12.14 Reproductive and Developmental Toxicants

Reproductive toxicants are chemical, biohazardous, or physical agents that can impair the reproductive capabilities in men and/or women. Developmental toxicants interfere with proper growth or health of the child acting at any point from conception to puberty.

12.14.1       Adverse Effects Caused by Reproductive and Developmental Toxicants

1. Genetic defects: Changes in germ cells that can be passed from one generation to the next, as well as genetic problems that arise at the point of fertilization (such as Down Syndrome). It is estimated that 20% of human malformations are due to inherited genetic defects that are present in the egg or sperm cell.

2. Infertility: The inability of a couple to conceive after one year of regular intercourse without the use of contraceptives. One in twelve couples in the U.S. is infertile according to the Agency for Toxic Substances and Disease Registry (ATSDR). Hazardous exposures can cause infertility in males by interfering with hormones, damaging the testes (thus affecting sperm production), or by damaging the sperm leading to a reduction in sperm count, viability, motility, or functional capabilities. In women, the lack of ovulation or abnormal menstruation may cause infertility. This may be due to damage to the fallopian tubes, direct damage to the egg, or a change in the balance of sex hormones.

3. Menstrual disorders: This effect has not been studied thoroughly; however, any chemical that influences the balance of sex hormones could potentially cause menstrual irregularities.

4. Impotence or decreased libido: Chemicals that affect the nervous system or the secretion of sex hormones have been shown to lower libido or alter sexual response in both males and females.

5. Spontaneous abortion: Spontaneous abortion or miscarriage is the loss of the embryo or fetus before full term. Approximately 40% or more of all pregnancies end in spontaneous abortion (ATSDR). Spontaneous abortion may be caused when toxicants: a. Cause damage to the genetic material in the egg so that the embryo cannot survive; b. Prevent the fertilized egg from implanting itself in the uterus; or c. Directly affect the developing embryo or fetus, causing a lethal toxic effect.

6. Stillbirth: Birth of a dead fetus. The death occurs late in the pregnancy or during birth.

7. Birth defect: Physical abnormality or malformation present at birth, although it may not be detected. Two to three percent of all newborns have a serious birth defect (ATSDR). Approximately two-thirds of human birth defects have no known cause. The proportion that may be associated with exposure to hazardous substances is unknown. Teratogens are agents that cause birth defects to the embryo or fetus and usually occur during the first trimester.

8. Low birth weight and premature birth: Agents can delay the growth or harm the health of the embryo or fetus without causing physical defects or death. Low birth weight is directly related to an increased risk of illness or death in the first year of life. Premature births are at risk for low birth weights and may suffer from the effects of immature organ systems.

9. Childhood cancer: Carcinogens can affect the fetus by passing through the placenta to the fetus. These transplacetal carcinogens can later cause cancer in the child or young adult. Research in this area is limited; however, work environments with exposures to metals, solvents, paints, and agricultural chemicals are of concern.

10. Developmental disorders: Behavioral effects include hyperactivity, decreased attention span, slow learning ability, and in severe cases, mental retardation. These may be temporary or permanent effects. Due to limited studies, very few industrial chemicals that cause neurobehavioral defects have been identified.

11. Breast milk and other exposures after birth: Some chemicals are stored in fat tissues and, since breast milk is rich in fat, infants can be exposed to these toxic chemicals. However, breastfeeding has many positive benefits that may outweigh the infant’s risk of chemical exposure. Your healthcare provider should be consulted in these cases.

12. Skin or clothing: Skin or clothing contaminated with chemicals can also be a route of exposure for infants and children at home. Using good work practices and leaving contaminated clothing at work will prevent this type of exposure.

12.14.2       Hazards of Reproductive and Developmental Toxicants

The greatest susceptibility to reproductive toxicants in women is usually during the first three to twelve weeks of pregnancy. During this period, a woman may not know that she is pregnant.

In order to appropriately recognize and control chemicals that may cause an increased risk of harm, three categories have been established. Toxicants that fall into Category 1 must be labeled Danger–Reproductive and Developmental Toxicant. The lab safety coordinator (ultimately the principal investigator) is responsible for reviewing all lab chemicals and must determine whether any Category 1 chemicals are present. The lab safety coordinator also identifies any new Category 1 chemicals at the time of purchase. Pesticides have not been included in the tables.

12.14.3       Handling Procedures for Reproductive and Developmental Toxicants

Volatile reproductive toxicants must be handled inside a chemical fume hood to prevent inhalation exposure. Standard PPE (gloves, lab coat, and safety glasses) is recommended for handling Category 2 and 3 reproductive toxicants. It is recommended that Section 12.11.8, Handling Procedure for Select Carcinogens, be followed when using Category 1 reproductive toxicants.

12.14.4       Storage of Reproductive and Developmental Toxicants

See Section 9, Proper Chemical Storage, for specific storage information. Reproductive toxicants should be labeled as such within the respective storage group.

12.14.5       Disposal of Reproductive and Developmental Toxicants

Refer to Chapter VI, Hazardous Waste Directory, for specific disposal information. Most reproductive toxicants will need to be labeled for collection by EH&S.

12.14.6       Emergency Response: Exposure

1. Skin: Immediately remove affected clothing and flush contacted tissue with copious amounts of water for 15 minutes. If the skin is injured, proceed to the nearest hospital ER.

2. Eye Contact: Rinse eyes with copious amounts of water for 15 minutes. Hold lids open while rinsing. Seek medical evaluation.

Complete an Accident-Illness Report Form as soon as possible and mail to EH&S at J3-200.

12.14.7       Emergency Response: Spills

Small spills can be cleaned with a universal absorbent while wearing safety goggles, gloves and a lab coat.

For large spills (>200 ml), evacuate the lab and call EH&S for clean-up.

12.14.8       Category 1 Reproductive and Developmental Toxicants: Sufficient Human Evidence

Category 1 agents are known human reproductive and/or developmental hazards. The scientific evidence to support this consists of sufficient epidemiologic evidence or human case studies along with strong supporting animal evidence for at least one adverse reproductive effect. Because the human data necessary to support this category are generally limited, there are currently few agents classified in this category. The potential reproductive effects listed are based on observation of toxic effects in studies of exposed humans or animals. Biohazardous and physical hazards are also included in this section.

Table 12.14.8.1 Category 1

Chemical

Reported Adverse Effects

Aniline

Female infertility, spontaneous abortion, growth retardation, developmental disorders

Bulsulfan

Male and female infertility, spontaneous abortion, birth defects, and growth retardation

Cancer chemotherapeutic drugs (e.g., methotrexate, cyclophosphamide)

Male and female infertility, spontaneous abortion, birth defects, growth retardation, some contaminate breast milk

Carbon disulfide

Reduced male sex drive, male and female infertility, spontaneous abortion, growth retardation, menstrual disorders, breast milk contamination

Carbon monoxide

Female infertility, spontaneous abortion, growth retardation, functional deficit

Chlorambucil

Male and female infertility, birth defects, developmental disorders

Dibromochloropropane (DBCP)

Male infertility, genetic defects, altered sex ratios

Diethylstilbestrol (DES)

Male infertility, functional deficit, childhood cancer

Dinitrotoluene (DNT)

Spontaneous abortion, male infertility, growth retardation, developmental disorders

Ethyl alcohol

Male infertility, developmental disorders, birth defects, low birth weight or premature births

Lead

Male and female infertility, spontaneous abortion, growth retardation, functional deficit, breast milk contamination

Mercury (organic such as methyl mercury)

Male infertility, birth defects, growth retardation, functional deficit, breast milk contamination

Methylene chloride

Low birth weight, spontaneous abortion, developmental disorders, breast milk contamination

Chemical

Reported Adverse Effects (continued)

Phenol (carbolic acid)

Altered sex ratio, spontaneous abortions, impotence

Polychlorinated biphenyls (PCBs)

Male and female infertility, spontaneous abortion, growth retardation, breast milk contamination

Warfarin

Birth defects, developmental disorders, spontaneous abortions

Toluene (methyl benzene)

Low birth weight, developmental disorders, birth defects, menstrual disorders, male and female infertility


Biohazardous Material           

Reported Adverse Effects

Cytomegalovirus

Spontaneous abortion, birth defects, growth retardation, developmental disorders, breast milk contamination

Hepatitis B virus

Growth retardation, liver disease in infected offspring, breast milk contamination

HIV

Functional deficit, childhood cancer

Parvovirus B19, Human

Adverse pregnancy outcomes

Rubella virus (German measles)

Birth defects, growth retardation, developmental disorders

Toxoplasmosis

Spontaneous abortion, birth defects, developmental disorders

Varicella-zoster virus (chicken pox and shingles)

Birth defects, growth retardation


Physical Hazard

Reported Adverse Effects

Excessive heat

Male infertility

Heavy physical exertion (e.g., repetitive heavy lifting, stooping and/or climbing)

Spontaneous abortion, growth retardation

Ionizing radiation

Male and female infertility, spontaneous abortion, birth defects, growth retardation, developmental disorders, childhood cancer


12.14.9       Category 2 Reproductive and Developmental Toxicants: Sufficient Animal Evidence/Limited Human Evidence

The agents listed in this category are probable or possible human reproductive hazards. The scientific evidence to support this includes data from experimental animal studies and/or limited human data. The minimum evidence necessary is a single, well-conducted study in one experimental animal species for one adverse reproductive effect. The potential reproductive effects listed are based on observation of toxic effects in studies of exposed animals and humans.

Table 12.14.9.1 Category 2

Chemical

Reported Adverse Effects

Acetaldehyde (with alcohol consumption)

Growth retardation, developmental disorders

Acetone

Female infertility, birth defects, menstrual disorders

Acrylonitrile

Male infertility, birth defects, reduced male sex drive

Aluminum

Birth defects

Ammonia

Premature birth

Anesthetic agents (e.g., nitrous oxide, halothane)

Male infertility, spontaneous abortion, birth defects, growth retardation, breast milk contamination

Antimony

Spontaneous abortion, breast milk contamination

Antimony potassium tartrate

Premature birth, miscarriages, female infertility

Arsenic

Birth defects, spontaneous abortion

Benzene

Female infertility, spontaneous abortion, birth defects, growth retardation, menstrual disorders

Boric acid, borates

Reduced male sex drive, male infertility, female infertility

Bromine

Male infertility, decreased libido, impotence, breast milk contamination

1,3 Butadiene

Male and female infertility, birth defects, growth retardation

Cadmium

Male and female infertility, birth defects, growth retardation, developmental disorders, breast milk contamination

Carbamide (urea)

Spontaneous abortion

Carbaryl

Male and female infertility, genetic defects

Carbon tetrachloride

Male and female infertility

Chemical

Reported Adverse Effects (continued)

Chloroform

Spontaneous abortion, birth defects

Copper

Spontaneous abortion, birth defects

Dimethoate

Birth defects, spontaneous abortion, male infertility

Dimethylformamide, N, N (DMF)

Spontaneous abortion, stillbirths, birth defects, female infertility

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin)

Male and female infertility, spontaneous abortion, birth defects, breast milk contamination

Epichlorohydrin

Male infertility

Ethylene dibromide (EDB)

Male infertility, birth defects

Ethylene glycol monoethyl ether (EGEE)

Birth defects, female and male infertility, menstrual disorders

Ethylene glycol monomethyl ether (EGME)

Male infertility, birth defects, developmental disorders

Ethylene oxide

Male and female infertility, spontaneous abortion, birth defects, growth retardation

Ethylene thiourea

Birth defects

Formaldehyde

Female infertility, spontaneous abortion

Gasoline

Female infertility, birth defects, menstrual disorders

Glycidyl ethers (e.g., allyl glycidyl ether, phenyl glycidyl ether)

Male infertility

Lithium

Birth defects and male infertility among patients taking lithium

Manganese

Reduced male sex drive, male infertility, breast milk contamination

Mercury (inorganic salts and metallic Hg)

Reduced male sex drive, male and female infertility, spontaneous abortion, birth defects, growth retardation, breast milk contamination

Nitrous Oxide

Male and female infertility, spontaneous abortion, developmental defects

Chemical

Reported Adverse Effects (continued)

Oral contraceptives

Reduced male sex drive, female infertility, birth defects

Paints

Spontaneous abortion, developmental disorders

Polyvinyl chloride (PVC resin)

Female infertility, spontaneous abortion, stillbirths

Selenium

Spontaneous abortion, birth defects, female infertility, menstrual disorders, breast milk contamination

Solvents

Birth defects, developmental disorders, spontaneous abortion, impotence, female infertility, menstrual disorders, breast milk contamination

Sulfur dioxide

Spontaneous abortions, female infertility, low fetal weights, birth defects

Styrene (vinyl benzene)

Male and female infertility, spontaneous abortion, breast milk contamination

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)

Spontaneous abortion, birth defects, male infertility, menstrual disorders, breast milk contamination

Tetrachloroethylene (perchloroethylene)

Female infertility, spontaneous abortion, developmental disorders, birth defects, menstrual disorders, breast milk contamination

Trichloroethylene

Male and female infertility, spontaneous abortion, birth defects

Trinitrotoluene

Male infertility

Vinyl chloride monomer

Reduced male sex drive, spontaneous abortion, birth defects, childhood cancer

Xylene

Female infertility, birth defects, menstrual disorders, breast milk contamination


Physical Hazard

Reported Adverse Effects

Low atmospheric pressure (hypobaric)

Male infertility, growth retardation

High atmospheric pressure (hyperbaric)

Male infertility, birth defects


12.14.10      Category 3 Reproductive and Developmental Toxicants: Suspect/Insufficient Evidence

The agents in this category are possible or uncertain reproductive hazards. They are suspected to affect reproductive health but the data are insufficient. The existing data are from animal studies with no human data available.

Table 12.14.10.1 Category 3

Chemical

Reported Adverse Effects

Acrylamide

Male and female infertility, birth defects, developmental disorders

Carbon dioxide

Birth defects, male infertility

Carbon tetrachloride

Male and female infertility, developmental disorders, birth defects

Chromium

Birth defects, infertility

Di (2-ethylhexyl) phthalate (DEHP)

Birth defects, male infertility, developmental disorders

Dimethyl phthalate

Birth defects, developmental disorders

Dimethyl sulfoxide (DMSO)

Developmental disorders

Epichlorohydrin

Male infertility

Ethylene thiourea

Birth defects

Halothane

Developmental disorders, birth defects

Methyl alcohol

Developmental disorders

Methyl ethyl ketone (MEK)

Developmental disorders

Methylformamide, N

Birth defects

Methylpyrrolidone

Birth defects

Nickel

Birth defects

Polybrominated biphenyls (PBBs)

Birth defects, developmental disorders

Ribavirin (virazole)

Birth defects, spontaneous abortion

Toxaphene (Camphechlor)

Developmental disorders, infertility, breast milk contamination

1,1,1-Trichloroethane

Low fetal weight, birth defects, developmental disorders


Physical Hazard

Reported Adverse Effects

Noise

Female infertility, spontaneous abortion, birth defects, growth retardation, developmental disorders

Radiofrequency and microwave radiation (non-ionizing)*

Male and female infertility, birth defects

Video display terminals (VDT)**

Spontaneous abortion, birth defects

* While there is little doubt that radio frequency and microwave radiation of sufficient intensity can damage the testes due to thermal action (tissue heating), there is little agreement as to the non-thermal effects related to these types of radiation.

** VDTs emit low-frequency electromagnetic radiation. Public concerns about the effects of VDT use and pregnancy are based on reported clusters of spontaneous abortion and birth defects among operators. The combined data of epidemiologic studies do not provide much evidence that the low frequency fields produced by VDTs are associated with adverse pregnancy outcomes.

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