1 / 46

Reproductive and Developmental Toxicology

Reproductive and Developmental Toxicology. February 18, 2014 Sharon Huff, MD, MS. Learning Objectives. Be able to discuss general factors that may affect human reproduction as well as specific factors that are known to have adverse human reproductive and developmental effects

landen
Download Presentation

Reproductive and Developmental Toxicology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Reproductive and Developmental Toxicology February 18, 2014 Sharon Huff, MD, MS

  2. Learning Objectives • Be able to discuss general factors that may affect human reproduction as well as specific factors that are known to have adverse human reproductive and developmental effects • Be able to advise men and women relative to workplace reproductive hazards • Understand relevant regulatory issues such as those resulting from the US Supreme Court decision in U.A.W. vs. Johnson Controls • Be able to advise pregnant employees regarding workplace accommodations • Be aware of current environmental and consumer product concerns related to reproductive and developmental toxins and how women can protect themselves

  3. A larger and growing number of women of childbearing age are now working, many in traditional male occupations • 46.6% US workforce is women • 64% of working women are reproductive age • 52% of pregnant women work • 2 million births/year to working women

  4. http://www.cdc.gov/niosh/topics/repro/ • 2 million US couples infertile • 1/12 couples unable to conceive after 1 year of trying • 12% of couples report difficulty conceiving, 20% increase over past ten years (1995-2005) • Observed global trends in men's decreasing sperm counts • 50% overall decline in sperm count over past 50 years in Western countries counts • concerns about the role of chemicals encountered at work and in the environment at large • Overall contribution of occupational & environmental exposures to male and female infertility is unknown

  5. Social changes • Delay starting family career, education, financial goals • about 20% of women in the United States now have their first child after age 35 • Fertility declines with age • Genetic damage accumulations • Increases risks of cancers

  6. Less than half of all human conceptions result in birth of completely normal healthy infant

  7. Schematic illustration of the sensitive or critical periods in human development. Dark gray denotes highly sensitive periods; light gray indicates stages that are less sensitive Selevan SG, Kimmel CA, Mendola P. Identifying critical windows of exposure for children's health. Environ Health Perspect. 2000 Jun;108 Suppl 3:451-5.

  8. Females Evaluating Reproductive Capacity Males Semen analysis – sperm count, motility tests Endocrine / hormonal studies Fertility outcomes Anogenital distance • Endocrine / hormonal studies • Time to pregnancy • Fertility outcomes • Onset of menarche & puberty • Menstrual cycles

  9. Physical Agents • Ionizing Radiation Males: • Dose-related impairment of testicular function • Low dose 15-50 rads transient • >400 rads  permanent Females: • Exposure before or after birth can lead to permanent sterility from loss of ova • Endocrine abnormalities that cause infertility

  10. Physical Agents • Excessive Heat • Suppression of spermatogenesis • Hyperbaric environment • Decreases male fertility • Hypobaric environment • Impaired spermatogenesis, decreased birth rates, decreased weights at high altitudes

  11. Biological Agents • Mumps • Infection in the testes or ovaries can lead to sterility • Maternal infection in first trimester can cause spontaneous abortion • Varicella (Chicken Pox) • Congenital defects and risk of fetal mortality • Parvovirus • Miscarriage

  12. TORCH Infections Cause developmental abnormalities or stillbirth • Toxoplasmosis • Other infections caused by syphilis, hepatitis B, herpes zoster • Rubella • Cytomegalovirus • Herpes Simplex

  13. Chemical Agents • Carbon disulfide (viscose rayon) • Women: menstrual cycle changes • Men: sexual performance issues • Kepone (roach bait) • Decreased libido, altered sperm function / motility • DDT • Menstrual irregularities, prenatal exposure  polycystic ovarian disease later in life • DBCP • Targets spermatogenesis • Lead • Lowers sperm count, affects sperm morphology and motility • Mercury • Neurotoxic to fetus

  14. *** Classic Substances with the strongest associations for occupational exposure and poor pregnancy outcomes *** • Lead • Mercury • Ethylene Oxide • Ionizing radiation • Spontaneous abortion, miscarriage, birth defects

  15. MEN

  16. MEN

  17. Environmental Toxins linked to decreased sperm counts • Lead • Bisphenol-A • Phthaltes • Toluene • Pesticides • PCBs • Cigarette Smoke

  18. MEN • Store chemicals in sealed containers • Wash hands before eating, drinking, smoking • Avoid skin contact; follow directions for washing provided in MSDS • Avoid take home exposure • Attend safety training, follow safe practices, procedures, wear PPE

  19. Women

  20. Women • Video Display Terminals • No higher chance of reduced birth weight, preterm birth, or miscarriage • Agricultural Work • Mixing and applying herbicides (OR 27, 1.9-380) associated with infertility • Nightwork and Long Hours (>40 hours in 1st trimester)  increased risk of SAB • Health care workers: Hand hygiene and needle safety (infectious disease exposures) http://www.cdc.gov/niosh/topics/women/reproductive-health.html

  21. Women • Talk to doctor / nurse / safety before becoming pregnant • Look at chemicals worked with beforehand • Consider partner’s job / take home exposures • Good hand hygiene (HCW) and needle safety • Follow safety procedures, PPE, and avoid take home exposure • Store chemicals in sealed containers when they are not in use. • Wash hands after contact with hazardous substances and before eating, drinking, or smoking. • Avoid skin contact with chemicals.

  22. OSHA standards • Lead • Requires employer to annually train/inform on reproductive effects • Medical surveillance requires reproductive history • DBCP • Detailed reproductive medical surveillance exam (physical exam, reproductive hormone levels, semen analysis) • Ethylene dioxide • Hazcom label that states ‘reproductive hazard’ • Engineering design standards for hospitals • Medical surveillance with physical exam of reproductive system, pregnancy testing, and lab evaluation of fertility http://www.osha.gov/SLTC/reproductivehazards/

  23. The Pregnancy Discrimination Act (1978) • Cannot be fired or refused hire, demoted, or not promoted • Cannot be forced to take pregnancy leave or stop working • Must provide insurance, leave pay, other benefits given to ANY employee with medical leave or disability (15 or more employees) ** Pregnant employees must be treated the same as employees with any other temporary illness or medical condition ** • Example accommodations: modified tasks, alternate assignments, disability leave, or leave without pay • Employer can require medical documentation of duties she can and cannot perform http://www.eeoc.gov/laws/types/pregnancy.cfm

  24. Lead Men Women Spontaneous Abortions Stillbirths Neonatal Death Developmental abnormalities • Decreased sperm count • Increase in abnormal sperm morphology • Disruption of hypothalamic-pituitary-testicular axis • Chromosomal abnormalities

  25. Family Medical Leave Act • Employers (with 50 or more employees) must grant up to total 12 work weeks (unpaid) leave in 12 month period • Required to reinstate at same pay, same or equal job • Example: FMLA sick leave to work half days if having morning sickness http://www.eeoc.gov/laws/types/pregnancy.cfm

  26. Patient Protection and Affordable Care Act (“PPACA”) (signed March 23, 2010) • Amendment to Section 7 of Fair Labor Standards Act (1938) • Applies to employers with 50 or more employees Reasonable Break Time for Nursing Mothers • Required to provide breaks to express milk for 1 year • Required to provide place shielded from view and free from intrusion http://www.dol.gov/whd/regs/compliance/whdfs73.htm

  27. Genetic Information Nondiscrimination Act of 2008 (GINA) • prohibits genetic information discrimination in employment • Applies to any aspect of employment: • hiring, firing, pay, job assignments, promotions, layoffs, training, fringe benefits, or any other term or condition of employment • Employer cannot request, require or purchase genetic information • Genetic testing • Family genetic information • Family medical history • Genetic information of fetus carried by employee • Genetic information of fetus carried by a family member • Genetic information of a held/frozen embryo

  28. Case questions • Can you obtain family medical history as part of FMLA certification, if FMLA request is to care for a family member with a serious health condition? • Can you acquire genetic information through a genetic monitoring program that monitors biological effects of toxic substances in the workplace (biomonitoring)? • Can employers perform DNA tests on employees who engage in DNA testing for law enforcement, as a forensic lab, or for human remains identification? http://www.eeoc.gov/laws/types/genetic.cfm

  29. PCBs • Polychlorinated biphenyls (dielectric/coolant: capacitors, transformers, insulation, caulking) banned in 1979 • Leached into water supply, bioaccumulate in fish (and us), persist in environment • Estrogenic endocrine disruptor (brain development) • Males – undescended testicles, hypospadias, demasculinazation, sexual orientation, reduced fertility and sperm count, testicular cancer

  30. Used in caulk in schools in 1950s- 1978

  31. Phthalates • Di-ethylhexyl phthalate (DEHP) • Anti-androgen endocrine disruptor, inhibits testosterone • Ubiquitous – 2 million tons produced/year • Detected in 80% of Americans • Makes plastic soft and flexible • Food packaging: leaches faster with fattier foods, heated • Don’t have to list that it contains phthalates

  32. Reproductive and Developmental Toxin • Male genital development (testicular toxin) • Requires peak of testosterone in short critical developmental window Exposure  shortened anogenital distance  predictor of reduced sperm count & fertility • Infertility in males and females • Endocrine disruptor: Skeletal, cardiovascular, eye, neural tube defects, decreased intrauterine & postnatal growth, neurobehavior effects For health professionals: http://www.aoec.org/pehsu/documents/bpahealthcareproviderfactsheet10-2009.pdf For lay readers / parents: http://www.aoec.org/pehsu/documents/bpapatients%20factsheet10-2009.pdf

  33. Bisphenol A • 2,2-bis(4-hydroxyphenyl) propane • >8 billion pounds/year produced in US • Polycarbonate plastic and epoxy resins • Detectible in 93% of urine samples (2003 NHANES)

  34. Associated health effects… • Mimics estrogen & passes through placenta and detectable in fetal cord blood • Miscarriage & infertility • Decreased sperm counts • Early sexual maturation in females • Possibly contributes to PCOS • Possible: obesity, type 2 DM, breast and prostate cancer, neurobehavioral (ADHD) For health professionals: http://www.aoec.org/pehsu/documents/bpahealthcareproviderfactsheet10-2009.pdf For lay readers / parents: http://www.aoec.org/pehsu/documents/bpapatients%20factsheet10-2009.pdf

  35. Waste Water Treatment Plant Effluents CONTAIN: • Natural estrogens • Synthetic hormones and other pharmaceuticals • Pesticides • Toxic metals (mercury) • Phthalates • Bisphenol A

  36. Pregnancy-Induced Hypertension “Probably Linked” to PFOA Contamination 120(2) Feb 2012 • PFOA (perfluorooctanoic acid) used to manufacture Teflon • Found in blood of 98% of Americans • Residents near DuPont Teflon plant had over 5 times greater level than US average • Probable link with PIH in surrounding communities

  37. Possible developmental obesogens(shown in animals) • PFOA (teflon)  obesity as adult • PBDE (flame retardant)  Disrupts development of thyroid control of weight

  38. TransgenerationalObesogens • Exposure during development  permanent upregulation of lipid storage and maintenance • Exposed eggs  Changes in offspring of exposed fetus • Organotins (TBT) (marine coatings, wood preservative, PVC) (animals) • DDE/DDT (humans)

  39. Developmental Neurotoxins (Prenenatal exposures) • Chlorpyrifos (organophosphate) • Inhibits acetylcholinesterase alters synapse development • PBDE (flame retardants) • Phthalates • ADHD, autism spectrim disorder (esp boys) • Bisphenol A (abnormal behavior) The Lancet Neurology, Volume 13, Issue 3, Pages 330 - 338, March 2014

  40. Study Questions • Describe measures that a male or female worker can take to protect themselves from reproductive hazards at work. • Pick a legal topic (OSHA standards targeted at reproductive toxin, Pregnancy Act & Johnson Controls, FMLA, GINA) and describe how it applies to reproductive issues in the work place. (surveillance, employer-employee relationship, etc.) • Pick an example reproductive and an example developmental toxin (ok to use same for both, so long as both reproductive and non-reproductive developmental effects are demonstrated) found in consumer products (examples: phthalates or bisphenol A) and describe its sources, mechanism (anti-androgen etc.), reproductive health effects, and consumer choices (product choices or behaviors) to limit exposure • Describe some ways a female of child-bearing age can protect her future children by making good consumer choices before and during pregnancy

  41. PEHSU Program Disclaimer • This material was supported by the Association of Occupational and Environmental Clinics (AOEC) and funded under the cooperative agreement award number 1U61TS000118-03 from the Agency for Toxic Substances and Disease Registry (ATSDR). • Acknowledgement: The U.S. Environmental Protection Agency (EPA) supports the PEHSU by providing funds to ATSDR under Inter-Agency Agreement number DW-75-92301301-0. Neither EPA nor ATSDR endorse the purchase of any commercial products or services mentioned in PEHSU publications.

  42. Websites • DART: • http://www.toxnet.nlm.nih.gov • NIOSH: • http://www.cdc.gov/niosh/topics/repro/ • http://www.cdc.gov/niosh/topics/women/reproductive-health.html • OSHA • http://www.osha.gov/SLTC/reproductivehazards/ • EEOC • http://www.eeoc.gov/laws/types/pregnancy.cfm • Texas Workforce Commission • http://www.twc.state.tx.us/news/efte/pregnancy_rights.html • DOL • http://www.dol.gov/whd/regs/compliance/whdfs73.htm

  43. Articles • “Identifying Critical Windows of Exposure for Children's Health” Sherry G. Selevan, Carole A. Kimmel, and Pauline Mendola Environmental Health Perspectives Volume 108, Supplement 3, June 2000. • “Managing the Pregnant Employee” Donna Middaugh, Carla Hester. MedSurg Nursing, August, 2006. • Exposure to toxic environmental agents. Committee Opinion No. 575. American College of Obstetricians and Gynecologists. ObstetGynecol 2013;122:931-5. • Neurobehavioral Effects of developmental toxicity. Grandjean & Landrigan. The Lancet Neurology, Volume 13, Issue 3, Pages 330 - 338, March 2014 • NIOSH: The Effects of Workplace Hazards on Female Reproductive Health (http://www.cdc.gov/niosh/docs/99-104/) • NIOSH: The Effects of Workplace Hazards on Male Reproductive Health (http://www.cdc.gov/niosh/malrepro.html)

  44. Books “The Green Book” (Handbook of Pediatric Environmental Health, 2nd Edition, R. Etzel and S. Balk, eds. American Academy of Pediatrics, Nov 2003) • Chapter 2, pp 9-24: Developmental Toxicity: Special Considerations based on Age and Developmental Stage • Chapter 29, pp 443-458: Preconceptional and Prenatal Exposures Current Occupational & Environmental Medicine, 4th Ed., Joseph LaDou, 2007. • Chapter 25, pp 384-399: Female Reproductive Toxicology • Chapter 26, pp 400-412: Male Reproductive Toxicology

More Related