Susceptible Populations

Endocrine systems of the body are responsible for regulating many intricate physiological processes. Substances which interact with the endocrine system can potentially have profound effects on health. Whether or not there are health effects may depend on the gender and stage of development of the individual and the dose and potency of the substance.

Fetal Development
Fetal development may represent a period of increased sensitivity to chemical insult due to the dynamic processes of growth and maturation which occur during this time. The different stages of development of the fetus are referred to as critical windows of development and include; cell proliferation in developing organs; cell migration; and development of specialized function. Disruptions to the intricate hormonal regulation of these processes can result in long-term irreversible programming changes which may lead to the occurrence of disease, such as cancer, later in life. If there is chemical insult at sufficient dosage during these sensitive windows of development, irreversible organizational effects can occur which may lead to effects on sexual differentiation, as well as on the maturing immune system and neuro-endocrine system. To date, there are no known cause and effect outcomes affecting human fetal development that scientists agree have come from low level, environmentally relevant exposures to endocrine active compounds but there are several proven relationships in experimental animals.

Children
Children may also be vulnerable to the effects of chemical exposures. There are a number of differences in physiological and metabolic processes between children and adults that can influence exposure and response. Differences in absorption rates, distribution patterns and some metabolic pathways in pediatric populations can influence the effective dose of a compound, subsequently determining its toxicity and effects.

These differences arise as a result of maturing organ systems which have not yet developed to full capacity, as well as other physiological differences which influence the movement of the chemical throughout the body. In addition there are important differences in exposure circumstances between adults and children. Compared to adults, children ingest more food, drink more water, and breathe more air per pound of body weight.

Behavioral practices of young children, including play close to the ground, increase the likelihood of exposure to contaminants in dust and soil. Children also frequently engage in hand-to-mouth behaviour, and are likely to put objects which have come into contact with the ground (such as toys) into their mouths. Breast-milk constitutes an additional unique route of exposure for children. Endocrine active compounds derived from the diet can accumulate in fat stores and are subsequently secreted in breast milk. If there is chemical insult at sufficient dosage during childhood to an endocrine active substance with sufficient potency, adverse effects could occur that influence growth patterns, neurodevelopment, and puberty. To date, there are no known cause and effect outcomes in children that scientists agree have come from low level, environmentally relevant exposures to endocrine active compounds but there are several proven relationships in experimental animals.

Adults
Individuals in their fertile years comprise another potential susceptible subpopulation, both males and females are vulnerable to impairment of reproductive function following exposure to endocrine active compounds, if the exposure is of a sufficient magnitude and the substance is of sufficient potency.

Women

The menstrual cycle is highly regulated through the interactions of several hormones and physiological responses. Interference of these hormonal signals can lead to abnormalities in the growth and development of the egg prior to its release from the ovary, or failure of the egg to be released from the follicle. These changes in the normal process of ovulation can lead to infertility. Disruption of the hormonal regulation of the menstrual cycle has also been associated with the development of endometriosis. The contraceptive pill acts through the hormone system of females, and is in a sense a form of endocrine disruption. In terms of adverse effects in females, the overall weight of the scientific evidence does not support a connection between exposures to low level, environmentally relevant doses of endocrine active compounds and breast cancer, endometrial cancer or ovarian cancer. However, there has been little epidemiologic research of adequate quality on this issue and the potential for effects of low-level environmental contaminants remains an important research issue.

Men
Males are also at risk of developing reproductive abnormalities due to the dynamic process of sperm production. Spermatogenesis involves a series of signaling mechanisms which is regulated through the brain-pituitary-gonad axis. Sperm is constantly being produced and therefore these developing cells are theoretically susceptible to endocrine disrupting events. If there is chemical insult at sufficient dosage to an endocrine active substance with sufficient potency, adverse effects could occur that influence sperm production, sperm motility or sperm morphology. In terms of adverse effects in males, the overall weight of the scientific evidence does not support a connection between exposures to low level, environmentally relevant doses of endocrine active compounds and changes in sperm count. Although some scientists have theorized that exposure to endocrine active compounds may be associated with increases in testicular cancer, a clear cause and effect relationship has not been established, and research continues to evaluate a wide range of potential risk factors.

Men and women who are occupational exposed to endocrine active compounds may be the subset of the adult population that experiences the highest degree of exposures. Some of the occupations which have been postulated to be associated with relatively higher exposures to potential endocrine active compounds include agricultural workers, workers in the plastics industry, painters, hairdressers, laboratory workers, textile workers and cleaners.

In summary, endocrine active chemicals have the potential to cause a variety of adverse health effects. Lessons learned from birth defects resulting from exposures to DES, thalidomide, alcohol and cocaine demonstrate that the fetal period represents a critical window of development that is susceptible to environmental modulation. As with all cause and effect relationships, however, the dose of the chemical, duration and timing of exposure and the biological plausibility of the mechanism of action are important factors in assessing a relationship between chemical exposure and adverse health outcome. To date, the overall weight of the scientific evidence does not support a connection between exposures to low level, environmentally relevant doses of endocrine active compounds and adverse effects in humans. On a theoretical basis, the type and severity of effects would be dependent on the specific timing of exposure relative to the developmental stage of the individual, gender and the dose and potency of the substance.