Biology:Reproductive toxicity

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Short description: Hazard associated with chemical substances

The international pictogram for chemicals that are sensitising, mutagenic, carcinogenic or toxic to reproduction

Reproductive toxicity refers to the potential risk from a given chemical, physical or biologic agent to adversely affect both male and female fertility as well as offspring development.[1] Reproductive toxicants may adversely affect sexual function, ovarian failure, fertility as well as causing developmental toxicity in the offspring.[2][3] Lowered effective fertility related to reproductive toxicity relates to both male and female effects alike and is reflected in decreased sperm counts, semen quality and ovarian failure.

Infertility

Infertility is medically defined as a failure of a couple to conceive over the course of one year of unprotected intercourse.[4] Primary infertility indicates that a person has never been able to achieve pregnancy while secondary infertility is defined as a person having at least one pregnancy before.[5] As many as 20% of couples experience infertility.[4] Infertility may be caused by an issue along any part of the process of fertilizing an egg through birth of the child. This can include: the release of the egg, the ability of the sperm to fertilize the egg, the implantation of the egg in the uterine wall, and the ability of the fetus to complete development without miscarriage.[6] Among males oligospermia is defined as a paucity of viable spermatozoa in the semen, whereas azoospermia refers to the complete absence of viable spermatozoa in the semen.[4] Males may also experience issues in sperm motility and morphology, which means the sperm are less likely to make it to the egg or to be able to fertilize the egg.[6] Female infertility could be a result of an issue regarding their uterus, ovaries, or fallopian tubes and can be affected by various diseases, endocrine/hormone disruption, or reproductive toxicant.[6][5]

The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) separates reproductive toxicity from germ cell mutagenicity and carcinogenicity, even though both these hazards may also affect fertility.[7]

Effects

Many drugs can affect the human reproductive system. Their effects can be

However, most studies of reproductive toxicity have focused on occupational or environmental exposure to chemicals and their effects on reproduction. Both consumption of alcohol and tobacco smoking are known to be "toxic for reproduction" in the sense used here.

One well-known group of substances which are toxic for reproduction are teratogens – substances which cause birth defects. (S)-thalidomide is possibly the most notorious of these.[8]

Another group of substances which have received much attention (and prompted some controversy) as possibly toxic for reproduction are the so-called endocrine disruptors.[8] Endocrine disruptors change how hormones are produced and how they interact with their receptors.[9] Endocrine disruptors are classified as estrogenic, anti-estrogenic, androgenic or anti-androgenic. Each category includes pharmaceutical compounds and environmental compounds. Estrogenic or androgenic compounds will cause the same hormonal responses as the sex steroids (estrogen and testosterone). However anti-estrogenic and anti-andogenic compounds bind to a receptor and block the hormones from binding to their receptors, thus preventing their function. A few examples of the many types of endocrine disruptors are trenbolone (androgenic), flutamide (anti-androgenic), diethylstilbestrol (estrogenic), bisphenol A (estrogenic) and tributyltin (anti-estrogenic).[10][11]

However, many substances which are toxic for reproduction do not fall into any of these groups: lead compounds, for example, are considered to be toxic for reproduction[10][11] given their adverse effects on the normal intellectual and psychomotor development of human babies and children.

Examples

Heavy metals

Lead

A piece of dark black metallic substance representing elemental lead.
Elemental lead

Lead, a heavy metal that can exist in both organic and inorganic forms, and is associated with adverse effects on male libido, erectile disfunction, premature ejaculation and poor sperm quality.[12] Lead is also associated with negative effects on the female reproductive system particularly for pregnant women.[13] Elevated blood lead levels can increase risk of preeclampsia and miscarriage and can lead to birth defects.[14][15] Lead is believed to predominantly affect male reproduction by the disruption of hormones, which reduces the quantity of sperm production in the seminiferous tubules. It has also been proposed that lead causes poor semen quality by promoting the generation of reactive oxygen species such as hydrogen peroxide due to lipid peroxidation, which can cause cellular damage.[16][17] Lead can be found in contaminated soil, water, as well as manufactured goods like jewelry, toys, and paint.[18] Common routes of exposure are inhalation and digestion, though dermal exposure can occur albeit less frequently.[18] Occupational exposures remain a high risk, particularly for industries such as battery/electronic recycling, construction, mining, smelting, and welders or any other industry which interacts with lead.[13] Families and cohabitants of the above workers may be at risk of take-home exposure and may need to take precautions to avoid reproductive effects.[19]

Cadmium

A picture of a piece of elemental cadmium it is a hard metallic lustrous metal.
Elemental cadmium.

Cadmium is a heavy metal used in jewelry making, electronics, welding and galvanizing steel.[20] The human route of exposure is primarily inhalational or oral; environmental exposure among the non-occupationally exposed can occur due to exposure to cigarette smoking.[20] The oral route of exposure can occur due to ingesting plants and shellfish that have taken up cadmium from water and soil.[20] Exposure to cadmium results in adverse male fertility in terms of decreased spermatogenesis, semen quality, sperm motility and impaired hormonal synthesis.[21] Likewise, exposure to cadmium impairs female fertility in terms of menstrual cycle regularity and reproductive hormonal balance.[21] Cadmium exposure can negatively affect fetal development throughout the gestation as well as ovulation and implantation.[22]

Chromium

Hexavalent chromium ( Cr VI) is used in the electronics industry and for metal plating.[23] Chromium exposure is primarily inhalation or through ingestion.[24] Human and animal studies show that exposure to hexavalent chromium decreases semen quality and sperm counts.[25]

Mercury

Elemental mercury( Hg0) is a metal that exists as liquid form at room temperature and is commonly found in thermometers, blood pressure cuffs and dental amalgams. In terms of exposure, the route of absorption is primarily via inhalation through mercury vapor, which can in turn lead to mercury poisoning.[26] Occupational exposure to inorganic mercury can occur in industries such as dentistry, fluorescent lamp production, and Chloralkali workers.[27] Data among female dental technicians exposed to mercury vapors have demonstrated decreased fertility among those who were exposed and practiced poor industrial hygiene while handling dental amalgams.[26][28] Elemental and organic mercury can cross the blood brain barrier, like many other heavy metals, making it particularly significant for pregnant women as it can affect fetal development and birth outcomes.[27] Among female workers in mercury smelting plants an increase in spontaneous abortions has been reported.[28]

Picture of silvery metal showing chromium.
Elemental chromium.

Dibromochloropropane

Dibromochloropropane (DBCP) is used as a pesticide against nematodes in the agricultural industry.[29] DBCP is one of the most well-known reproductive toxicants known to cause testicular toxicity.[12] Workers in chemical factories exposed to dibromochloropropane have been shown to develop dose-dependent oligospermia and azoospermia.[12] Additional studies also demonstrated that DBCP-exposed workers in banana and pineapple plantations in Central America and other countries also developed oligospermia and azoospermia.[30] In 1977, the United States Environmental Protection Agency banned the use of DBCP in agriculture due to its effect on male fertility.[31] Despite being banned from use in agriculture, DBCP is still used as an intermediate in chemical manufacturing as well as a reagent in research.[31]

Ethylene dibromide

Ethylene dibromide (EDB) is a fumigant that was originally used to protect citrus fruits, grains and vegetables from insects.[32] Use of EDB in the United States was banned by the United States Environmental Protection Agency in 1984, however EDB is still used in the United States as fumigant to treat timber logs for beetles and termites.[32] Likewise, it is still used as an intermediate in chemical manufacturing.[32] Exposure to EDB has been shown to adversely affect male fertility by leading to a decreased sperm counts, decreased numbers of viable sperm and increased abnormal sperm morphology.[33][34] The primary route of exposure is through inhalation.[32]

Industrial solvents

Solvent exposure is common among men and women working in industrial settings. Specific solvents including xylene, perchloroethylene, toluene and methylene chloride have been shown to be associated with a concurrent elevation in risk for spontaneous abortion [35]

Ionizing radiation

Ionizing radiation in the form alpha, beta and gamma emissions are well known to adversely affect male and female fertility, as well as fetal development.[36][37] Exposure to low doses of ionizing radiation can occur naturally in the environment or due to medical treatment or diagnosis, however, higher exposures may be associated with occupation.[36] Occupations with documented risk include: healthcare workers who interact with radioactive material, certain manufacturing processes, and airline personnel.[36] Exposure in the range of 0.1 to1.2 Gy is associated with spermatogonial injury; whereas between 4-6 Gy reductions of sperm counts have been reported.[37] Ionizing radiation is considered a hazard particularly in pregnancy, due to its potential effect of gestational development.[36] More specifically, ionizing radiation is associated with an increased risk of miscarriage and stillbirth.[38] Recent studies suggest that routine medical examinations that expose a pregnant person to ionizing radiation are not associated with an increase of risk of miscarriage or stillbirth.[39]

Radio frequency electromagnetic fields

Radio frequency electromagnetic fields, such as those generated from mobile phone devices, have been shown to decrease semen quality production in experimental animal models; however human data is still equivocal at best.[40][41] The International Association for the Research of Cancer(IARC) classifies radio frequency electromagnetic fields as a group 2B or possibly carcinogenic.[42]

Endocrine disrupting compounds

Lipid soluble compounds that can cross the cell lipid bilayer and bind cytoplasmic steroid hormone receptors can translocate to the nucleus and act as estrogen agonists.[43] Diethylstilbestrol (DES), a synthetic estrogen, is one such endocrine disruptor and acts as an estrogen agonist. Diethylstilbestrol was used from 1938 to 1971 to prevent spontaneous abortions.[43] Diethylstilbestrol causes cancer and mutations by producing highly reactive metabolites, also causing DNA adducts to form. Exposure to diethylstilbestrol in the womb can cause atypical reproductive tract formation. Specifically, females exposed to diethylstilbestrol in utero during the first trimester have are more likely to develop clear cell vaginal carcinoma, and males have an increased risk of hypospadias.[44]

Bisphenol A

Hexagonal representation of the line drawing of a chemical structure of bisphenol A.
The chemical structure of bisphenol A.

Bisphenol A (BPA) is used in polycarbonate plastic consumer goods and aluminum can liners.[45] BPA is an example of an endocrine disruptor which negatively affects reproductive development by acting as an estrogen mimicker (xenoestrogen) and a likely androgen mimicker.[46] Bisphenol A exposure in fetal female rats leads to mammary gland morphogenesis, increased formation of ovarian tumors, and increased risk of developing mammary gland neoplasia in adult life. In lab animal models, BPA is considered to be both an ovarian and uterine toxicant as it impairs endometrial proliferation, decreases uterine receptivity and decreases the chances for successful implantation of the embryo [47] The adverse reproductive toxicological effects of bisphenol A have been better studied in females than in males.[48][49][47]

Antineoplastic Drugs (Chemotherapy)

Antineoplastic drugs, commonly known as chemotherapy drugs, are considered hazardous drugs by the CDC, including hazardous to reproductive health.[50] Exposure to chemotherapy drugs most often occurs through treatment for cancer, however, unintentional occupational exposure may occur in for workers involved in pharmaceutical production, pharmacists or technicians preparing the drugs, and nurses or other healthcare professionals who are administering medication to patients.[51] Other hospital staff, particularly custodial workers, who interact or handle antineoplastic drugs in any capacity may also be at risk of exposure.[51] Exposure can occur through inhalation, skin contact, ingestion, or injection.[51]

Non-Chemical Toxicants

Work Schedule

Work schedule can become a reproductive toxicant when working hours are during the employee's typical sleeping hours (night shift), when a worker has an irregular work schedule (shift work) or long working hours.[52] Work schedule's reproductive toxicity is primarily a result of effect on regularity, quality, and rhythm of sleep.[52] Shift work is associated with menstrual disorders, which can in turn affect fertility.[52][53] Irregular work schedule, working long hours, and working the night shift is associated with an increased risk of miscarriage and pre-term birth.[52] Many occupations engage in shift work, including requiring rotating work schedules, long hours, or night shift work. Some occupations that frequently engage in shift work include first responders, airline personnel, healthcare workers, and service workers.[52] The CDC estimates that fifteen-million Americans engage in shift work and 30% get less than six-hours of sleep.[52]

Physical Demands

Physical demands can include bending, lifting, and standing. Physical demands are considered a reproductive toxicant as they can increase the risk of adverse outcomes during pregnancy.[54] Bending, lifting, and standing are often associated with occupational responsibilities as the risk is minimal unless physical activity is prolonged.[54] Standing and walking for more than three hours a day is associated with an increased risk of pre-term birth, while standing for six to eight hours a day is associated with an increased risk of miscarriage.[55][56] The weight and frequency of lifting is also associated with increased risk of miscarriage and preterm birth, with estimates of loads over 10 kg, or frequency a cumulative 100 kg/day.[56][57]

Noise

Noise is considered a reproductive toxicant due to its potential effect on fetal development during pregnancy. While pregnant women may be able to use proper hearing protection to conserve their own hearing, after the 20th week of development babies' ears are susceptible to hearing loss.[58] Pregnant women who are past 20 weeks of development should consider avoiding noises above 85 decibels, including at work and recreational activities.[58]

See also

References

  1. ↑ Occupational Health and Safety Administration. "Reproductive Hazards". https://www.osha.gov/reproductive-hazards. 
  2. ↑ "Regulation (EC) No 1272/2008 of the EUROPEAN PARLIAMENT and of the COUNCIL". Official Journal of the European Union. 16 December 2008. https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:353:0001:1355:EN:PDF. "Annex I, section 3.7 labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006.". 
  3. ↑ International Programme on Chemical Safety (2001). "Principles For Evaluating Health Risks To Reproduction Associated With Exposure To Chemicals". Environmental Health Criteria (Geneva: World Health Organization) 225. http://www.inchem.org/documents/ehc/ehc/ehc225.htm. 
  4. ↑ 4.0 4.1 4.2 Current Medical Diagnosis & Treatment. McGraw Hill. 2022. 
  5. ↑ 5.0 5.1 "Infertility" (in en). https://www.who.int/news-room/fact-sheets/detail/infertility. 
  6. ↑ 6.0 6.1 6.2 "Infertility | CDC" (in en-us). 2023-04-26. https://www.cdc.gov/reproductivehealth/infertility/index.htm. 
  7. ↑ United Nations (2015-06-19) (in en). Globally Harmonized System of Classification and Labelling of Chemicals (GHS): Sixth Revised Edition. United Nations. doi:10.18356/591dabf9-en. ISBN 978-92-1-057320-7. https://www.un-ilibrary.org/content/books/9789210573207. 
  8. ↑ 8.0 8.1 International Programme on Chemical Safety (2002). "Global assessment of the state-of-the-science of endocrine disruptors". Geneva: World Health Organization. https://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/. 
  9. ↑ "Endocrine Disruptors" (in en). https://www.niehs.nih.gov/health/topics/agents/endocrine. 
  10. ↑ 10.0 10.1 Commission Directive 2004/73/EC of 29 August 2004 adapting to technical progress for the 29th time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. OJEC L152, 30.04.2004, pp. 1–311 (index no. 082-001-00-6).
  11. ↑ 11.0 11.1 Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. OJEC L353, 31.12.2008, pp. 1–1355 at p. 444 (index no. 082-001-00-6).
  12. ↑ 12.0 12.1 12.2 (in English) Current Diagnosis and Treatment: Occupational Medicine. United States: McGraw Hill Medical. 2014. pp. 455–459. ISBN 978-1-259-25145-0. 
  13. ↑ 13.0 13.1 "Lead & Other Heavy Metals - Reproductive Health | NIOSH | CDC" (in en-us). 2023-05-01. https://www.cdc.gov/niosh/topics/repro/heavymetals.html. 
  14. ↑ Zhong, Zixing; Yang, Qingmei; Li, Chu; Chen, Xiaohong; Zhou, Feifei (2022-12-23). "A global perspective of correlation between maternal blood lead levels and risks of preeclampsia: An updated systematic review and meta-analysis". Frontiers in Public Health 10. doi:10.3389/fpubh.2022.1072052. ISSN 2296-2565. PMID 36620238. 
  15. ↑ Kaur, Mandeep; Sharma, Priya; Kaur, Rajinder; Khetarpal, Preeti (2022-01-02). "Increased incidence of spontaneous abortions on exposure to cadmium and lead: a systematic review and meta-analysis" (in en). Gynecological Endocrinology 38 (1): 16–21. doi:10.1080/09513590.2021.1942450. ISSN 0951-3590. PMID 34169802. https://www.tandfonline.com/doi/full/10.1080/09513590.2021.1942450. 
  16. ↑ "How does lead induce male infertility?". Iranian Journal of Reproductive Medicine 9 (1): 1–8. 2011. PMID 25356074. 
  17. ↑ "Protective effects of Fumaria parviflora L. on lead-induced testicular toxicity in male rats". Andrologia 46 (4): 437–46. May 2014. doi:10.1111/and.12100. PMID 23611729. 
  18. ↑ 18.0 18.1 "Lead (Pb) Toxicity: What Are Routes of Exposure to Lead? | Environmental Medicine | ATSDR" (in en-us). 2023-05-25. https://www.atsdr.cdc.gov/csem/leadtoxicity/exposure_routes.html. 
  19. ↑ "Take-Home Exposures - Reproductive Health | NIOSH | CDC" (in en-us). 2023-05-01. https://www.cdc.gov/niosh/topics/repro/takehome.html. 
  20. ↑ 20.0 20.1 20.2 "Cadmium toxicity and treatment". TheScientificWorldJournal 2013. 2013. doi:10.1155/2013/394652. PMID 23844395. 
  21. ↑ 21.0 21.1 "Cadmium toxicity: effects on human reproduction and fertility". Reviews on Environmental Health 34 (4): 327–338. December 2019. doi:10.1515/reveh-2019-0016. PMID 31129655. 
  22. ↑ Thompson, J; Bannigan, J (April 2008). "Cadmium: Toxic effects on the reproductive system and the embryo" (in en). Reproductive Toxicology 25 (3): 304–315. doi:10.1016/j.reprotox.2008.02.001. PMID 18367374. https://linkinghub.elsevier.com/retrieve/pii/S0890623808000166. 
  23. ↑ "Impact of Environmental and Lifestyle Use of Chromium on Male Fertility: Focus on Antioxidant Activity and Oxidative Stress". Antioxidants 10 (9): 1365. August 2021. doi:10.3390/antiox10091365. PMID 34572997. 
  24. ↑ "Toxicity and carcinogenicity of chromium compounds in humans". Critical Reviews in Toxicology 36 (2): 155–163. February 2006. doi:10.1080/10408440500534032. PMID 16736941. 
  25. ↑ "Effect of Cr(VI) exposure on sperm quality: human and animal studies". The Annals of Occupational Hygiene 45 (7): 505–511. October 2001. doi:10.1016/S0003-4878(01)00004-7. PMID 11583652. 
  26. ↑ 26.0 26.1 "Mercury vapor and female reproductive toxicity". Toxicological Sciences 59 (2): 291–296. February 2001. doi:10.1093/toxsci/59.2.291. PMID 11158722. 
  27. ↑ 27.0 27.1 Bjørklund, Geir; Chirumbolo, Salvatore; Dadar, Maryam; Pivina, Lyudmila; Lindh, Ulf; Butnariu, Monica; Aaseth, Jan (October 2019). "Mercury exposure and its effects on fertility and pregnancy outcome" (in en). Basic & Clinical Pharmacology & Toxicology 125 (4): 317–327. doi:10.1111/bcpt.13264. ISSN 1742-7835. PMID 31136080. https://onlinelibrary.wiley.com/doi/10.1111/bcpt.13264. 
  28. ↑ 28.0 28.1 "Reproductive toxicity of occupational mercury. A review of the literature". Journal of Dentistry 27 (4): 249–256. May 1999. doi:10.1016/S0300-5712(97)00039-0. PMID 10193101. 
  29. ↑ "Dibromochloropropane (DBCP): a review". The Science of the Total Environment 17 (3): 207–221. March 1981. doi:10.1016/0048-9697(81)90062-0. PMID 7015501. Bibcode: 1981ScTEn..17..207B. 
  30. ↑ "Environmental Toxins and Men's Health: Dibromochloropropane". Effects of Lifestyle on Men's Health. 
  31. ↑ 31.0 31.1 Encyclopedia of Toxicology (Third ed.). Science Direct. 2014. 
  32. ↑ 32.0 32.1 32.2 32.3 "Ethylene Dibromide (Dibromoethane) Hazard Summary". https://www.epa.gov/sites/default/files/2016-09/documents/ethylene-dibromide.pdf. 
  33. ↑ Schrader, Steven M. (2003). "Man and the workplace". Chemical Health & Safety 10 (5): 11–16. doi:10.1016/s1074-9098(03)00089-3. 
  34. ↑ Ratcliffe, J. M.; Schrader, S. M.; Steenland, K.; Clapp, D. E.; Turner, T.; Hornung, R. W. (1 May 1987). "Semen quality in papaya workers with long term exposure to ethylene dibromide". Occupational and Environmental Medicine 44 (5): 317–326. doi:10.1136/oem.44.5.317. ProQuest 1771266376. PMID 3297130. 
  35. ↑ CURRENT Diagnosis & Treatment: Occupational & Environmental Medicine (6th ed.). McGraw Hill. 2021. 
  36. ↑ 36.0 36.1 36.2 36.3 "Radiation - Ionizing - Reproductive Health | NIOSH | CDC" (in en-us). 2023-05-01. https://www.cdc.gov/niosh/topics/repro/ionizingradiation.html. 
  37. ↑ 37.0 37.1 "Radiations and male fertility". Reproductive Biology and Endocrinology 16 (1). December 2018. doi:10.1186/s12958-018-0431-1. PMID 30445985. 
  38. ↑ Frangione, Brianna; Hinton, Patrick; Villeneuve, Paul J. (January 2023). "Low-dose ionizing radiation and adverse birth outcomes: a systematic review and meta-analysis" (in en). International Archives of Occupational and Environmental Health 96 (1): 77–92. doi:10.1007/s00420-022-01911-2. ISSN 0340-0131. PMID 35913560. Bibcode: 2023IAOEH..96...77F. 
  39. ↑ Lowe, Sandra A. (August 2020). "Ionizing radiation for maternal medical indications". Prenatal Diagnosis 40 (9): 1150–1155. doi:10.1002/pd.5592. ISSN 1097-0223. PMID 31697844. 
  40. ↑ "Biophysical evaluation of radiofrequency electromagnetic field effects on male reproductive pattern". Cell Biochemistry and Biophysics 65 (2): 85–96. March 2013. doi:10.1007/s12013-012-9414-6. PMID 22926544. 
  41. ↑ "Association between mobile phone use and semen quality: a systemic review and meta-analysis". Andrology 2 (4): 491–501. July 2014. doi:10.1111/j.2047-2927.2014.00205.x. PMID 24700791. 
  42. ↑ "Iarc Classifies Radiofrequency Electromagnetic Fields as Possibly Carcinogenic to Humans". International Agency for the Research in Cancer, World Health Organization. 31 May 2011. https://www.iarc.who.int/wp-content/uploads/2018/07/pr208_E.pdf. 
  43. ↑ 43.0 43.1 "Environmental toxicants and female reproduction". Fertility and Sterility 70 (4): 613–22. October 1998. doi:10.1016/s0015-0282(98)00253-2. PMID 9797086. 
  44. ↑ "Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study". Lancet (London, England) 359 (9312): 1102–7. March 2002. doi:10.1016/S0140-6736(02)08152-7. PMID 11943257. 
  45. ↑ "Bisphenol a and reproductive health: update of experimental and human evidence, 2007-2013". Environmental Health Perspectives 122 (8): 775–786. August 2014. doi:10.1289/ehp.1307728. PMID 24896072. 
  46. ↑ "In vivo effects of bisphenol A in laboratory rodent studies". Reproductive Toxicology 24 (2): 199–224. 2007. doi:10.1016/j.reprotox.2007.06.004. PMID 17683900. 
  47. ↑ 47.0 47.1 "Bisphenol A and human health: a review of the literature". Reproductive Toxicology 42: 132–155. December 2013. doi:10.1016/j.reprotox.2013.08.008. PMID 23994667. 
  48. ↑ "The Effects of Bisphenol A Exposure at Different Developmental Time Points in an Androgen-Sensitive Neuromuscular System in Male Rats". Endocrinology 157 (8): 2972–2977. August 2016. doi:10.1210/en.2015-1574. PMID 27022676. 
  49. ↑ "Environmental causes of cancer: endocrine disruptors as carcinogens". Nature Reviews. Endocrinology 6 (7): 363–370. July 2010. doi:10.1038/nrendo.2010.87. PMID 20498677. 
  50. ↑ (in en) NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. (Supersedes 2014-138). (Report). U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. 2016-09-01. doi:10.26616/nioshpub2016161. https://www.cdc.gov/niosh/docs/2016-161/. 
  51. ↑ 51.0 51.1 51.2 "Antineoplastic Agents: Hazardous Drug Exposures in Healthcare | NIOSH | CDC" (in en-us). 2020-02-20. https://www.cdc.gov/niosh/topics/hazdrug/antineoplastic.html. 
  52. ↑ 52.0 52.1 52.2 52.3 52.4 52.5 "Work Schedule - Reproductive Health | NIOSH | CDC" (in en-us). 2023-05-01. https://www.cdc.gov/niosh/topics/repro/workschedule.html. 
  53. ↑ Hu, Fengying; Wu, Cuiyun; Jia, Yunfei; Zhen, Hualong; Cheng, Hengshun; Zhang, Fan; Wang, Liuqing; Jiang, Minmin (December 2023). "Shift work and menstruation: A meta-analysis study" (in en). SSM - Population Health 24. doi:10.1016/j.ssmph.2023.101542. PMID 37954014. 
  54. ↑ 54.0 54.1 "Physical Demands (lifting, standing, bending) - Reproductive Health | NIOSH | CDC" (in en-us). 2023-05-01. https://www.cdc.gov/niosh/topics/repro/physicaldemands.html. 
  55. ↑ van Beukering, M. D. M.; van Melick, M. J. G. J.; Mol, B. W.; Frings-Dresen, M. H. W.; Hulshof, C. T. J. (November 2014). "Physically demanding work and preterm delivery: a systematic review and meta-analysis" (in en). International Archives of Occupational and Environmental Health 87 (8): 809–834. doi:10.1007/s00420-013-0924-3. ISSN 0340-0131. PMID 24390632. Bibcode: 2014IAOEH..87..809V. http://link.springer.com/10.1007/s00420-013-0924-3. 
  56. ↑ 56.0 56.1 Bonde, Jens Peter; Jørgensen, Kristian Tore; Bonzini, Matteo; Palmer, Keith T (July 2013). "Miscarriage and occupational activity: a systematic review and meta-analysis regarding shift work, working hours, lifting, standing, and physical workload" (in en). Scandinavian Journal of Work, Environment & Health 39 (4): 325–334. doi:10.5271/sjweh.3337. ISSN 0355-3140. PMID 23235838. PMC 3699369. http://www.sjweh.fi/show_abstract.php?abstract_id=3337. 
  57. ↑ Croteau, Agathe (July 2020). "Occupational lifting and adverse pregnancy outcome: a systematic review and meta-analysis" (in en). Occupational and Environmental Medicine 77 (7): 496–505. doi:10.1136/oemed-2019-106334. ISSN 1351-0711. PMID 32184210. https://oem.bmj.com/lookup/doi/10.1136/oemed-2019-106334. 
  58. ↑ 58.0 58.1 "Noise - Reproductive Health | NIOSH | CDC" (in en-us). 2023-05-01. https://www.cdc.gov/niosh/topics/repro/noise.html. 

Further reading



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