Pesticides: Pregnancy outcome and fertility

Markku Sallmén

Finnish Institute of Occupational Health

Pesticides

The most extensively used group of toxic chemicals

ca. 600 different active ingradients about 50,000 various formulations simultaneous exposure to different

chemicals typical pesticide formulations may contain

solvents

Pesticides

Comparison between studies difficult Different pesticides are used for different

purposes and in different areas Exposure levels vary considerably; the

highest exposures occur in developing countries in poorly controlled circumstances

What is the affected gender?

DBCP

The nematocide DBCP (dibromochloro-propane) is the most impressive occupational testicular toxin in men

Toxic to spermatogonia, thus causing azoospermia and oligospermia

only some affected workers had recovered from azoospermia to normal sperm count 7-11 years after exposure

Pesticides shown adverse effects on spermatogenesis

DBCP 2,4-D (2,4-dichlorophenoxy acetic acid) ethylene dibromide chlordecone carbaryl

Agent Orange

A mixture of 2,4-D and 2,4,5-T (2,4,5-trichlorophenoxy acetic acid

Association between paternal exposure and anencephaly and orofacial clefts

Lowered sperm quality 10-20 years after military service among American Vietnam veterans

Pesticides and male fecundability

Study Association de Cock et al 1994 + Larsen et al 1998 - Thonneau et al 1999 - Curtis et al 1999 - Petrelli et al 2001 + Sallmén et al 2003 (+)+ = reduced fecundability, (+) suggestive association

Pesticides and couples undergoing IVF treatment (Tielemans et al)

Reduced fertilization capacity

Improved implantation rate

Summary effect ?

Male pesticide exposure and spontaneous abortion

Savitz et al 1994 reviewed 14 studies

elevated RR in >1 study: YES RR > 1.5 YES Evidence from high

quality studies: NO

Male pesticide exposure and spontaneous abortion

Study Association (OR) Arbuckle et al 1999

farm couples, phenoxy herbicides

<20 weeks of gestation 1.1 0.6-1.9

<12 weeks of gestation 2.5 1.0-6.4

husband not using protective 5.0 0.7-36.2

equipment

Petrelli et al 2000 3.8 1.2-12.0 Crisostomo et al 2002 6.17 1.37-27.86

Male pesticide exposure and spontaneous abortion

Arbuckle et al 2001Ontario farm population

timing of exposure:

preconceptional early (12 weeks) abortions

postconceptional late (12-19 weeks) abortions

Male pesticide exposure and congenital malformations

García 1998, a review on occupational exposure and congenital malformations17 studies 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.

Male pesticide exposure and congenital malformations

Pesticide applicators in the Red River Valley of Minnesota (Garry et al, 1996, 2002)1996 a register-based study

- excess in birth defects

- seasonal pattern

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

Pesticides and female fertility

Study Association

Fuortes et al 1997 + Curtis et al 1999 - Abell et al 2000 + Greenlee et al 2003 +

+ = reduced fertility

DDT/DDE and female fertility:a two-generation study (Cohn et al 2003)

Maternal serum Fecundability of

concentration the daughter

increasing DDT reduced fec.

increasing DDE increased fec.

Female pesticide exposure and pregnancy outcome

Nurminen 1995, a review

Definition of exposure: ecological 5 studies place of residence 5 studies agricultural occupation 10 studies exposure at work 9 studies Conclusion: the epidemiologic evidence is

inconclusive as regards the risk of adverse pregnancy outcome

Female pesticide exposure and spontaneous abortion

Study

Association

Bell et al 2001

pesticides showed no strong association with fetal death

Female pesticide exposure and congenital malformations

Study Association (OR)

Medina-Carillo et al 2002 6.33 2.95-13.7

occupational exposure

Bell et al 2001 risk of malformation

increased within the

same square mile than the application

Parental pesticide exposure and congenital malformations

Kristensen et al 1997; a study among Norwegian farmers

Exposure to pesticides associated with:

spina bifida

hydrocephaly

limb reduction

cryptorchidism

hypospadias

Female DDT/DDE exposure and preterm birth and birth weight

StudyAssociation (OR)Longnecker et al 2001 concentration of DDE maternal serum DDE related to preterm birth in a dose- response manner

Torres-Arreola et al 2003 a weak association maternal serum DDE with preterm birth

Gladen at al 2003 no association with maternal milk DDE birth weight

Parental pesticide exposure and childhood cancer

There seems to be an association between father's work in agriculture and increased risk of brain tumors in their children

Kristensen et al (1996): use of pesticides was associated with cancer at early age

birth-month examination suggested paternal-mediated mechanism of pesticides

Pesticides conclusion

Several adverse outcomes in numerous studies

some studies negative the evidence suggest, that exposure is

associated with reproductive hazards => exposure should be restricted Problem: few harmful agents identified!