1. Solvents: pregnancy outcome and fertility Marja-Liisa Lindbohm Finnish Institute of Occupational Health

2. Organic solvents one of the most important occupational reproductive hazards: one of the most important occupational reproductive hazards:  widely used in various fields of industry  volatile liquids  absorbed via inhalation and through the skin  most solvents traverse the placenta

3. Reproductive effects of solvents teratogenic, embryotoxic and behavioral effects in animal tests on mammals teratogenic, embryotoxic and behavioral effects in animal tests on mammals in several human studies exposure related to in several human studies exposure related to  adverse pregnancy outcome and reduced fertility in some studies exposure related also to in some studies exposure related also to  menstrual disorders and reduced hormone levels  reduced semen quality  pregnancy-induced hypertension  neurobehavioral performance  childhood cancer

4. Industries / individual solvents related to reduced fertility or adverse pregnancy outcome Dry cleaning / tetrachloroethylene Dry cleaning / tetrachloroethylene Shoe and leather industry / aliphatic hydrocarbons, toluene, hexane Shoe and leather industry / aliphatic hydrocarbons, toluene, hexane Semiconductor industry / ethylene glycol ethers Semiconductor industry / ethylene glycol ethers Laboratory work / toluene, xylene, chloroform Laboratory work / toluene, xylene, chloroform

5. Maternal exposure to tetrachloroethylene in dry cleaning and spontaneous abortion

6. Spontaneous abortion, subfertility and maternal exposure to ethylene glycol ethers in semiconductor industry (Correa et al. 1996)

7. Results of studies among women working in the shoe and leather industry indications of an increased risk of perinatal death, stillbirth, and oral clefts in children of shoe and leather workers (likely exposed to solvents) indications of an increased risk of perinatal death, stillbirth, and oral clefts in children of shoe and leather workers (likely exposed to solvents) increased risk of spontaneous abortion and decreased fertility among shoe workers exposed to solvents (aliphatic hydrocarbons, toluene, hexane, acetone) increased risk of spontaneous abortion and decreased fertility among shoe workers exposed to solvents (aliphatic hydrocarbons, toluene, hexane, acetone)

8. Cumulative percentage of pregnancies by maternal exposure to solvents (Sallmén et al 1995)

9. Maternal exposure to solvents and birth defects McMartin et al. 1998: McMartin et al. 1998:  meta-analysis of five studies (n=7036)  summary OR=1.64 (95% CI 1.16 - 2.30) Solvent exposure linked with Solvent exposure linked with  central nervous system defects, oral clefts, gastroschisis, ventricular septal defects, urinary tract defects

10. Conclusions: Effects of solvent exposure on the reproductive health of women High exposure to solvents increases the risk of spontaneous abortion and decreases fertility High exposure to solvents increases the risk of spontaneous abortion and decreases fertility The findings on birth defects less conclusive, but suggesting adverse effects The findings on birth defects less conclusive, but suggesting adverse effects Particular solvents associated with adverse outcome: ethylene glycol ethers, tetrachloro- ethylene, toluene Particular solvents associated with adverse outcome: ethylene glycol ethers, tetrachloro- ethylene, toluene

11. Exposure to solvents and semen quality or hormone levels 2-bromopropane: reduced sperm count 2-bromopropane: reduced sperm count Ethylene glycol ethers: reduced sperm count Ethylene glycol ethers: reduced sperm count Styrene and acetone: sperm anomalies Styrene and acetone: sperm anomalies Toluene: decrease of gonadotropin hormone levels Toluene: decrease of gonadotropin hormone levels Trichloroethylene: hyperzoospermia Trichloroethylene: hyperzoospermia Solvents: low active sperm count and decreased implantation rate Solvents: low active sperm count and decreased implantation rate

12. Cumulative percentage of pregnancies by paternal exposure to solvents (Sallmén et al. 1998)

13. Conclusions: Effects of solvent exposure on the reproductive health of men Ethylene glycol ethers harmful for male reproductive system Ethylene glycol ethers harmful for male reproductive system Carbon disulfide related to decreased libido and potency in men Carbon disulfide related to decreased libido and potency in men No clear association between solvent exposure and decreased fertility No clear association between solvent exposure and decreased fertility Evidence on the effects of paternal exposure on pregnancy outcome inconclusive, although suggestive associations noted Evidence on the effects of paternal exposure on pregnancy outcome inconclusive, although suggestive associations noted

14. Hazard assessment Exposure may be high for example in spray painting, shoe making, degreasing, printing and dry cleaning Exposure may be high for example in spray painting, shoe making, degreasing, printing and dry cleaning Assessment of solvent exposure with industrial hygienic measurements or biological monitoring Assessment of solvent exposure with industrial hygienic measurements or biological monitoring In some countries the guidelines recommend that solvent exposure should not exceed 10% of the threshold limit value during pregnancy In some countries the guidelines recommend that solvent exposure should not exceed 10% of the threshold limit value during pregnancy

15. References on solvent exposure and reproductive health McMartin KI, Chu M, Kopecky E, Einarson TR, Koren G. Pregnancy outcome following maternal organic solvent exposure: a meta-analysis of epidemiologic studies. Am J Ind Med 1998;34:288-292. McMartin KI, Chu M, Kopecky E, Einarson TR, Koren G. Pregnancy outcome following maternal organic solvent exposure: a meta-analysis of epidemiologic studies. Am J Ind Med 1998;34:288-292. Tas S, Lauwerys R, Lison D. Occupational hazards for the male reproductive system. Crit Rev Toxicol 1996;26:261-307. Tas S, Lauwerys R, Lison D. Occupational hazards for the male reproductive system. Crit Rev Toxicol 1996;26:261-307. Lindbohm M-L. Effects of parental exposure to solvents on pregnancy outcome. J Occup Environ Med 1995;37:908-914. Lindbohm M-L. Effects of parental exposure to solvents on pregnancy outcome. J Occup Environ Med 1995;37:908-914.