Exposure to Manganese from Agricultural Pesticide Use and Neurodevelopment in Young Children

Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, this dissertation shows that agricultural use of fungicides that contain manganese (Mn) results in higher levels of Mn in children's homes and teeth, and that higher Mn levels in children's teeth are associated with a modest deficit in neurodevelopment at 6-months of age. In Chapter 2, predictors of Mn concentrations and loadings in house dust samples are evaluated. The fungicides maneb and mancozeb are approximately 21% Mn by weight and more than 150,000 kg are applied each year to crops in the Salinas Valley, California. It is not clear whether agricultural use of these fungicides increases Mn levels in homes. In this study, predictors of Mn levels in house dust samples are evaluated. House dust samples were collected from 378 residences enrolled in the CHAMACOS study with a second sample collected nine months later from 90 residences. House dust samples were analyzed for Mn using inductively coupled plasma optical emission spectroscopy. Information from interviews, home inspections, and pesticide use reporting data was used to identify potential predictors of Mn dust concentrations and loadings. Linear mixed-effects models were used to identify significant predictors. Mn was detectable in dust samples from all homes. The median Mn concentration was 171 µg/g and median Mn loading was 1,908 µg/m2 at first visit. In multivariable models, Mn dust concentrations and loadings increased with the number of farmworkers in the home and the amount of agricultural Mn fungicides applied within three kilometers of the residence. Dust concentrations and loadings were higher in residences located on Antioch Loam soil than other soil types, in homes with poor or average compared to excellent housekeeping practices, and residences located in the southern Salinas Valley compared those located in the town of Salinas or the northern part of the Salinas Valley. In summary, agricultural use of Mn containing fungicides were found to contribute to Mn dust concentrations and loadings in nearby residences and farmworker homes./nChapter 3 presents an analysis that identifies determinants of Mn in prenatal dentin from children's shed teeth. Mn is an essential nutrient, but over-exposure can be neurotoxic. Over 800,000 kilograms of Mn-containing fungicides are applied each year in California. Manganese levels in teeth are a promising biomarker of perinatal exposure. Participants in this analysis included 207 children enrolled in the CHAMACOS study, a longitudinal birth cohort study in an agricultural area of California. Mn was measured in teeth using laser-ablation-inductively coupled plasma-mass spectrometry. The purpose of this analysis was to determine environmental and lifestyle factors related to prenatal Mn levels in shed teeth. Storage of farmworkers' shoes in the home, maternal farm work, agricultural use of Mn-containing fungicides within 3 km of the residence, residence built on Antioch Loam soil and Mn dust loading (µg/m2 of floor area) during pregnancy were associated with higher Mn levels in prenatal dentin (p<0.05). Maternal smoking during pregnancy was inversely related to Mn levels in prenatal dentin (p<0.01). Multivariable regression models explained 22 - 29% of the variability of Mn in prenatal dentin. These results suggest that Mn measured in prenatal dentin provides retrospective and time specific levels of exposure to the fetus resulting from environmental and occupational sources./nChapter 4 evaluates the association between Mn in prenatal and postnatal dentin of children's shed teeth and early neurodevelopment. Previous studies have observed associations between Mn exposure and children's neurodevelopment, primarily using concurrent exposure measurements in blood or hair. Prenatal and postnatal Mn exposures have not been evaluated together in a prospective study of neurodevelopment in young children. Mn levels in prenatal and postnatal dentin were measured from children's shed teeth. The relationship between prenatal and postnatal exposure and children's performance at 6, 12 and 24-months of age on the Bayley Scales of Infant Development mental and psychomotor development indices was examined. The possibility of an inverted U-shaped association with neurodevelopment was explored since Mn is an essential nutrient. Potential interactions between Mn exposure and blood lead concentrations were also evaluated as well as effect modification by maternal iron status during pregnancy. An inverse association between postnatal Mn levels in dentin and psychomotor development at 6-months of age was observed with a modest decrease in psychomotor development scores, which followed an inverse U-shape, with the strongest effect observed when comparing the highest tertile of Mn levels in teeth to the middle tertile of Mn levels in teeth (-4.6 points; 95% Confidence Interval: -8.0, -1.3). Among children whose mothers' were iron deficient during pregnancy, prenatal Mn levels in dentin were associated with both mental and psychomotor development at 6-months. No interactions with prenatal or postnatal blood lead concentrations were observed in this cohort. In conclusion, a modest decrease in psychomotor development at 6-months of age was associated with postnatal Mn levels in dentin from a mean score of 96 for the middle tertile compared to 94 at the highest tertile. Iron status during pregnancy appeared to be a potentially important effect modifier of prenatal Mn exposure and neurodevelopment at 6-months of age.

Advisor: Eskenazi, Brenda
Jerrett, Michael