1. Pesticides: Pregnancy outcome and fertility Markku Sallmén Finnish Institute of Occupational Health

2. Pesticides n The most extensively used group of toxic chemicals n ca. 600 different active ingradients n about 50,000 various formulations n simultaneous exposure to different chemicals typical n pesticide formulations may contain solvents

3. Pesticides n Comparison between studies difficult n Different pesticides are used for different purposes and in different areas n Exposure levels vary considerably; the highest exposures occur in developing countries in poorly controlled circumstances n What is the affected gender?

4. DBCP n The nematocide DBCP (dibromochloro- propane) is the most impressive occupational testicular toxin in men n Toxic to spermatogonia, thus causing azoospermia and oligospermia n only some affected workers had recovered from azoospermia to normal sperm count 7-11 years after exposure

5. Pesticides shown adverse effects on spermatogenesis n DBCP n 2,4-D (2,4-dichlorophenoxy acetic acid) n ethylene dibromide n chlordecone n carbaryl

6. Agent Orange n A mixture of 2,4-D and 2,4,5-T (2,4,5- trichlorophenoxy acetic acid n Association between paternal exposure and anencephaly and orofacial clefts n Lowered sperm quality 10-20 years after military service among American Vietnam veterans

7. Pesticides and male fecundability n StudyAssociation n de Cock et al 1994+ n Larsen et al 1998- n Thonneau et al 1999- n Curtis et al 1999- n Petrelli et al 2001+ n Sallmén et al 2003(+) + = reduced fecundability, (+) suggestive association

8. Pesticides and couples undergoing IVF treatment (Tielemans et al) n Reduced fertilization capacity n Improved implantation rate n Summary effect ?

9. Male pesticide exposure and spontaneous abortion Savitz et al 1994 reviewed 14 studies n elevated RR in >1 study: YES n RR > 1.5YES n Evidence from high quality studies:NO

10. Male pesticide exposure and spontaneous abortion Study Association (OR) n Arbuckle et al 1999 farm couples, phenoxy herbicides <20 weeks of gestation1.10.6-1.9 <12 weeks of gestation 2.51.0-6.4 husband not using protective 5.00.7-36.2 equipment n Petrelli et al 20003.81.2-12.0 n Crisostomo et al 20026.17 1.37-27.86

11. Male pesticide exposure and spontaneous abortion n Arbuckle et al 2001 Ontario farm population timing of exposure: preconceptionalearly (12 weeks) abortions postconceptionallate (12-19 weeks) abortions

12. Male pesticide exposure and congenital malformations García 1998, a review on occupational exposure and congenital malformations n 17 studies n 4 studies showed an association Conclusion: Inadequate evidence for either establishing a relationship between pesticides exposure in humans and birth defects or for rejecting it.

13. Male pesticide exposure and congenital malformations Pesticide applicators in the Red River Valley of Minnesota (Garry et al, 1996, 2002) n 1996 a register-based study - excess in birth defects - seasonal pattern n 2002 a cross-sectional interview study - rate of birth defects 7.6% (spring) vs. 3.7% other season - herbicides: risk of birth defects - fungisides: determination of sex of the children

14. Pesticides and female fertility n StudyAssociation n Fuortes et al 1997+ n Curtis et al 1999- n Abell et al 2000+ n Greenlee et al 2003+ + = reduced fertility

15. DDT/DDE and female fertility: a two-generation study (Cohn et al 2003) n Maternal serumFecundability of concentrationthe daughter n increasing DDT reduced fec. n increasing DDEincreased fec.

16. Female pesticide exposure and pregnancy outcome Nurminen 1995, a review Definition of exposure: n ecological 5 studies n place of residence 5 studies n agricultural occupation10 studies n exposure at work 9 studies n Conclusion: the epidemiologic evidence is inconclusive as regards the risk of adverse pregnancy outcome

17. Female pesticide exposure and spontaneous abortion StudyAssociation Bell et al 2001pesticides showed no strong association with fetal death

18. Female pesticide exposure and congenital malformations StudyAssociation (OR) Medina-Carillo et al 20026.33 2.95-13.7 occupational exposure Bell et al 2001risk of malformation increased within the same square mile than the application

19. Parental pesticide exposure and congenital malformations Kristensen et al 1997; a study among Norwegian farmers n Exposure to pesticides associated with: spina bifida hydrocephaly limb reduction cryptorchidism hypospadias

20. Female DDT/DDE exposure and preterm birth and birth weight StudyAssociation (OR) Longnecker et al 2001concentration of DDE maternal serum DDErelated to preterm birth in a dose- response manner Torres-Arreola et al 2003a weak association maternal serum DDEwith preterm birth Gladen at al 2003no association with maternal milk DDEbirth weight

21. Parental pesticide exposure and childhood cancer n There seems to be an association between father's work in agriculture and increased risk of brain tumors in their children n Kristensen et al (1996): use of pesticides was associated with cancer at early age birth-month examination suggested paternal- mediated mechanism of pesticides

22. Pesticides conclusion n Several adverse outcomes in numerous studies n some studies negative n the evidence suggest, that exposure is associated with reproductive hazards n => exposure should be restricted n Problem: few harmful agents identified!