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Environmental Exposures
 
Environmental Impacts on Reproductive Health

(Published January 2010)

The Links Between Environmental Exposures and Reproductive Health

This chapter explains how exposures to certain toxicants might result in adverse effects on reproductive health.

Environmental health has been defined as “the branch of public health that protects against the effects of environmental hazards that can adversely affect health or the ecological balances essential to human health and environmental quality.”1 As such, the field encompasses research, assessment, and guidance about the health effects of a variety of exposures in our environment, including radiation, chemicals, and some biological agents. This monograph focuses specifically on chemicals and heavy metals such as mercury that can have adverse effects on reproductive health.

Chemicals in the Environment

Of the 87,000 chemicals registered for commerce in the United States, only one-tenth have been tested for potential health effects.2,3 Of those that have been tested, only a portion have been assessed for reproductive health effects. Although many of these chemicals are integral components in the production of important materials and goods, some may adversely affect human health or the environment.

Testing of the chemicals used in the United States is limited by the fact that current legislation—the Toxic Substances Control Act (TSCA), which was passed in 1976—assumes that most chemicals are safe unless proven otherwise. These chemicals make up a large majority of the chemicals used in the United States today. Furthermore, many chemicals in common use—such as those in pesticides and many personal care products—are not regulated under TSCA.3 In addition, as a result of advances in toxicology, including better understanding of low-dose effects, many experts believe that the current regulatory methods for testing toxicity are no longer adequate.

Reproductive Trends in Some Geographic Areas Raise Concerns
  • Increase in testicular cancer incidence
  • Decreasing sperm counts
  • Decline in serum testosterone
  • Earlier pubertal development in girls
  • Fewer males being born
  • Documented increases in certain types of birth defects
Figure 1: Reproductive Trends in Some Geographic Areas Raise Concerns4-13

Concerns About Reproductive Health Effects

Over the past several decades, awareness has been growing regarding the reproductive health effects of exposures to certain chemicals. Scientists, clinicians, and patients have concerns about a number of recently identified trends in fertility and reproduction (see Figure 1). Some of these trends are localized to specific geographic locations; others are more widespread.

Given the history of the slow response to emerging data on toxicants, many scientists, clinicians, and advocates are concerned that delays in addressing exposures will occur again.14 Experience has demonstrated that waiting until firm “proof” is available can cause significant time lags between the point where there is knowledge of a link between health outcomes and exposure to an environmental toxicant and the time when regulatory action is taken or clear guidance provided. In the past, serious steps to prevent and mitigate some environmental threats to public health were taken only after decades of data were collected—and thousands of lives affected. For example, physicians did not counsel patients to avoid tobacco exposure until several decades after there were clear scientific data on the health effects of smoking. Lead, mercury, and asbestos are other examples of this unfortunate lesson. For this reason, many experts are fostering more widespread adoption of a precautionary, or preventive, approach.

As early as the 1970s scientists developed the concept of the precautionary principle, which states, “When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause-and-effect relationships are not fully established scientifically.”15 This principle provides a general approach to guide policy-making, patient counseling, and personal decision-making about environmental exposures. On the basis of currently available evidence, providers can take a precautionary approach and recommend actions to avoid exposures.

Impact on Reproductive Health

Reproductive toxicants may contribute to a spectrum of adverse effects on reproductive health. These effects include menstrual irregularities, early or delayed puberty, infertility, subfertility, early pregnancy loss, fetal death, impaired fetal growth, low birthweight, premature birth, and structural (e.g., cardiac defect) or functional (e.g., learning disability) birth defects.16,17 The impact of exposure to a reproductive toxicant may not be immediately evident. Instead, the effects may emerge at key life transitions: for example, when attempting conception, during pregnancy, during development of the embryo or fetus, in the newborn, and during the offspring’s childhood, puberty, and eventual fertility as an adult.18 For this reason, it is important to be aware of the potential effects of a substance over a long period of time, rather than only during the period immediately after exposure.

Exposure to Reproductive ToxicantsExposure to Reproductive Toxicants

Substances with potentially harmful effects on reproductive health are present in water, air, soil, dust, food, and consumer products. Individuals may encounter these toxicants in the home, community, school, or workplace. To result in an adverse effect, a toxicant must come into contact with an individual and enter the body, a step referred to as biologic uptake. Biologic uptake is the point at which exposure occurs (see Figure 2).

Toxicants enter the body in one or more of three ways: inhalation, ingestion, or absorption through the skin. After entering the body, toxicants are distributed to various tissues and subject to metabolism and excretion. Toxicants, or their metabolites, travel to target organs, such as the thyroid, ovaries, or testes, where they exert biological effects.19 Some toxicants can be stored for long periods of time in muscle, bones, adipose tissue, or other soft tissues. For example, lead can reside in bone for decades. These substances are described as having long “half-lives” within the body. They can continue to leach from these tissues and travel to target organs for long periods of time.

In the same way that all smokers do not develop lung cancer, every person exposed to toxicants does not necessarily experience adverse health effects. Many factors—in addition to the exposure dose and the concentration of toxicant in the environment—affect whether an exposure ultimately results in a harmful health effect.19 These factors, which are listed in Figure 3, can directly influence cells, tissues, and organs, and they can alter gene function or expression.Environmental Factors That Influence the Effects of Toxicants

Whether or not an environmental exposure results in adverse effects on reproductive health in an individual ultimately depends on the interaction among these various factors. For this reason, it is often impossible to document a clear tie between a specific toxicant and a specific reproductive health effect.

“Safe” Levels

Environmental experts now are challenging the traditional assumptions about “safe” levels of toxicant exposures at a population level. Recently, the National Academy of Sciences stated that based on the extent of multiple chemical exposures individuals experience, disease frequency, age status of the population, and genetic variability, it is reasonable to assume that exposures to certain chemicals will carry some risk, though that risk may be small or large.20 At present, it can be challenging to quantify the risk because traditional testing of chemicals—using high doses in adult animals, often with little genetic or other variability—makes it difficult to predict precisely the effects of everyday exposures.14 For this reason, it is difficult to create clear clinical guidance that addresses the potential health effects of lower levels of exposures, which are more common in the general population. It is important for clinicians to recognize that some occupational exposures to hazardous chemicals are substantially higher than those for the general population.

Timing of Exposure

The timing of exposure is another factor that strongly influences the ultimate biological effect of exposure to environmental toxicants. Although exposure to these substances can affect individuals at all stages of life, exposure during critical windows of susceptibility may have more significance. These windows vary somewhat depending on the particular toxicant and include periods during gestation, childhood, adolescence, and adulthood. Because these windows of susceptibility include very early pregnancy, clinicians should counsel women about exposures throughout their reproductive lives.

Mechanisms of Effects

Some chemicals have direct toxic effects on the reproductive system. Endocrine-disrupting chemicals (EDCs) can exert effects on hormone-producing glands, such as the thyroid or pituitary, which in turn affect reproductive health. EDCs also may have direct effects on the reproductive system.

Toxicants can exert negative reproductive effects through several mechanisms, as shown in Figure 4.21 Some chemicals kill or damage cells. If these cells are oocytes or sperm cells, exposure to the chemicals can result in infertility. If they are other types of cells, developmental problems can occur. For example, the anti-seizure drug phenytoin causes birth defects by disrupting normal embryonic and fetal development without causing mutations in DNA.16,22 Other chemicals alter the structure of DNA, causing gene mutations.21 Depending on the genes affected, mutations can result in an inability to conceive or in birth defects in the offspring. Some chemotherapeutic agents cause DNA mutations. Some industrial chemicals, such as benzene, also are mutagenic. Finally, some chemicals, such as diethylstilbestrol (DES), cause an epigenetic effect: they change the way in which genes are expressed, which can affect reproductive outcomes.

Environmental Effects Have Multiple Mechanisms

Polychlorinated Biphenyls (PCBs) and Diethylstilbestrol (DES):
Well-Known Examples of Endocrine-Disrupting Chemicals

Table 2: Lessons Learned from PCBs18
Examples of potential effects:
  • Altered neurodevelopment as a result of in utero exposure
  • Endometriosis
  • Reduced fertility
  • Decreased semen quality
  • Miscarriage
  • Altered pubertal development
  • Reproductive tract malformations
PCBs were used as coolants and lubricants in electrical equipment before their use was banned in 1977.14,18 Today, the main source of exposure to PCBs is food contamination. PCBs first entered the air, water, and soil through manufacture, use, and disposal. They may still be released into the environment today from hazardous waste sites or the burning of certain wastes in incinerators. Because PCBs do not break down readily, they remain in the environment for many years. They are taken up by small organisms in water and then accumulate in the fish that eat these organisms, in some cases reaching levels thousands of times higher than that found in the water.23 Exposure and human levels of PCBs have decreased since 1977 and have recently leveled off. PCB exposure is a matter of concern because it has been linked to both reproductive effects, including menstrual disturbances in women and reduced fertility in men, as well as developmental effects, such as reduced birthweight.24 Table 2 lists the many potential reproductive effects of PCBs.

DES is an example of an endocrine-disrupting chemical that causes delayed, rather than relatively immediate, effects on reproduction.25-29 From the 1930s to the 1970s, the synthetic estrogen DES was prescribed to pregnant women in the mistaken belief that the drug would prevent miscarriage. Later, researchers learned that the drug actually increases the risk of miscarriage and other pregnancy complications (see Figure 5). In addition, the drug causes reproductive health abnormalities and reproductive tract malignancies in the children of women exposed during pregnancy. Animal studies suggest that grandchildren also may be affected.17

Women who took DES while pregnant

A later chapter addresses bisphenol A, another EDC, in detail.

References:

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  3. US Environmental Protection Agency. What is the TSCA Chemical Substances Inventory? 
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