Carcinogenic Health Risk Assessment Of Nitrosamines In Drinking Water And Effects Of Their Exposures During Pregnancy On Birth Outcomes

Nitrosamines,the emerging drinking water disinfection by-products（DBPs）with high carcinogenicity and genotoxicity,are produced during the process of disinfection of drinking water.Recently,the different species and levels of nitrosamines have been detected in drinking water systems across different countries and regions.However,there is lacking data on the human carcinogenic risk of exposure to drinking water nitrosamines.Moreover,experimental studies have shown that nitrosamines have the the reproductive and developmental toxicity and maternal exposure of nitrosamines can be circulated into the fetus through the placenta.However,there is no epidemiological study on the effects of maternal exposure to drinking water nitrosamines during pregnancy and fetal growth.Therefore,we conducted a yearly monitoring campaign in a water supply system in Xiaogan City,in which influent water,treated water and tap waters from 6 sampling sites were collected.The spatial and temporal variability of nitrosamines in drinking water were evaluated,and the carcinogenic risk caused by exposure to dinking water nitrosamines for the local population was assessed.Furthermore,we calculated the maternal exposure of drinking water nitrosamines during pregnancy by linking the monitoring data with maternal residential address.The associations between maternal drinking water nitrosamine exposures during pregnancy and birth outcomes were analyzed.The study was divided into two parts as follow.Part one Human carcinogenic risk assessment of exposure to nitrosamines in drinking waterObjective:Our study aimed to investigate the spatial and temporal variability of nitrosamines in a drinking water system and further to conduct a carcinogenic health risk assessment based on the monitoring data.Methods:Three types of water samples,including influent water,treated water and tap waters from 6 sampling sites,were collected monthly from January 2016 to December 2016 in a drinking water system in Xiaogan City.Nine nitrosamines were measured by solid phase extraction-liquid chromatograph-mass spectrometer technology.The temporal and spatial variability of drinking water nitrosamines were assessed.Based on the monitoring data of drinking water nitrosamines,carcinogenic risk assessment for children and adults were estimated using the method recommended by United States Environmental Protection Agency（USEPA）.Results:N-nitrosodimethylamine（NDMA）,N-nitrosodiethylamine（NDEA）and N-nitrosopiperidine（NPIP）were all detected>50%in each type of samples,while the others were detected≤25%or not detected.NDMA was dominant in the water samples with average concentrations ranging from 2.5 to 67.4 ng/L.The occurrence of nitrosamines in the drinking water system varied monthly,and statistically significant seasonal differences were observed in tap water（P<0.05）.There were decreasing mean NDMA,NDEA and NPIP concentrations from influent water to treated water to tap water,but no statistically significant difference was observed（P>0.05）.The average total lifetime cancer risk for the humans exposed to drinking water NDMA,NDEA and NPIP via ingestion was 4.83×10^-5,exceeding the negligible risk level(1×10^-6)proposed by the USEPA.Exposure to nitrosamines in drinking water posed a higher cancer risk for children than for adults,and children aged 0.75 to 1 years suffered the highest cancer risk.Conclusions:The occurrence of nitrosamines in drinking water varied temporally but not spatially.Exposure to drinking water nitrosamines may pose a carcinogenic risk to human health,especially to children.Part two Effects of gestational exposure to drinking water nitrosamines on birth outcomesObjective:To explore the associations between maternal trimester-specific or entire pregnancy exposure to nitrosamines in drinking water and indices of fetal growth[birth weight（BTW）,low birth weight（LBW）,small for gestational age（SGA）and preterm delivery（PTD）].Methods:We included 2457 mother-infant pairs who went to a hospital in Xiaogan city for delivery and lived in the study drinking water system during the entire pregnancy from October 2015 to December 2016.The basic information for mothers and birth outcomes for infants were obtained from the delivery records in the hospital.Maternal trimester-specific and entire pregnancy exposure of drinking water nitrosamines were evaluated based on maternal residential address and monthly monitoring data from six tap water sampling sites located in the water supply system.We estimated the associations of maternal exposure to nitrosamines in drinking water with BTW,LBW,SGA and PTD by multivariable linear and logistic regression models.Results:The maternal exposure levels of drinking water NDMA was the highest during the pregnancy,followed by NDEA and NPIP.Maternal average exposure of the sum of the three main nitrosamines（NDMA,NDEA and NPIP）in the first,second and third trimester and the entire pregnancy was 29.5 ng/L,19.7 ng/L,24.6 ng/L and 26.1ng/L,respectively.The results of multivariate linear regression models indicated that elevated maternal NDMA exposure during the entire pregnancy was associated with lower infant BTW（P for trend=0.07）,and the mean infant BTW in the third tertile of maternal exposure decreased 35.1 g（95%CI:-72.9,2.7）compared with the first tertile of exposure.The results of multivariate logistic regression models indicated that elevated maternal exposure of NDEA in the second trimester was associated with increased risk of SGA（P for trend=0.01）,and the risk of SGA for the third tertile of maternal exposure is 1.86（95%CI:1.11,3.11）times than the first tertile of exposure.Moreover,increased risks of PTD were estimated for maternal NDMA exposure in the second trimester and NPIP exposure during the entire pregnancy（both P for trend<0.05）.Conclusions:Maternal exposure to drinking water nitrosamines during pregnancy was associated with decreased BTW and increased risks of SGA and PTD.