2. Objectives General understanding of occupational toxicology
Hazard assessments (PBOELs)?
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
Damaged oocytes cannot be replaced causing sterility
If chemical or radiation injury causes chromosomal damage, the damage lasts a lifetime
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
Assure recommendations are implemented
Cooperate with employee & professionals
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).
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.
Human teratogen, but a weak teratogen in animals.
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