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Endocrine Studies



  • 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.”

» Information on EPA’s Endocrine Disruptor Screening Program

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 study published in 2006, Tomonari et al.1 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. A subsequent study by McKinnell et al.2 observed no adverse effects in the reproductive development of males born to pregnant marmosets exposed to high levels of DBP. 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.3 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.

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.

Understanding Endocrine Disruption

The endocrine (hormone) system regulates biological processes in mammals, birds, fish, and many other types of living organisms from conception through adulthood and into old age. These processes include the development of the brain and nervous system, growth and function of the reproductive system, metabolism, and blood sugar levels. The female ovaries, male testes, and pituitary, thyroid, and adrenal glands are major parts of the endocrine system.

Disruption of the endocrine system can occur in various ways. Some substances 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). Other endocrine disrupting substances block the effects of a hormone from certain receptors (e.g., growth hormones required for normal development). Still others directly stimulate or inhibit the endocrine system and cause overproduction or underproduction of hormones (e.g., an over or underactive thyroid).

Certain pharmaceutical drugs, such as birth control pills, are used to intentionally cause some of these effects. A number of plants (e.g., soybeans) produce substances that have been shown to affect hormone levels.

The concept of endocrine disruption encompasses both a hormone-based mechanism of action and an adverse health effect. Finding that a chemical may interact with a component of the endocrine system does not necessarily mean that an adverse effect will result. In addition, natural variations in hormone levels and reversible or transient changes in levels may occur that are not considered adverse. Mechanistic information alone is insufficient to evaluate the potential health significance of exposure to chemicals. Certain interactions or responses will be within the range of normal response and, therefore, are not considered adverse effects.

For more information, please visit: http://www.americanchemistry.com/endocrine.

A Wealth of Toxicity Data Already Exists

ACC member companies are committed to developing, producing, and putting into the marketplace products that are both beneficial and safe for humans and the environment. Accordingly, our members conduct science-based evaluations of a chemical’s efficacy and safety for its intended use.  

The Product Safety Code was developed by ACC and its member companies based on industry best practices to drive continuous improvement in chemical product safety, as part of the industry’s signature environmental, health, safety and security program. » Learn More

Although several of the specific Tier 1 tests under EPA’s Endocrine Disruptor Screening Program may not have been conducted on the five identified phthalates, a considerable amount of information already exists on these substances from traditional toxicity tests. These traditional tests assess potential health effects resulting from all mechanisms, including endocrine (hormone) pathways.

1 Tomonari, Y., Kurata, Y., Kawasuso, T., David, R., Gans, G., Tsuchitani, M., and Katoh, M. (2006). Effect of di(2-ethylhexyl) phthalate (DEHP) from juvenile common marmosets. Journal of Toxicology and Environmental Health, Part A, 69:1651-1672.
2 McKinnell, C., Mitchell, R.T., Walker, M., Morris, K., Kelnar, C.J., Wallace, W.H. and Sharpe, R.M. (2009). Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset. Human Reproduction, 24(9):2244-2254.
3 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.

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