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Pesticides: Pregnancy outcome and fertility
Markku Sallmén
Finnish Institute of Occupational Health
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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
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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?
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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
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Pesticides shown adverse effects on spermatogenesis
DBCP 2,4-D (2,4-dichlorophenoxy acetic acid) ethylene dibromide chlordecone carbaryl
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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
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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
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Pesticides and couples undergoing IVF treatment (Tielemans et al)
Reduced fertilization capacity
Improved implantation rate
Summary effect ?
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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
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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
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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
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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.
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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
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Pesticides and female fertility
Study Association
Fuortes et al 1997 + Curtis et al 1999 - Abell et al 2000 + Greenlee et al 2003 +
+ = reduced fertility
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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.
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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
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Female pesticide exposure and spontaneous abortion
Study
Association
Bell et al 2001
pesticides showed no strong association with fetal death
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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
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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
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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
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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
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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!