Environmental toxicants and fetal development
Environmental toxicants and fetal development is the impact of different toxic substances from the environment on the development of the fetus. This article deals with potential adverse effects of environmental toxicants on the prenatal development of both the embryo or fetus, as well as pregnancy complications. The human embryo or fetus is relatively susceptible to impact from adverse conditions within the mother's environment. Substandard fetal conditions often cause various degrees of developmental delays, both physical and mental, for the growing baby. Although some variables do occur as a result of genetic conditions pertaining to the father, a great many are directly brought about from environmental toxins that the mother is exposed to.
Various toxins pose a significant hazard to fetuses during development. A 2011 study found that virtually all US pregnant women carry multiple chemicals, including some banned since the 1970s, in their bodies. Researchers detected polychlorinated biphenyls, organochlorine pesticides, perfluorinated compounds, phenols, polybrominated diphenyl ethers, phthalates, polycyclic aromatic hydrocarbons, perchlorate PBDEs, compounds used as flame retardants, and dichlorodiphenyltrichloroethane (DDT), a pesticide banned in the United States in 1972, in the bodies of 99 to 100 percent of the pregnant women they tested. Bisphenol A (BPA) was identified in 96 percent of the women surveyed. Several of the chemicals were at the same concentrations that have been associated with negative effects in children from other studies and it is thought that exposure to multiple chemicals can have a greater impact than exposure to only one substance.
- 1 Effects
- 2 Toxicants and their effects
- 3 Avoiding relevant environmental toxins in pregnancy
- 4 Natural gas development
- 5 Role of the placenta
- 6 See also
- 7 References
- 8 Further reading
Environmental toxicants can be described separately by what effects they have, such as structural abnormalities, altered growth, functional deficiencies, congenital neoplasia, or even death for the fetus.
One in ten US babies is born preterm and about 5% have low birth weight. Preterm birth, defined as birth at less than 37 weeks of gestation, is a major basis of infant mortality throughout childhood. Exposures to environmental toxins such as lead, tobacco smoke, and DDT have been linked with an increased risk for spontaneous abortion, low birth weight, or preterm birth.
Structural congenital abnormality
Toxic substances that are capable of causing structural congenital abnormalities can be termed teratogens. They are agents extrinsic to embryo or fetus which exert deleterious effects leading to increased risk of malformation, carcinogenesis, mutagenesis, altered function, deficient growth or pregnancy wastage. Teratogens are classified in four main categories:
- Drugs and chemicals. In addition to environmental chemicals, this category also includes recreational and pharamaceutical drugs in pregnancy.
- Vertically transmitted infections
- Radiation, such as X-rays
- Mechanical forces, such as oligohydramnios
Teratogens affect the fetus by various mechanism including:
- Interfering with cell proliferation rate, such as viral infection and ionization
- Altered biosynthetic pathways, as seen in chromosomal defects
- Abnormal cellular or tissue interactions, as seen in diabetes
- Extrinsic factors
- Threshold interaction of genes with environmental teratogens
Many cases of autism are related to particular geographic locations, implying that something in the environment is complementing an at-risk genotype to cause autism in vulnerable individuals. These findings regarding autism are controversial, however, with many researchers believing that increasing rates in certain areas are a consequence of more accurate screening and diagnostic methods, and are not due to any sort of environmental factor.
Toxicants and their effects
Substances which have been found to be particularly harmful are lead (which is stored in the mother's bones), cigarette smoke, alcohol, mercury (a neurological toxicant consumed through fish), carbon dioxide, and ionizing radiation.
Fetal exposure to prenatal tobacco smoke may experience a wide range of behavioral, neurological, and physical difficulties. Adverse effects include stillbirth, placental disruption, prematurity, lower mean birth weight, physical birth defects (cleft palate etc.), decrements in lung function, increased risk of infant mortality.
Elemental mercury and methylmercury are two forms of mercury that may pose risks of mercury poisoning in pregnancy. Methylmercury, a worldwide contaminant of seafood and freshwater fish, is known to produce adverse nervous system effects, especially during brain development. Eating fish is the main source of mercury exposure in humans and some fish may contain enough mercury to harm the developing nervous system of an embryo or fetus, sometimes leading to learning disabilities. Mercury is present in many types of fish, but it is mostly found in certain large fish. One well-documented case of widespread mercury ingestion and subsequent fetal development complication took place in the 1950s in Minamata Bay, Japan. Used by a nearby industrial plant in the manufacture of plastics, methyl mercury was discharged into the waters of Minamata Bay, where it went on to be ingested regularly by many villagers who used the fish living in the bay as a dietary staple. Soon, many of the inhabitants who had been consuming the mercury-laden meat began experiencing negative effects from ingesting the toxin; however, the mercury especially impacted pregnant women and their fetuses, resulting in a high rate of miscarriage. Surviving infants exposed to mercury in-utero had extremely high rates of physical and mental handicaps, as well as physical abnormalities from exposure in the womb during key stages in fetal physical development. The United States Food and Drug Administration and the Environmental Protection Agency advise pregnant women not to eat swordfish, shark, king mackerel and tilefish and limit consumption of albacore tuna to 6 ounces or less a week.
Mercury exposure in pregnancy may also cause limb defects.
The developing nervous system of the fetus is particularly vulnerable to lead toxicity. Neurological toxicity is observed in children of exposed women as a result of the ability of lead to cross the placental barrier. A special concern for pregnant women is that some of the bone lead accumulation is released into the blood during pregnancy. Several studies have provided evidence that even low maternal exposures to lead produce intellectual and behavioral deficits in children.
Dioxins and dioxin-like compounds persists in the environment for a long time and are widespread, so all people have some amount of dioxins in the body. Intrauterine exposure to dioxins and dioxin-like compounds have been associated with subtle developmental changes on the fetus. Effects on the child later in life include changes in liver function, thyroid hormone levels, white blood cell levels, and decreased performance in tests of learning and intelligence.
Compounds such as carbon monoxide, sulfur dioxide and nitrogen dioxide all have the potential to cause serious damage when inhaled by an expecting mother. Low birth weight, preterm birth, intrauterine growth retardation, and congenital abnormalities have all been found to be associated with fetal exposure to air pollution. Although pollution can be found virtually everywhere, there are specific sources that have been known to release toxic substances and should be avoided if possible by those who wish to remain relatively free of toxins. These substances include, but are not limited to: steel mills, waste/water treatment plants, sewage incinerators, automotive fabrication plants, oil refineries, and chemical manufacturing plants.
Control of air pollution can be difficult. For example, in Los Angeles, regulations have been made to control pollution, by putting rules on industrial and vehicle emissions. Improvements have been made to meet these regulations. Despite these improvements, the region still does not meet federal standards for ozone and particulate matter. Approximately 150,000 births occur every year in Los Angeles. Thus, any effects air pollution has on human development in utero are of great concern to those who live in this region.
Particulate matter (PM) consist of a mixture of particle pollutants that remain in the air, and vary be region. These particles are very small, ranging from PM10 to PM 2.5, which can easily enter the lungs. Particulate matter has been shown to be associated with acute cardio-respiratory morbidity and mortality. Intrauterine growth has been shown to be affected by particulate matter, leading to unhealthy outcomes for fetal development such as poor or slow fetal growth, and increasing fetal morbidity and mortality. A study from 2012 found that exposures to PM 2.5 differed by race/ethnicity, age, as well as socioeconomic status, leading to certain populations experiencing greater negative health outcomes due to environmental pollution, especially relating to particulate matter.
Pesticides are created for the specific purpose of causing harm (to insects, rodents, and other pests), pesticides have the potential to serious damages to a developing fetus, should they be introduced into the fetal environment. Studies have shown that pesticides, particularly fungicides, have shown up in analyses of infant's cord blood, proving that such toxins are indeed transferred into the baby's body. Overall, the two pesticides most frequently detected in cord blood are diethyltoluamide (DEET) and vinclozolin (a fungicide). Although pesticide toxicity is not as frequently mentioned as some of the other methods of environmental toxicity, such as air pollution, contamination can occur at any time from merely engaging in everyday activities such as walking down a pathway near a contaminated area, or eating foods that have not been washed properly. In 2007 alone, 1.1 billion pounds of pesticides were found present in the environment, causing pesticide exposure to gain notoriety as a new cause of caution to those wishing to preserve their health.
A 2013 review of 27 studies on prenatal and early childhood exposures to organophosphate pesticides found all but one showed negative neurodevelopmental outcomes. In the ten studies that assessed prenatal exposure, "cognitive deficits (related to working memory) were found in children at age 7 years, behavioral deficits (related to attention) seen mainly in toddlers, and motor deficits (abnormal reflexes), seen mainly in neonates."
A systematic review of neurodevelopmental effects of prenatal and postnatal organophosphate pesticide exposure was done in 2014. The review found that "Most of the studies evaluating prenatal exposure observed a negative effect on mental development and an increase in attention problems in preschool and school children."
In 2017, a study looked at the possible effects of agricultural pesticides in over 500,000 births in a largely agricultural region of California and compared their findings to birth outcomes in other less agriculturally dominated California areas. Overall, they found that pesticide exposure increased adverse birth outcomes by 5–9%, but only among those mothers exposed to the highest quantities of pesticides. 
Benzene exposure in mothers has been linked to fetal brain defects especially neural tube defects. In one study, BTEX (Benzene, toluene, ethylbenzene, xylenes) exposure during the first trimester of pregnancy has been clearly indicating negative association with biparietal brain diameter between 20 and 32 weeks of pregnancy. Women with high exposure to toluene had three to five times the miscarriage rate of those with low exposure, and women with occupational benzene exposure have been shown to have an increased rate of miscarriages. Paternal occupational exposure to toluene and formaldehyde has also been linked to miscarriage in their partners. Normal development is highly controlled by hormones, and disruption by man made chemicals can permanently change the course of development. Ambient ozone has been negatively associated with sperm concentration in men, chemicals associated with UOG operations (e.g., benzene, toluene, formaldehyde, ethylene glycol and ozone) have been associated with negative impacts on semen quality, particularly reduced sperm counts.
A 2011 study found a relationship between Neural Tube Defects and maternal exposure to benzene, a compound associated with natural gas extraction. The study found that mothers living in Texas census tracts with higher ambient benzene levels were more likely to have offspring with neural tube defects, such as spina bifida, than mothers living in areas with lower benzene levels.
- Heat and noise have also been found to have significant effects on development.
- Carbon dioxide – decreased oxygen delivery to brain, intellectual deficiencies
- Ionizing radiation – miscarriage, low birth weight, physical birth defects, childhood cancers
- Environmental exposure to perchlorate in women with hypothyroidism causes a significant risk of low IQ in the child.
Avoiding relevant environmental toxins in pregnancy
The American College of Nurse-Midwives recommends the following precautions to minimize exposure to relevant environmental toxins in pregnancy:
- Avoiding paint supplies such as stained glass material, oil paints and ceramic glazes, and instead using watercolor or acrylic paints and glazes.
- Checking the quality of the tap water or bottled water and changing water drinking habits if necessary.
- If living in a home built before 1978, checking whether lead paint has been used. If such is the case, paint that is crumbling or peeling should not be touched, a professional should remove the paint and the site should be avoided while the paint is removed or sanded.
- To decrease exposure to pesticides; washing all produce thoroughly, peeling the skin from fruits and vegetables or buying organic produce if possible.
- Avoiding any cleaning supply labeled "toxic" or any product with a warning on the label, and instead trying natural products, baking soda, vinegar and/or water to clean.
Natural gas development
In a rural Colorado study of natural gas development, maternal residence within a 10-mile radius of natural gas wells was found to have a positive association to the prevalence of congenital heart defects (CHDs) and neural tube defects (NTDs). Along with this finding, a small association was found between mean birth weight and the density and proximity to the natural gas wells. Maternal exposure through natural gas wells may come in the form of benzene, solvents, polycyclic aromatic hydrocarbons (PAHs), and other air pollutants such as toluene, nitrogen dioxide, and sulfur dioxide.
In Pennsylvania, unconventional natural gas producing wells increased from zero in 2005 to 3689 in 2013. A 2016 study of 9384 mothers and 10946 neonates in the Geisinger Health System in Pennsylvania found prenatal residential exposure to unconventional natural gas development activity was associated with preterm birth and physician-recorded high-risk pregnancy. In Southwest Pennsylvania, maternal proximity to unconventional gas drilling has been found to be associated with decreased birth weight. It was unclear which route of exposure: air, soil or water could be attributed to the association. Further research and larger studies on this topic are needed.
Endocrine disruptors are compounds that can disrupt the normal development and normal hormone levels in humans. Endocrine-disrupting chemicals (EDCs) can interact with hormone receptors, as well as change hormone concentrations within the body, leading to incorrect hormone responses in the body as well as disrupt normal enzyme functioning. Oil and gas extraction has been known to contribute to EDCs in the environment, largely due to the high risk of ground and surface water contamination that comes with these extractions. In addition to water contamination, oil and gas extraction also lead to higher levels of air pollution, creating another route of exposure for these endocrine disruptors. This problem often goes under-reported, and therefore, the true magnitude of the impact is underestimated. In 2016, a study was conducted to assess the need for an endocrine component to health assessments for drilling and extraction of oil and gas in densely populated areas. With the high potential for release of oil and gas chemicals with extraction, specifically chemicals that have been shown to disrupt normal hormone production and function, the authors highly emphasized the need for a component centering around endocrine function and overall health with health assessments, and how this in turn impacts the environment.
Role of the placenta
The healthy placenta is a semipermeable membrane that does form a barrier for most pathogens and for certain xenobiotic substances. However, it is by design an imperfect barrier since it must transport substances required for growth and development. Placental transport can be by passive diffusion for smaller molecules that are lipid soluble or by active transport for substances that are larger and/or electrically charged. Some toxic chemicals may be actively transported. The dose of a substance received by the fetus is determined by the amount of the substance transported across the placenta as well as the rate of metabolism and elimination of the substance. As the fetus has an immature metabolism, it is unable to detoxify substances very efficiently; and as the placenta plays such an important role in substance exchange between the mother and the fetus, it goes without saying that any toxic substances that the mother is exposed to are transported to the fetus, where they can then affect development. Carbon-dioxide, lead, ethanol (alcohol), and cigarette smoke in particular are all substances that have a high likelihood of placental transferral.
Identifying potential hazards for fetal development requires a basis of scientific information. In 2004, Brent proposed a set of criteria for identifying causes of congenital malformations that also are applicable to developmental toxicity in general. Those criteria are:
- Well-conducted epidemiology studies consistently show a relationship between particular effects and exposure to the substance.
- Data trends support a relationship between changing levels of exposure and the specific effect.
- Animal studies provide evidence of the correlation between substance exposures and particular effects.
- Woodruff, T. J.; Zota, A. R.; Schwartz, J. M. (2011). "Environmental Chemicals in Pregnant Women in the United States: NHANES 2003–2004". Environmental Health Perspectives. 119 (6): 878–885. doi:10.1289/ehp.1002727. PMC 3114826. PMID 21233055.
- Pohl, Hana R.; Smith-Simon, Cassandra; Hicks, Heraline (1998). "Health Effects Classification and Its Role in the Derivation of Minimal Risk Levels: Developmental Effects". Regulatory Toxicology and Pharmacology. 28 (1): 55–60. doi:10.1006/rtph.1998.1232. PMID 9784433.
- Lanphear, Bruce P.; Vorhees, Charles V.; Bellinger, David C. (2005). "Protecting Children from Environmental Toxins". PLoS Medicine. 2 (3): e61. doi:10.1371/journal.pmed.0020061. PMC 1069659. PMID 15783252.
- "teratogen". dictionary.com. Retrieved 4 October 2013.
- Daftary, Shirish; Chakravarti, Sudip (2011). Manual of Obstetrics, 3rd Edition. Elsevier. pp. 38-41. ISBN 9788131225561.
- Wing L.; Potter D. (2002). "The epidemiology of autistic spectrum disorders: is the prevalence rising?". Mental Retardation and Developmental Disabilities Research Reviews. 8: 151–161. doi:10.1002/mrdd.10029. PMID 12216059.
- ATSDR (January 17, 2013). "Principles of Pediatric Environmental Health: How Can Parents' Preconception Exposures and In Utero Exposures Affect a Developing Child?". Centers for Disease Control and Prevention.
- "Facts About FASDs". Alcohol Use in Pregnancy | FASD | NCBDDD | CDC. 9 August 2017.
- Hackshaw, A; Rodeck, C; Boniface, S (Sep–Oct 2011). "Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls". Human Reproduction Update. 17 (5): 589–604. doi:10.1093/humupd/dmr022. PMC 3156888. PMID 21747128.
- Abelsohn, A; Vanderlinden, LD; Scott, F; Archbold, JA; Brown, TL (January 2011). "Healthy fish consumption and reduced mercury exposure: counseling women in their reproductive years". Canadian Family Physician. 57 (1): 26–30. PMC 3024155. PMID 21322285.
- Burt Susan D (1986). "Mercury Toxicity, An Overview". AAOHN Journal. 34 (11): 543–546.
- Manduca, Paola, Awny Naim, and Simona Signoriello. "Specific Association of Teratogen and Toxicant Metals in Hair of Newborns with Congenital Birth Defects or Developmentally Premature Birth in a Cohort of Couples with Documented Parental Exposure to Military Attacks: Observational Study at Al Shifa Hospital, Gaza, Palestine." International Journal of Environmental Research and Public Health. N.p., 14 May 2014. Web. 25 July 2014. <http://www.mdpi.com/journal/ijerph>.
- "Chapter 1, Lead-based Paint Hazards, 98–112". Cdc.gov. Archived from the original on 29 October 2011. Retrieved 25 November 2011.
- Facts about Dioxins. Archived 2019-02-02 at the Wayback Machine from Minnesota Department of Health. Updated October 2006
- Backes, CH; Nelin, T; Gorr, MW; Wold, LE (Jan 10, 2013). "Early life exposure to air pollution: how bad is it?". Toxicology Letters. 216 (1): 47–53. doi:10.1016/j.toxlet.2012.11.007. PMC 3527658. PMID 23164674.
- Le, Hien Q.; Batterman, Stuart A.; Wirth, Julia J.; Wahl, Robert L.; Hoggatt, Katherine J.; Sadeghnejad, Alireza; Hultin, Mary Lee; Depa, Michael (2012). "Air pollutant exposure and preterm and term small-for-gestational-age births in Detroit, Michigan: Long-term trends and associations". Environment International. 44: 7–17. doi:10.1016/j.envint.2012.01.003. PMC 4331339. PMID 22314199.
- Minguillón, M.C.; Schembari, A.; Triguero-Mas, M.; de Nazelle, A.; Dadvand, P.; Figueras, F.; Salvado, J.A.; Grimalt, J.O.; Nieuwenhuijsen, M.; Querol, X. (2012). "Source apportionment of indoor, outdoor and personal PM2.5 exposure of pregnant women in Barcelona, Spain". Atmospheric Environment. 59: 426–36. Bibcode:2012AtmEn..59..426M. doi:10.1016/j.atmosenv.2012.04.052.
- Ritz, Beate; Wilhelm, Michelle (2008). "Air Pollution Impacts on Infants and Children". Southern California Environmental Report Card. UCLA Institute of the Environment and Sustainability.
- Dejmek J., Selevan S. G., Benes I., Solansky I., Sram R. J. (1999). "Fetal Growth and Maternal Exposure to Particulate Matter during Pregnancy". Environmental Health Perspectives. 107 (6): 475–80. doi:10.2307/3434630. JSTOR 3434630. PMC 1566587. PMID 10339448.CS1 maint: multiple names: authors list (link)
- Bell M., Ebisu K. (2012). "Environmental Inequality in Exposures to Airborne Particulate Matter Components in the United States". Environmental Health Perspectives. 120 (12): 1699–1704. doi:10.1289/ehp.1205201. JSTOR 23323098. PMC 3546368. PMID 22889745.
- Wickerham, Erin L.; Lozoff, Betsy; Shao, Jie; Kaciroti, Niko; Xia, Yankai; Meeker, John D. (2012). "Reduced birth weight in relation to pesticide mixtures detected in cord blood of full-term infants". Environment International. 47: 80–5. doi:10.1016/j.envint.2012.06.007. PMC 3410737. PMID 22796478.
- Muñoz-Quezada MT, Lucero BA, Barr DB, Steenland K, Levy K, Ryan PB, Iglesias V, Alvarado S, Concha C, Rojas E, Vega C (2013). "Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: a systematic review". Neurotoxicology. 39: 158–68. doi:10.1016/j.neuro.2013.09.003. PMC 3899350. PMID 24121005.CS1 maint: multiple names: authors list (link)
- González-Alzaga B, Lacasaña M, Aguilar-Garduño C, Rodríguez-Barranco M, Ballester F, Rebagliato M, Hernández AF (2014). "A systematic review of neurodevelopmental effects of prenatal and postnatal organophosphate pesticide exposure". Toxicol Lett. 230: 104–21. doi:10.1016/j.toxlet.2013.11.019. PMID 24291036.CS1 maint: multiple names: authors list (link)
- Larsen, Ashley; Gaines, Steven (2017-08-29). "Agricultural pesticide use and adverse birth outcomes in the San Joaquin Valley of California". Nature Communications. 8 (1): 302. doi:10.1038/s41467-017-00349-2. ISSN 2041-1723. PMC 5575123. PMID 28851866.
- Webb E., Bushkin-Bedient S., Cheng A., Kassotis C. D., Balise V., Nagel S. C. (2014). "Developmental and reproductive effects of chemicals associated with unconventional oil and natural gas operations". Reviews on Environmental Health. 29 (4): 307–18. doi:10.1515/reveh-2014-0057. PMID 25478730.CS1 maint: multiple names: authors list (link)
- Lupo P. J., Symanski E., Waller D. K., Chan W., Langlois P. H., Canfield M. A., Mitchell L. E. (2010). "Maternal Exposure to Ambient Levels of Benzene and Neural Tube Defects among Offspring: Texas, 1999–2004". Environmental Health Perspectives. 119 (3): 397–402. doi:10.1289/ehp.1002212. PMC 3060005. PMID 20923742.CS1 maint: multiple names: authors list (link)
- Lazarus, J. H. "Controlled Antenatal Thyroid Screening study". ISRCTN. doi:10.1186/ISRCTN46178175.. Also described in Medscape article: Perchlorate Levels in Pregnancy Linked to Low Childhood IQ, by Nancy A. Melville, October 22, 2013
- Environmental Hazards During Pregnancy Volume 51, No. 1, January/February 2006.
- McKenzie LM, Guo R, Witter RZ, Savitz DA, Newman LS, Adgate JL (2014). "Birth outcomes and maternal residential proximity to natural gas development in rural Colorado". Environ Health Perspect. 122: 412–417. doi:10.1289/ehp.1306722. PMC 3984231. PMID 24474681.
- Casey J. A., Savitz D. A., Rasmussen S. G., Ogburn E. L., Pollak J., Mercer D. G., Schwartz B. S. (2015). "Unconventional Natural Gas Development and Birth Outcomes in Pennsylvania, USA". Epidemiology. 27: 163–72. doi:10.1097/ede.0000000000000387. PMC 4738074. PMID 26426945.CS1 maint: multiple names: authors list (link)
- Stacy S. L., Brink L. L., Larkin J. C., Sadovsky Y., Goldstein B. D., Pitt B. R., Talbott E. O. (2015). "Perinatal Outcomes and Unconventional Natural Gas Operations in Southwest Pennsylvania". PLoS ONE. 10 (6): e0126425. doi:10.1371/journal.pone.0126425. PMC 4454655. PMID 26039051.CS1 maint: multiple names: authors list (link)
- Kassotis CD, Tillitt DE, Lin CH, McElroy JA, Nagel SC (2016). "Endocrine- disrupting chemicals and oil and natural gas operations: potential environmental contamination and recommendations to assess complex environmental mixtures" (PDF). Environ Health Perspect. 124: 256–264. doi:10.1289/ehp.1409535. PMC 4786988. PMID 26311476.
- Brent, Robert L. (2004). "Environmental causes of human congenital malformations: The pediatrician's role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors". Pediatrics. 113 (4 Suppl): 957–68. PMID 15060188.
- Agin, Dan (2009). More Than Genes: What Science Can Tell Us About Toxic Chemicals, Development, and the Risk to Our Children. New York: Oxford University Press. ISBN 978-0-19-538150-4.
- Buelke-Sam, Judy; Kimmel, Carol A., eds. (1994). Developmental Toxicology (2nd ed.). New York: Raven Press. ISBN 0-7817-0137-6.
- Chudley, T. V. N.; Persaud, A. E.; Skalko, Richard G. (1985). Basic Concepts in Teratology. New York: Alan R. Liss. ISBN 0-8451-0241-9.
- Schardein, James L., ed. (2000). Chemically Induced Birth Defects (3rd ed.). New York: Marcel Dekker. ISBN 0-8247-0265-4.
- Steingraber, Sandra (2001). Having Faith: An Ecologist's Journey to Motherhood. Cambridge, MA: Perseus Publishing. ISBN 1-903985-14-5.