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Assessment Control of Hazards in the Workplace: Reproductive Risks

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Assessment Control of Hazards in the Workplace: Reproductive Risks

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    2. Objectives General understanding of occupational toxicology Hazard assessments (PBOELs)? Controls (OELs)? How OT, IH & OccHealth Teams collaborate Reproductive & developmental risk management program/tools

    16. Why such a concern?

    19. Moral, ethical and legal issues: collection of information poor experimental assays are limited (sperm output, fertility & measurement of hormone levels)? Not examined in routine autopsies Chemicals detected by semen analysis does not indicate toxicity Damage to the testis can cause recessive mutations in germ cells that may accumulate and go undetected for generations Unlike the ovaries, cell division in the testis is continuous Testicular cancer: not rare among young adult men (US) & rate ?

    21. Contraceptives: difficult to assess reproductive toxins in human females Targets: each has a specialized function under influence of the neuroendocrine system Ovaries are especially sensitive to insult; have dual functions; produce oocytes and secrete steroid hormones Oogenesis (egg production) starts before birth (first trimester)? Large number of dividing germ cells # viable eggs is limited: Birth- 2 million eggs Puberty- 30 to 40 thousand Post-maturation- 400 Damaged oocytes cannot be replaced causing sterility If chemical or radiation injury causes chromosomal damage, the damage lasts a lifetime

    22. Manifestations: growth retardation functional impairment structural malformations embryo lethality Factors critical to toxicity: Nature/inherent properties of toxin Level of exposure TIMING of exposure (organogenesis)? Numerous: radiation, infections, maternal imbalances, drugs and chemicals

    23. Damaged ovarian germ cells: mutations that can lead to developmental disorders or cancer Embryonal/fetal damage ? can produce various deformities that appear later rather than sooner Pregnancy stage determines the outcome Various organs have different periods of development and sensitivity

    24. Quality & production of breast milk Lipid soluble compounds accumulate in breast tissue and may be expressed in breast milk Nursing infants may be exposed to xenobiotics Methylene chloride, ETOH, heavy metals, KI, etc. Cannot tell if toxic to nursing infant Can only tell if it is present in breast milk

    27. Management Assure recommendations are implemented Cooperate with employee & professionals Communicate

    29. Resources

    30. Professional Judgment Methanol: Pregnant rats exposed to 20,000 ppm methanol in air during gestation experienced a significant increase in skeletal, urinary, and cardiovascular defects in the fetuses when compared to unexposed controls (Nelson et al, 1985). Ethidium bromide: This agent intercalates DNA strands and was mutagenic in a number of test systems (1,2). It is possible that nucleic acid alterations induced by ethidium make cells more susceptible to the effects of other cytotoxicants. Such an effect of ethidium has been demonstrated with respect to bleomycin (3), but not with respect to x ray (4). There are few studies on the potential embryotoxicity of ethidium. This agent is capable of arresting growth and development in early sea urchin embryos (5). Ethidium tested positive in the FETAX assay, a test system using toad embryos. The concentration of ethidium resulting in death of half the embryos was 0.05 mg/mL and the concentration resulting in malformation of half the embryos was 0.035 mg/mL (6). Neither the mutagenicity data nor the FETAX assay can be considered predictive of human response. We have not located any data on human reproductive or lactation effects of ethidium. Thalidomide: Human teratogen, but a weak teratogen in animals. Aspirin: Strong rodent teratogen, but no such effect on humans.

    36. Hazard & risk assessment programs Lack of SMEs (interpret information ?)? Workers taking unnecessary risks Particular susceptibility- repro organs & developmental Existing historical ‘taboo’ about early pregnancy Unreliable resources of information used for hazard ID No team approach to assessments & recommendations (integration of disciplines)? Lack of communication & understanding between groups Lack of clarity of responsibilities Resistance to make ‘decisions’ alone

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