- Phthalates are not synthetic hormones
- The potential effects of phthalates on the production of estrogens, androgens, and other hormones have been well studied and are the subject of numerous reviews
- A few phthalates have been found to interfere with normal sexual development in male rats at doses significantly higher than those typically experienced by humans
- These adverse effects have not been seen in monkeys and may not be relevant to human exposure.
The endocrine system in humans and other animals produces the hormones that regulate the body’s various processes, such as sleep, metabolism and reproduction, which are vital to the chemistry of life. One example of a hormone is insulin, which controls the level of sugar in our blood. Another is adrenalin, which helps us deal with stress or danger. Reproductive hormones impart sexual characteristics—estrogens are hormones that impart female characteristics and androgens are hormones that impart male characteristics.
Endocrine Disruption Screening
In recent years, scientists have suggested that environmental chemicals and some natural products like soy interfere with the production of hormones in humans and other animals. These products have been termed endocrine disruptors.
According to the Environmental Protection Agency (EPA), disruption of the endocrine system can occur when some chemicals “mimic a natural hormone, fooling the body into over responding to the stimulus (e.g., a growth hormone that results in increased muscle mass), or responding at inappropriate times (e.g., producing insulin when it is not needed).” Others “directly stimulate or inhibit the endocrine system and cause overproduction or underproduction of hormones (e.g., an over or underactive thyroid).” As EPA explains, however, how exposure to endocrine disruptors is linked to human diseases remains “poorly understood and scientifically controversial.”
The World Health Organization International Programme on Chemical Safety (WHO IPCS) conducted a global assessment of the state of the science relative to endocrine disruption. In its August 2002 report, the WHO IPCS stated that, “Analysis of the human data by itself, while generating concerns, has so far failed to provide firm evidence of direct causal associations between low-level (i.e., levels measured in the general population) exposure to chemicals with [endocrine disrupting effects] and adverse health outcomes.” The report concludes: “studies examining [endocrine disrupting chemical]-induced effects in humans have yielded inconsistent and inconclusive results, which is responsible for the overall data being classified as weak.” The report does point out, however, this classification “is not meant to downplay the potential effects of [endocrine disrupting chemicals]” and instead “highlights the need for more rigorous studies.”
In October 2009, EPA initiated an Endocrine Disruptor Screening Program to validate testing methods for effectively screening substances for endocrine effects that includes a list of 67 substances used in pesticides. As EPA notes, the list “should not be construed as a list of known or likely endocrine disruptors.” The European Union also has developed an initial list of candidate substances for “further evaluation” as potential endocrine disruptors developed by the European Union. This initial listing process represents only a first step in identifying compounds for further in-depth evaluation, and is not a list of known or likely endocrine disruptors.
Phthalates and the Endocrine System
Phthalates are not synthetic hormones, nor do they mimic estrogen or testosterone. The potential effects of phthalates on the production of estrogens and androgens have been well studied and are the subject of numerous reviews. While most of the phthalates in commerce are not associated with endocrine effects, a few phthalates have been found to interfere with normal sexual development in male rodents at doses 2,000 times higher than those typically experienced by humans—resulting from reduced testosterone synthesis. This effect is not seen in primates.
In a significant study published in 2006, Tomonari et al1 found that very high doses of DEHP administered to juvenile marmoset monkeys from weaning to sexual maturity had no negative effects on the development of the male reproductive tract. As marmosets are primates (i.e., closer to humans in both physiology and development than are rodents), the research indicates that the reproductive effects observed in rodents may not be relevant to humans.
A study published in 2004 may help explain the different reactions from species to species. In the study by Kessler, et al.,2 female rats and marmosets were fed equivalent doses of DEHP, and then tested for levels of MEHP, which is a major metabolite of DEHP. Blood levels of MEHP were as much as 7.5 times lower in the marmosets, and the total internal dose of MEHP was as much as 16 times lower. In other words, one reason primates appear to be less vulnerable to DEHP is that they experience lower internal doses at equivalent external exposures. They simply do not absorb the DEHP as efficiently as rodents, nor do they convert it as efficiently to MEHP.
Importantly, safety standards for chemicals (e.g. phthalates) that have been extensively tested for toxicity under a variety of statutes at the international, national, and state levels, already take into account the potential for adverse health effects, including effects that may be resulting from interactions with the endocrine/hormone system.
Human Studies
Several recent epidemiology studies have suggested an association between adverse effects in males and levels of the metabolites (break-down products) of a few phthalates in the urine. These findings, while of interest, have been considered of limited usefulness by the National Toxicology Program’s Center for the Evaluation of Risks to Human Reproduction and the Environmental Protection Agency’s National Center for Environmental Assessment because of concerns about the methodology and small sample size.
These studies also suffer from a lack of a third-party validation of the data and methodology. In fact, several could not be replicated by other researchers. In some cases, the authors derived a new statistic or new measurement index whose relevance has not been established. The authors further blur possible interpretation of their results by pooling data points into broad exposure categories prior to making their associations.
For More Information
Visit EPA's website to learn more about the human endocrine system and endocrine disruptors.
1 Tomonari Y., Kurata Y., Kawasuso T., David R., Gans G., Tsuchitani M., Katoh M. Effect of di(2-ethylhexyl) phthalate (DEHP) from juvenile common marmosets. Journal of Toxicology and Environmental Health, Part A, 69:1651-1672, 2006.
2 Kessler, W., Numtip, W., Grote, K., Csanady, G., Chahoud, I., and Filser, J. (2004). Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets. Toxicology and Applied Pharmacology, 195:142-153.
