way risk assessments are performed for chemicals with endocrine-disrupting. Together, we can take appropriate actions to protect human and wildlife populations from these harmful chemicals and facilitate better regulatory decision making.” [5]

On page 13 of your revised policy, it is stated that “Regulatory requirements for recycled water shall be based on the best available peer-reviewed science.” The low dose literature that we reviewed in our recent analysis was all peer-reviewed science, and our analysis was peer reviewed as well. Yet this vast body of science has not been considered or addressed by the board. Thus, I respectfully ask this committee to reconsider suggestions that exposure of human and wildlife populations to EDCs, including pharmaceuticals, should not be concerning if the concentrations of these chemicals are “low”. Clearly, relying on the centuries old adage that “the dose makes the poison” is not sufficient to protect public health.




Laura Vandenburg, Phd.

Tufts University Center for Regenerative & Developmental Biology



References Cited

1. Melnick, R., et al., Summary of the National Toxicology Program’s report of the

endocrine disruptors low-dose peer review. Environ Health Perspect, 2002. 110(4): p.


2. Vandenberg, L.N., et al., Hormones and endocrine disrupting chemicals: low dose

effects and non-monotonic dose responses. Endocrine Reviews, 2012. 33(3): p. 378-


3. Diamanti-Kandarakis, E., et al., Endocrine-disrupting chemical: an Endocrine Society

scientific statement. Endocr Rev, 2009. 30: p. 293-342.

4. Zoeller, R.T., et al., Endocrine-disrupting chemicals and public health protection: a

statement of principles from the Endocrine Society. Endocrinology, 2012. Epub June

25, 2012: p. en.2012-1422.

5. Birnbaum, L.S., Environmental chemicals: evaluating low-dose effects. Environ Health

Perspect, 2012. 120(4): p. A143-4.