Reproductive Toxicity Reproductive Toxicity

Pesticide Health Effects Medical Education Database (PHEMED) 2010

Reproductive

Menstrual CyclesMenstrual Cycles

Birth defectsBirth defects

Time to pregnancyTime to pregnancy

Small for Age at BirthSmall for Age at Birth

MiscarriagesMiscarriages

Women using pesticides have 1.5 x increased Women using pesticides have 1.5 x increased odds of *odds of *

Longer cyclesLonger cycles

Missing a periodMissing a period

Hormonally active pesticides increase odds of Hormonally active pesticides increase odds of missed periods, long cycles, bleeding mid cycle.missed periods, long cycles, bleeding mid cycle.

LindaneLindane

AtrazineAtrazine

Mancozeb or ManebMancozeb or Maneb

Source: Farr SL, Cooper GS, Cai J, Savitz DA, Sandler DP. Pesticide use and menstrual cycle characteristics among premenopausal women in the Agricultural Health Study. (2004). American Journal of Epidemiology, 160(12):1194-204.

Menstrual Cycle Changes

Birth Defects:Study Design Issues

Indirect exposure measurements withoutIndirect exposure measurements withoutbiomarkers:biomarkers:

Work recordsWork records

Places of residencePlaces of residence

DatabasesDatabases

QuestionnairesQuestionnaires

Only cases that survive birth are counted Only cases that survive birth are counted (miscarried fetuses? )(miscarried fetuses? )

Birth Defects

Consistent findings withConsistent findings with Limb reductions - Uro-genital defectsLimb reductions - Uro-genital defects

Central nervous systemCentral nervous system

Cleft palates/lips: marginal significant w/ maternal Cleft palates/lips: marginal significant w/ maternal exposure exposure

Eye – heart defectsEye – heart defects

Not definitive until better exposure analysis with Not definitive until better exposure analysis with the US Children’s Health Studythe US Children’s Health Study

Source: Sanborn M, Cole D, Kerr K, Vakil C, Sanin LH, Bassil K. Pesticides Literature Review. Ontario College of Family Physicians. Toronto 2004.

Time to Pregnancy

Studies Studies suggestsuggest that occupational that occupational exposure increase time needed to become exposure increase time needed to become pregnantpregnant20% - in women engaged in pesticide 20% - in women engaged in pesticide activities + husband also engaged in same activities + husband also engaged in same – but – but impreciseimprecise due to small numbers due to small numbers Associated with dicamba, glyphosate, 2,4-Associated with dicamba, glyphosate, 2,4-D, thiocarbamates, OP’s although not D, thiocarbamates, OP’s although not statistically significant statistically significant

Source: Curtis KM, Savitz DA, Weinberg CR, Arbuckle TE. The effect of pesticide exposure on time to pregnancy. Epidemiology. 1999 Mar;10(2):112-7.

Effect of Pesticide Exposure on Male Fertility

Decreases in sperm countDecreases in sperm count

Diminished percent of viable spermDiminished percent of viable sperm

Changes in sperm morphologyChanges in sperm morphology

Hormonal changes Hormonal changes – Higher estradiol and lower LH levelsHigher estradiol and lower LH levels– Lower testosteroneLower testosterone

Sperm aneuploidySperm aneuploidy

Associations to specific pesticidesAssociations to specific pesticides– Fumigants : DBCP (banned soil fumigant) EDB wood fumigantFumigants : DBCP (banned soil fumigant) EDB wood fumigant

– Insecticides: Insecticides: organosphoshates, pyrethroids (organosphoshates, pyrethroids (fenverlate )fenverlate )

– Herbicides: Herbicides: 2,4-D, 2,4-D, alochlor, metochlor, alochlor, metochlor, atrazineatrazine

Sources: Jurewicz J. IJOMEH 2009 ,Carlsen E. BMJ 1992 and Ratcliffe JM BMJ 1987 and Recio R et al. EHP 2001 and Meeker JD. EHP 2004 and Lifeng T Contraception 2006 and Sean S. EHP 2003

Probable linkProbable linkFetal and maternal blood Fetal and maternal blood samples for OP by-products samples for OP by-products and newborn lengthsand newborn lengthsChlorpyrifos and diazinon Chlorpyrifos and diazinon [by-[by-products measured in fetal and maternal products measured in fetal and maternal

blood]blood] associated to lower birth associated to lower birth weight and length*weight and length*

Small for Age at Birth

* Whyatt RM et al. Biomarkers in assessing residential insecticide exposures during pregnancy and effects on fetal growth. Tox Applied Pharm 206 (2): 246-254 AUG 7, 2005

Miscarriages

Studies suggest an association Studies suggest an association Critical exposure windows and certain Critical exposure windows and certain pesticidespesticides

One - four months before conception One - four months before conception Non use of PPE increased risk 5 fold in one studyNon use of PPE increased risk 5 fold in one study

Study Method ProblemsStudy Method ProblemsNo data on miscarriage rates in general populationNo data on miscarriage rates in general populationHigh % go undetectedHigh % go undetected?? Role of other farm toxins (animal viruses, heavy ?? Role of other farm toxins (animal viruses, heavy metals) largely unknown in studiesmetals) largely unknown in studies

Sources: Arbuckle et al 1999 and 2001; Garry VF et al 2002