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Reproductive and Developmental Hazard Management Guidance: ACOEM Task Force on Reproductive Toxicology

Journal of Occupational and Environmental Medicine: August 2011 - Volume 53 - Issue 8 - p 941–949
doi: 10.1097/JOM.0b013e318229a549
ACOEM GUIDANCE STATEMENT
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EXECUTIVE SUMMARY

This guidance article was developed by the American College of Occupational and Environmental Medicine (ACOEM) to provide occupational and environmental medicine physicians, other health care professionals, labor, and management with a framework for evaluating and managing potential occupational reproductive and developmental health hazards. Several clinical scenarios that may be encountered by occupational and environmental medicine professionals are discussed. A multidisciplinary approach may be required to assess each workplace for potential reproductive and developmental hazards and implement appropriate responses for managing such hazards.

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BACKGROUND/INTRODUCTION

The magnitude of occupational and environmental reproductive and developmental health risks in modern society is still being studied. Scientific, epidemiological, and toxicological data concerning the reproductive and developmental health risks have been determined for some chemicals, but data on many chemicals, physical agents, and biological agents are limited and in some instances, nonexistent. Consequently, there may be considerable uncertainty about what action should be taken to adequately manage potential workplace reproductive health hazards.

Industrial exposure limits for most chemical agents promulgated by the Occupational Safety and Health Act (OSH Act), that is, permissible exposure limits, or the American Conference of Governmental Industrial Hygienists, that is, threshold limit values, have in most cases been established without considering protection from adverse reproductive or developmental health effects. Therefore, compliance with Occupational Safety and Health Administration (OSHA) exposure limits for many compounds may not ensure protection of reproductive health. Employees have the right to know about potential reproductive health hazards encountered in the workplace and the right to work in an environment that is free of significant reproductive health risks.

Reproductive toxicity is the occurrence of adverse effects on the reproductive system that may result from exposure to toxins or environmental agents. Toxicity includes alterations to the reproductive organs and/or the related endocrine system. Developmental toxicity can be defined as “the occurrence of adverse effects on the developing organism that may result from exposure before conception (either parent), during prenatal development, or postnatal to the time of sexual maturation. Adverse developmental effects may be detected at any point in the life span of the organism.”1,2 Developmental toxicity can include fetal death, structural abnormalities or birth defects, functional deficiencies, or altered growth.

Some women have been excluded from jobs that involved occupational exposure to known reproductive toxicants. In the United States, all-encompassing “fetal protection policies” that categorically exclude large classes of workers are illegal and work restrictions should be based on an individualized risk assessment for each employee. Policies aimed at reducing occupational exposure to potential reproductive developmental hazards should be based on individualized assessments and avoid gender discrimination.

ACOEM has developed this guidance document to assist occupational health professionals in managing reproductive and developmental risks, and uncertainties. This guidance describes measures to assess the magnitude of potential reproductive and developmental risks in the workplace and presents options to manage the uncertainty associated with these risks.

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Magnitude of Workplace Reproductive Health Problems

The number of women in the workplace increased from 30 million in 1970 to more than 67 million in 2007,3 and while an evaluation for potential reproductive toxicity has been required for pesticides and therapeutic drugs, few industrial agents have been tested for reproductive toxicity. There are no reliable estimates concerning the number of either male or female workers who are at significant risk of exposure to reproductive toxicants.4 There are several reasons for this lack of reliable information about reproductive hazards for industrial exposures, including limited epidemiological and toxicological data.

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Epidemiological Data

Epidemiological studies involving reproductive hazards are difficult to perform for several reasons. Reproductive toxicity endpoints are often difficult to measure. For example, spontaneous abortions commonly occur among the general population and some studies suggest that up to 40% of conceptuses undergo spontaneous abortion prior to the first missed menstrual period.5 Consequently, spontaneous abortion (miscarriage) can occur without a woman's knowledge, making monitoring of this endpoint difficult. Some adverse reproductive outcomes are rare and large sample sizes are necessary for a study to have sufficient power. For example, congenital malformations are diagnosed in approximately 3% of all births and large populations are required for an epidemiological study to have sufficient power to detect a difference between outcomes in exposed and nonexposed groups.6

Reproductive studies can be confounded by multiple factors. Maternal age is associated with several birth abnormalities and diminished fertility, which also may be due to exposure to chemicals in the workplace. Persons with lengthy occupational histories will also be older. Other confounding factors, such as sexually transmitted infections, sexual activity, and nutritional status may be difficult to adjust for in statistical analyses. Other factors that can affect fertility, such as smoking, alcohol, medication and drug use, general health, and socioeconomic status, can be more readily adjusted for in analyses. Finally, there can be uncertainty regarding the significance of the factor being measured. For example, there is scientific debate regarding the significance of variations in reproductive hormone concentrations or semen parameters within the normal ranges.

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Overview of Reproductive Physiology

Human reproduction involves multiple processes, all of which must proceed normally and occur at precise times. These processes include the normal maturation of male and female gametes (spermatozoa and oocytes, respectively), fertilization, implantation, embryonic and fetal development, birth, lactation, and postnatal development. During adult life, reproductive function in both men and women declines with age7; this is more apparent in women for whom the complete cessation of ovulation and fertility occurs at menopause. Data from the US National Center for Health Statistics National Survey on Family Growth show that about 5% to 7% of 15 to 29 year old, married, nonsurgically sterilized women are infertile, compared with 20% to 27% of 40 to 44 year old women.8,9

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Gamete Formation

Spermatogenesis is the process in which spermatozoa are formed and mature within the testis and epididymis for potential fertilization of an ovum. Oogenesis is the process in which an oocyte develops and matures within the ovary for follicular release at ovulation and potential fertilization by a spermatozoon. There are important similarities and differences between the two processes that affect their susceptibility to disruption by toxicants. Both processes begin during embryonic development and both processes are dependent on a functioning neuroendocrine system. Both processes involve the formation of a haploid gamete from a diploid precursor via meiosis. In the male, the precursor cells are called spermatogonia, in the female, oogonia. Oogonia and spermatogonia and the cells descended from them are called germ cells, as distinguished from somatic cells (all the other cells in an organism that do not contribute to gamete formation).

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Embryogenesis and Fetal Growth

The oocyte completes its first meiotic division after ovulation and its second meiotic division only if fertilized. After fertilization of the oocyte, the male and female pronuclei fuse to form a diploid nucleus. Cell division then begins and progresses to the blastocyst stage. The blastocyst implants in the lining of the uterus at 6 to 7 days after ovulation. The embryonic period begins at implantation and ends with the closure of the palatal shelves, on day 56 to 58 of gestation. During the embryonic period, most of the organs and other bodily structures begin to form. During the fetal period, which extends from the end of the embryonic period to birth, growth is characterized by continued morphological, biochemical, and physiological maturation. Significant development of several organ systems continues during the fetal period and after birth, including the central nervous system, reproductive system, and immune system.

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Reproductive and Developmental Toxicity

Reproductive toxic effects can include either parent or the offspring. Characteristics that distinguish reproductive toxicity from other toxic effects include the following: (1) adverse effects in an exposed person that may only become manifest in the fetus or offspring (eg, an exposure to a reproductive toxicant in a male may produce an effect in the conceptus); (2) infertility may not be evident until children are desired and may therefore go unnoticed for long periods; and (3) normal reproductive function is only expressed intermittently. Disturbances of the reproductive process from occupational reproductive hazards can produce a broad range of potential toxic effects. Table 1 identifies potential reproductive toxicity end points and their prevalence in the general population.

TABLE 1

TABLE 1

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Developmental Toxicology

Development can be disrupted by toxicant exposures to either parent before conception, exposures to the mother during pregnancy, and by exposures after birth via lactation or via direct exposure to the child. Toxicants that cause mutations, epigenetic changes, or other damage to germ cell DNA can, if they do not result in death of the germ cell, cause developmental toxicity. Germ cell lines and organ systems have different critical windows of development. Therefore, exposure to the same dose of a toxicant will have very different effects at different developmental stages. The axiom that “the dose makes the poison” holds true for developmental toxicology only if one also takes into account the developmental stage at which the dose was delivered. Detailed reviews of critical developmental windows for different organ systems and their relevance to developmental toxicology have been published.21 The spectrum of possible adverse developmental effects of a toxicant includes death, malformation, altered function, decreased growth, and increased risk of diseases, such as cancer, heart disease, and diabetes, later in life.

Mechanisms of reproductive and developmental toxicity include mutations, chromosomal damage, epigenetic changes such as altered DNA methylation, altered mitosis, altered nucleic acid integrity or function, diminished supplies of precursors or substrates, decreased energy supplies, altered membrane characteristics, osmolar imbalance, enzyme inhibition, and hormone receptor binding. The effects of toxicants are modulated by the genetics of the exposed man or woman and, in the case of developmental toxicity, conceptus. Recent research efforts have been redirected toward defining the mechanisms by which common genetic variants, known as genetic polymorphisms and present in 1% or more of the population, modulate the effects of toxicants. In particular, many studies have investigated the effects of polymorphisms in genes that encode for enzymes involved in the metabolism of drugs and toxicants. For example, women who have polymorphisms in genes CYP1A1 and GSTT1, which encode for metabolizing enzymes, have an increased risk of bearing a low-birth-weight child if they smoke during pregnancy compared with women who smoke, but do not have these polymorphisms.22

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Availability of Reproductive Toxicology Data

Occupational exposure to reproductive toxicants may occur via inhalation, skin absorption, or ingestion. However, there may be limited or no toxicological information available for many industrial chemicals. Furthermore, even for compounds for which there is toxicological testing data, the data often do not include assessment of the effects on male or female reproductive function or developmental effects on the offspring. In addition, extrapolating the health effects of animal toxicity studies to humans is significantly confounded by dose-response effects and by cross-species differences in sensitivity and susceptibility to mutagens and teratogens. Despite this concern, animal toxicology data may be the only data available for reproductive and developmental toxicity risk assessment and can be very useful in assessing whether a chemical poses a potential hazard to human reproduction and development. Although reproductive and developmental toxicology information may be lacking for many chemicals, mutagenic agents should be considered to be potential reproductive toxicants, since they are genotoxic and could produce adverse outcomes from direct actions on germ cells.

Currently, only a few agents or conditions have been identified as being definitely capable of producing structural abnormalities or birth defects in humans in the absence of maternal toxicity. A recent review summarizes the scientific evidence linking environmental exposures to chemicals and radiation with human adverse pregnancy outcomes.23 Several agents such as dibromochlorpropane, ionizing radiation, lead, and 2-bromopropane have been known to affect human spermatogenesis.1,24,25 Ionizing radiation and 2-bromopropane have also been recognized as destroying ovarian follicles.24,25 A much broader range of agents are recognized as having an effect upon or the potential to produce reproductive or developmental toxicity based on animal toxicology studies.

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Framework for the Assessment of Reproductive and Developmental Health Risks

The assessment of occupational reproductive and developmental risks, like any risk from an occupational hazard, involves several distinct steps including hazard identification, dose response assessment, exposure assessment, and risk characterization. For reproductive hazards, there may be limited information concerning the effects of some chemical agents and there can be considerable uncertainties in determining reliable risk estimates. The process of risk assessment may require a multidisciplinary team of occupational health professionals from several disciplines including occupational medical specialists, toxicologists, obstetrician/gynecologists, and exposure assessment specialists, such as industrial hygienists, and other health professionals.

Some workplaces have comprehensive occupational medicine and industrial hygiene resources and can assess workplace exposures and hazards throughout the worksite. In workplaces with appropriate engineering controls, existing industrial hygiene data may be able to confirm that all chemicals are well controlled, such that air concentrations are quite low or nondetectable and skin exposures are precluded by controls, work practices, or use of appropriate personal protective equipment (PPE). Review of the chemicals in use should be able to identify a subset of agents that might pose reproductive or developmental hazards at some dose (recognizing the limitations in the toxicology database). Regular review of new scientific study information from reproductive/developmental toxicity studies permits timely updates of risk characterizations. In the optimal situation there will be both comprehensive exposure data, such as personal environmental exposure monitoring or biomonitoring, and high-quality, robust reproductive and developmental toxicity data from human epidemiological studies and/or from animal toxicological studies. In such situations, risk assessment principles can be used to apply uncertainty factors to No Observed Adverse Effect Levels or Lowest Observed Adverse Effects Levels from animal toxicology studies or to levels at which effects were observed in human epidemiological studies to derive risk-based exposure levels.26 However, if there are exposures to multiple reproductive toxicants, the combined effects must also be considered.

The following three examples are intended to illustrate the application of these principles to evaluation of individual workers.

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Case 1: Preconception—A Male or Female Employee Indicates Intention to Conceive

A 29-year-old operating room nurse is referred because she and her husband would like to try to conceive, but she is concerned about possible effects of her work exposures during pregnancy. Her spouse is employed as a plant operator in the sunscreen industry.

This is in many ways the ideal scenario because the employee is seeking advice before she becomes pregnant. This scenario provides the opportunity to optimize health and work and home environments before conception. However, insufficient data on some chemicals' or agents' reproductive health effects, legal issues, and confounding factors may make this task more difficult. Approximately 35% of all pregnancies in the United States are unintended so the female employee may not seek advice about possible exposures prior to her pregnancy.9

A thorough medical and occupational and environmental history is essential. In addition to routine past medical and surgical history, family history, and prescription and over-the-counter medication and supplement history, a thorough gynecological and obstetric history should be obtained from the employee and a reproductive history should be obtained for her husband. A detailed exposure history of chemical, physical, and biological agents to which the employee is potentially exposed at work and in the home is critical. In this case of an operating room nurse, anesthetic gases, ionizing radiation exposure, infectious agents, prolonged standing, and shift work are among the occupational exposures to be considered. In addition, the work exposures of her spouse should be identified. These would include active and inert ingredients. Material safety data sheets can be obtained from employers to assist in identifying the components of various products used in the workplace. Nonoccupational exposures to be considered for both spouses include smoking, infectious agents, use of alcohol, exercise, hobbies, personal care products, and cleaning agents.

A hazard evaluation of the agents to which the employee and her husband are exposed at work as well as at home, then needs to be completed to identify which agents may pose reproductive or developmental hazards. However, material safety data sheets rarely provide detailed information about reproductive and developmental toxicity. For resources that may be useful in identifying reproductive and developmental hazards see the Appendix.

Next, the extent of the employee's and her husband's exposures to the agents identified as reproductive or developmental hazards must be assessed (exposure assessment). Estimates of frequency of exposure, duration of exposure, and route(s) of exposure, and concentration or intensity should be obtained for each agent that may cause reproductive effects. It is also important to ascertain whether any exposure control measures, such as engineering controls or personal protective equipment, are used in the workplace or at home. If the employer has conducted personal exposure monitoring for the employee or her husband (eg, radiation dosimetry) or ambient exposure measurements in the workplace, the results should be obtained and reviewed. A worksite evaluation by an industrial hygienist may be very useful. For selected agents, such as lead or mercury, biological monitoring may aid in quantifying exposure.

Risk characterization considers all the gathered data on toxicity and exposure to determine whether the employee's and/or her husband's estimated levels of exposure to the agents that have been identified as potential reproductive and developmental hazards pose a risk. Their estimated exposure levels should be compared with levels that have been demonstrated or strongly suspected to cause adverse reproductive effects in epidemiological studies or animal studies. In the classical risk assessment paradigm, if either the employee or her husband is exposed to an agent above or near levels associated with adverse effects, then there is considered to be significant risk. However, in the real world there may be incomplete data both on the hazard identification side and on the exposure side, and recommendations must be made on the basis of the available information.

Risk communication is the next critical step in which the employee and her husband are provided with the information they need to make informed decisions about the reproductive health risks of their exposures. It is important to answer all questions fully and to provide the best available information, including a discussion of the limitations of that information.

Risk management is the final step in the evaluation. It requires that the physician, patient, her husband, and their employers work together to decrease or eliminate any potential workplace (or nonworkplace) reproductive risks that were identified. Exposure reduction or elimination is the most desirable approach to risk management. Options include eliminating the chemical(s) or agent(s) or replacing it with a safer one, implementing or improving engineering controls, designing and enforcing safer work practices, and issuing or upgrading personal protective equipment. If none of these can achieve a safe environment, restrictions or a temporary transfer may be required. If the employer cannot or will not reduce exposure and no unexposed job locations for a temporary transfer are available, then the employee and her husband may face the difficult decision of quitting their jobs or continuing to work in situations that pose potential reproductive risks. Temporary disability benefits may not be available for a woman or spouse attempting to avoid exposure to prevent a possible adverse reproductive outcome. Temporary disability benefits are more likely to cover a pregnant woman in situations deemed to be high-risk or with current pregnancy complications. Permanent removal from a job is the least desirable action, and it is important to help the employee and her husband evaluate all other possible options and uncertainties that might still exist with other workplace assignments.

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Case 2: Pregnancy—An Employee Indicates She Is Pregnant

A 32-year-old aircraft maintenance technician, whose duties include engine testing, refueling, and repair of airplanes and helicopters, is referred to the occupational physician after a positive pregnancy test. Her supervisor requests your recommendations regarding her fitness for duty. On the day of her clinic visit, it has been 8 weeks since her last menstrual period.

This is a much more common scenario than Case 1. It is too late to prevent exposures during the preconceptional period and during the embryonic period, when many of the major organ systems are forming. A hazard evaluation and exposure assessment similar to Case 1 of employee's occupational and home environments needs to be performed to characterize the risks of the exposures that have already occurred and those that can be changed or stopped to prevent further damage. Examples of possible hazards she may have been exposed to include jet fuel, degreasing agents, and other solvents. Exposure to organic solvents during pregnancy has been associated with increased risk of spontaneous abortion, and may also be associated with increased risk of birth defects.27,28 However, organic solvents represent a diverse group of chemicals with differing toxicological properties, and the epidemiological database is insufficient to draw conclusions about the reproductive and developmental toxicity of most individual organic solvents. An airplane technician may be exposed to high noise levels that may reach up to 120 decibels during engine testing and there is some suggestion that high noise exposures may affect the fetus although this is controversial.29 In this example, the pregnant technician can readily protect her cochlear hair cells by well-fitted ear-muffs and plugs, but this leaves the fetus unprotected, since the abdominal wall, myometrium, and amniotic sac serves only as a “low-pass filter,” allowing low-frequency sound to pass through without attenuation.

If the risk assessment indicates that significant exposures to developmental toxicants may have occurred, the development of the major organ systems can be evaluated with fetal ultrasound examination. If significant exposure to mutagens may have occurred, amniocentesis may be indicated. Termination of pregnancy is rarely indicated unless there is frank maternal poisoning or documented fetal effect. If exposure is negligible or low then reassurance is generally indicated. In the intermediate situation in which no maternal poisoning or documented fetal effects have occurred, but the risk characterization leads to the conclusion that significant developmental risks exist in the workplace or home, then prevention of continued exposure to these risks must be the priority. In all of these possible situations, it is important to fully communicate to the patient that the results of the risk characterization, including an assessment of the uncertainties and limitations in the conclusions that have been reached.

Finally, steps must be taken to reduce or eliminate the identified risks. The tiered risk management strategy outlined for Case 1 also applies here, but in this case of a pregnant employee, temporary disability leave is a viable option if the preferred alternatives of exposure reduction/elimination or temporary job transfer are not available and if one has concluded that the aircraft maintenance technician is subject to high-risk workplace exposure(s). Unlike this patient, some pregnant employees may not wish to identify themselves as such to their employers. They may feel that it is intrusive to disclose their pregnancy or fear that they will be laid off if they disclose their pregnancy. While it is illegal for an employer to terminate a worker because of pregnancy, such fears may not be groundless for some workers. In such situations, it is important for the physician to help the pregnant worker to fully understand and weigh the potential medical consequences of their decision.

About 35% of all pregnancies are unplanned.9 Pregnancy may not be recognized early enough for reassignment to protect a fetus during critical periods of development. These realities may reduce the effectiveness of a recommendation for self-reporting pregnancy. In addition, a requirement for employee notification of pregnancy, intended pregnancy or infertility status to the employer may be viewed as intrusive and some employees may feel this requires them to disclose intimate personal details. Such disclosure may include health information that would otherwise be protected under federal law. Employees may, for whatever reason, choose not to identify themselves as being at risk, making passive and universal preventive measures, as well as no-fault exposure reporting programs, all the more important.

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Case 3: Infertility

A 53-year-old firefighter and his wife, a 44-year-old hairdresser, have been trying to conceive without success. They are concerned that occupational exposures have caused their troubles. Several issues are raised by this case. Fertility declines with age in both men and women. Twenty percent of married women aged 40 to 44 are infertile.9 The chances for conception in less than 12 months in partners of men older than 40 are half those of men younger than 25 years of age.7 On the contrary, both husband and wife in this scenario are employed in occupations that involve exposures to chemicals and, in the case of the husband, physical agents, that is, heat. Exposure to heat, resulting in increased scrotal temperature, has been associated with decreased semen quality.30,31 Hairdressers have been reported to have slightly lower fecundability (probability of conception) than controls,32 and hairdressing involves exposure to numerous chemicals, some of which have been shown to cause reproductive toxicity in animal studies.33

A fertility specialist should evaluate both husband and wife to try and pinpoint where the fertility problem(s) lies. Such an evaluation may yield the cause of infertility in all but 10% to 15% of couples. It is estimated that 30% to 40% of infertility is due to male infertility issues such as sperm abnormalities; 45% to 55% is due to female infertility issues such as ovulatory problems; and 30% to 40% is due to tubal or peritoneal dysfunction.34 Decreased libido, impotence, intercourse timing, and intercourse frequency also affect fertility. Hazard evaluation, exposure assessments, and risk characterization should be done for both husband and wife as outlined for Case 1, unless the fertility evaluation clearly points to one or the other. If there is significant workplace or home exposure to an agent known to cause infertility, the couple needs to be informed of the available data and involved in decision making. The same, tiered risk management strategy outlined for Case 1, with the same caveat that temporary disability leave is not likely to be an option, applies in this case.

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Temporary Reassignment

In all of the scenarios presented, temporary reassignment should be recommended if the conclusion of the risk assessment is that there is exposure to a reproductive or developmental toxicant that cannot be adequately controlled through engineering or work practice controls alone. When personal protective equipment may be required to control exposure, temporary reassignment should be considered in most of the above scenarios if there is a significant exposure to a known reproductive hazard because PPE may not offer perfect protection and because there are limited data on respirator use during pregnancy.35 Temporary reassignment should also be considered when an individual's medical history or risk factors suggest a need.

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Legal Considerations

Two sources of antidiscrimination protections afforded the pregnant employee are Title VII of the Civil Rights Act of 1964 as well as the related Pregnancy Discrimination Act Amendment of 1978. These federal acts protect against discrimination due to pregnancy, childbirth, or related medical conditions, and apply to state and local governments as well as employment agencies, and labor organizations. The amendment states, “Women who are pregnant or affected by related conditions must be treated in the same manner as other applicants or employees with similar abilities or limitations.”36 Thus, the employer should treat a pregnant employee unable to perform her job the same as other temporarily disabled employees. “For example, if the employer allows temporarily disabled employees to (perform) modify tasks, perform alternative assignments or take disability leave or leave without pay, the employer also must allow an employee who is temporarily disabled due to pregnancy to do the same.”36 These acts also state that pregnant employees who are able to perform their job should be allowed to continue working, even if they were absent for a condition and have now recovered. These particular laws do not predetermine the length of time an employee must take off during pregnancy or after childbirth. If a pregnant woman does take time off, the job should be held for her as it would be for others on sick or disability leave, and any continuance or accrual of benefits that would occur during other types of disabilities should also relate to pregnancy-related conditions. “Employees with pregnancy-related disabilities should be treated the same as other temporarily disabled employees for accrual and crediting of seniority, vacation calculation, pay increases, and temporary disability benefits.”36 Of course, the employer can also require the employee to submit information from their physician regarding their “inability to work” or need for reassignment before granting any pay, benefits, or reassignment.37

Other bodies of law aimed at the protection of the pregnant employee from discrimination are the Equal Employment Opportunity Act, the Americans with Disabilities Act, and the Family and Medical Leave Act. For instance, employees who feel their rights have been violated may file a formal grievance with the US Equal Employment Opportunity Commission, as outlined in the Equal Employment Opportunity Act, and related legislation—“It is also unlawful to retaliate against an individual for opposing employment practices that discriminate based on pregnancy or for filing a discrimination charge, testifying, or participating in any way in an investigation, proceeding, or litigation under Title VII.”36 The Family and Medical Leave Act covers private sector employers with at least 50 employees within a 75-mile radius. Employees must have worked for the employer for at least 12 months or 1250 hours. Covered employers are required to provide up to 12 weeks of unpaid medical leave (job protected) during a 12-month period to eligible employees for childbirth and newborn care, adoption or foster care placement, care for immediate family members with a serious health condition, or to handle a serious personal health condition including maternity related medical conditions.

“Disability” is usually narrowly defined by insurance carriers and may not cover situations where employees are removed from work to prevent potential harm from occupational exposures. Even when disability leave is granted, compensation may be inadequate to assure economic security, especially for an already low-paid worker.38 (As noted, certain individuals may not qualify for Family and Medical Leave Act, for example, they work for a small company, have not met the time requirements of the job, have other federal agency protection, etc).

As with any US worker, the pregnant employee is afforded some measure of protection under other federal laws governing the responsibilities of employers to provide safe workplaces.39,40 The OSH Act creates an affirmative duty for employers to assure a baseline level of workplace safety for their employees. The employer must provide workers with protection against personal injury and illness resulting from hazardous working conditions. The General Duty Clause of the OSH Act states that the employer should provide “a place of employment...free from recognized hazards that were causing or likely to cause death or serious physical harm...assure so far as possible...safe and healthful working conditions.”39 Thus, while the OSH Act does not include a specific pregnancy standard, the General Duty Clause could reasonably be applied to known exposure/workplace hazards to pregnancy. This approach has been adopted in the past by OSHA in other areas.

It should be noted that the discussion herein presents nonexhaustive examples of a few federal antidiscrimination protections afforded pregnant women in the workplace. There are other federal protections, and perhaps more importantly, every (or nearly every) state jurisdiction in the United States also has state-specific protections that provide additional or more stringent protections. The employer is invariably held to both (federal and state) sets of protections, and in those instances where there is a conflict between federal and state law, the employer is generally held to the higher or more stringent of the two standards. Thus, the practitioner should, at a minimum, be aware that these other protections exist, and should seek legal counsel (to include both federal and state-specific guidance) whenever there is a potential for a pregnant employee to suffer an adverse employment action due to the fact that she is pregnant.

Currently there are few, if any general protections or rights of monetary recovery under US federal law that apply to women who are planning to become pregnant or to individuals who believe their infertility or pregnancy losses are due to workplace exposures. However, the civil tort systems in every state jurisdiction would typically provide such allegedly aggrieved parties a forum to pursue damages through civil litigation. Under certain circumstances (eg, where the employer's commercial activities and employee exposure result from interstate or multistate commerce, or are isolated to the District of Columbia) such claims may be brought under federal jurisdiction.

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Individual Versus Population-Based Interventions

Whereas temporary reassignment is an action taken at the level of the individual worker, the following sections discuss population-based programs to reduce the potential effects of reproductive hazards in the workplace. Primary prevention of adverse reproductive health effects includes worker education to reduce lifestyle risk factors (smoking cessation, avoiding alcohol and drug abuse, avoidance of behaviors that increase the risk of sexually transmitted diseases, improved nutrition, and exercise). In addition, workers should receive hazard communication regarding the presence of potential reproductive toxicants in the workplace, as well as education regarding appropriate measures to reduce exposure to these hazards (engineering controls, administrative controls, and personal protective equipment). Workers should also be advised to avoid significant reproductive hazardous exposures in their home or other activities. All workers (male and female) should be encouraged to present to the occupational health provider or their treating physician for preconception counseling and to inform occupational health when pregnancy is confirmed.

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Medical Surveillance

Medical surveillance should be considered for populations at risk of exposure to a significant reproductive hazard, particularly if there is laboratory monitoring available (such as blood lead) that predict risk of adverse reproductive outcomes. The current OSHA lead standard 1910.1025 for general industry and 1926.26 for the construction industry recommends removal from work if a pregnant women's lead level is 30 μg/dL or higher. However, this standard should be revised given new available data. Multiple studies have shown fetal effects including cognitive delays down to a fetal blood lead of 10 μg/dL and some effect down to 5 μg/dL. It seems more reasonable to keep a pregnant woman or worker planning on becoming pregnant blood lead to 10 μg/dL or less. The components of any medical surveillance program should be based upon the type of hazard, the availability of appropriate tests to evaluate the risks or adverse effects of the specific hazard, and the benefits of early detection. Reproductive history questionnaires can be administered to a population at risk for the purpose of determining whether there are any unusual patterns or clusters of reproductive health problems. Ideally, information from a control nonexposed population should be collected to serve as a comparison group. End points that can be considered include live births, fetal loss, and birth defects. If potential problems are identified that could be related to occupational exposure, a reassessment of exposure potential and reproductive toxicity data may be required for a work site or a specific industrial process.

Medical screening to assess the physiological status of the employee's reproductive system may also be indicated for assessment of unusual reproductive health problems if there is an available and appropriate test. Questionnaires also provide a database that could facilitate a retrospective assessment of the effects of a work place on reproductive function. Consultation with an epidemiologist or biostatistician may help to interpret the significance of population data from reproductive health questionnaires.

Although several laboratory tests are available to assess reproductive function, their use in routine medical surveillance has not been established.41 In general, assessment of male fertility is simpler, since spermatozoa can be readily obtained by semen analysis, as opposed to the more difficult procedure of harvesting ova. Sperm parameters that can be monitored include concentration and morphology but any conclusions regarding the significance of a finding must consider variables that can affect one or more semen parameters such as duration of abstinence prior to sample collection, use of recreational drugs or therapeutic medications, age, smoking, diet, radiation exposures, elevated scrotal temperature, and testicular trauma.42 Monitoring of urinary reproductive hormone concentrations in daily samples for one or multiple menstrual cycles has been used to assess female reproductive function,43,44 but these methods are time-consuming for the woman and are probably not practical for surveillance. Several serum biomarkers of ovarian reserve have been proposed that could potentially be used in surveillance45,46; however, other variables that can affect the results, such as age, smoking, or treatment with antineoplastic agents or radiation must be considered. Future research may identify additional biomarkers for use in medical surveillance of exposed workers. These may include genetic polymorphisms and sister chromatid exchange.

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Notification of Pregnancy

The purpose of employee notification is to provide an opportunity for counseling the employee during pregnancy when issues concerning potential reproductive risk are most relevant. The employer may request that the employee's personal physician comment on her ability to continue performing tasks associated with her job. This option is not an adequate substitute for aggressive risk assessment and communication. In addition, notification of pregnancy may not be received until after the pregnancy is recognized and after the critical period of embryonic development. Employee notification of intended pregnancy, that is seemingly more intrusive, could offer the advantage of earlier intervention. Even if notification is encouraged, some employees may choose not to identify themselves as pregnant or as planning a pregnancy. Therefore, employers must be proactive in identifying and controlling potential workplace reproductive and developmental hazards.

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Breast Feeding Policy

Physicians who see nursing mothers that work in environments where they are exposed to substances that could be excreted in breast milk such as selected organic solvents, metals, and pesticides, should assess whether exposure would be sufficient to produce significant concentrations in the breast milk of employees who are breastfeeding. Human breast milk has been determined to contain a broad range of chemical contaminants.47,48 In general, the benefits to the infant of breastfeeding are thought to outweigh the risks of exposure to chemicals via the breast milk for most women.49,50 Chemicals found in human milk are generally fat soluble and poorly metabolized. Therefore they persist in body fat. In some instances, mothers with occupational exposures to certain chemicals can have concentrations of chemical contaminants that considerably exceed the levels that are permitted by the Food and Drug Administration in cow's milk.4 Employees should be notified of the potential for accumulation of chemical contaminants in breast milk. Assignment of women who are breast feeding to positions where there are exposures that would result in an infant receiving a chemical intake in excess of the acceptable daily intake for that agent should be closely assessed.

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Para-occupational Exposures

Physicians should also consider that the worker may bring work contaminants into the home environment, which could affect development of offspring.51 A number of approaches may be used to reduce or avoid contamination of the home environment and thereby protect a developing fetus or developing infant and child. These include improved housekeeping in the workplace, employer laundry of work clothes and protective garments, the construction and use of “clean” and “dirty” change rooms, and mandatory use of showers at the end of the workday.

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Reproductive Health Hazard Management Options

Several options should be considered in managing reproductive risks, performing risk assessments, and dealing with potential uncertainties. The decision to implement specific options at a specific workplace should be based upon an assessment of potential risks and upon the characteristics of the population at risk. Before implementing reproductive health hazard management measures in a company, legal review may be considered to ensure compliance with all federal, state, and other regulations pertaining to discrimination and protection of employees' rights and disabilities.

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ACKNOWLEDGMENTS

The document was reviewed by the ACOEM Council of Scientific Advisors, and approved by the ACOEM Board of Directors on March 25, 2011. The Task Force would also like to acknowledge Joseph Fedoruk, MD, who as the leading author of the 1994 ACOEM statement on Reproductive Hazards, provided peer review and insightful input in this document. The Task Force would also like to thank James Tacci, MD, MPH, JD, for providing legal review.

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        Appendix Resources for Information About Reproductive Hazards

        Computer Databases/Web-based Resources

        National Institute for Occupational Safety and Health (NIOSH). The Effects of Workplace Hazards on Female Reproductive Health—www.cdc.gov/niosh/docs/99-104

        Occupational Safety and Health Administration (OSHA). Safety and Health Topics: Reproductive Hazards—www.osha.gov/SLTC/reproductivehazards/index.html

        OTIS: Organization of Teratology Information Specialists—http://www.otispregnancy.org

        National Birth Defects Prevention Network—www.nbdpn.org

        TERIS: Teratogen Information System, Seattle–-http://depts.washington.edu/∼terisweb/teris/

        Developmental and Reproductive Toxicology Database (DART), National Library of Medicine–-http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?DARTETIC.htm

        The Center for the Evaluation of Risks to Human Reproduction–-http://cerhr.niehs.nih.gov/

        Reproductive Toxicology Center (REPROTOX)—www.reprotox.org (telephone: 202/293-5946)

        Government Agencies

        1. Environmental Protection Agency, Washington, DC Regional Offices
        2. National Institute for Occupational Safety and Health
        3. Occupational Safety and Health Administration
        4. Agency for Toxic Substances and Disease Registry

        Phone Numbers

        The North American Teratology Information Service, Toronto (telephone: 416/813 6978)

        US Regional Poison Centers (telephone: 800/222-1222)

        Textbooks

        Frazier LM, Hage ML. Reproductive Hazards of the Workplace. New York, NY: John Wiley & Sons; 1998

        Jennison EA. Reproductive hazards in the workplace. In: Alaimo RJ, ed. Handbook of Chemical Health and Safety. Washington, DC: Oxford University Press; 2001.

        Copyright © 2011 by the American College of Occupational and Environmental Medicine