1. ISTC Research Symposium – September 9, 2009 Manoj K. Mohanty and Baojie Zhang Department of Mining and Mineral Resources Engineering Southern Illinois University at Carbondale

2.  Introduction  Objective  Project Methodology  Data Compilation  Data Analysis  Individual correlation coefficients (r)  Hypothesis testing  Multiple regression analysis  Monthly Average Concentrations  Conclusions  Recommendations  Acknowledgements 2

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4. 4 Illustration by Electronic Illustrators Group. http://medical-dictionary.thefreedictionary.com/Birth+Defects Causes of Birth Defects

5. 5 Past studies indicate: Illinois- among the highly nitrate contaminated states. Atrazine was detected in146 streams out of 149 sampled in the Midwestern states. Iowa study- Higher rates of intrauterine growth retardation (IUGR) with higher level of atrazine in drinking water Indiana study- Detrimental effects of disinfectant byproducts. Source: http://en.wikipedia.org/wiki/Grain_Belt US Corn-belt

6. To investigate the correlation of incidence rates of various negative reproductive outcomes with the concentration of key agrochemical based contaminants and disinfectant byproducts in drinking water used in Illinois. 6 Negative reproductive outcomes: Birth defects Adverse pregnancy outcomes Preterm births Drinking Water Contaminants: Nitrate Nitrite Atrazine Total trihalomethanes (TTHM) Five haloacetic acids (HAA5)

7. 7 1. Central Nervous System Defects4. Alimentary Tract Defects AnencephalusBiliary atresia EncephaloceleChoanal atresia HydrocephalusCleft lip MicrocephalusCleft palate Spina bifidaEsophageal atresia 2. Cardiovascular System DefectsHirschsprung disease Aortic valve stenosisPyloric stenosis Atrial septal defectRectal or large intestinal atresia/stenosis Coarctation of aorta5. Genitourinary System Defects Common truncusBladder exstrophy Ebstein anomalyHypospadias Endocardial cushion defectObstructive genitourinary defect Hypoplastic left heart syndromeRenal agenesis/hypoplasia Patent ductus arteriosusEpispadias Pulmonary artery anomalies6. Musculoskeletal Defects Pulmonary valve atresia and stenosisClub foot Tetralogy of FallotCongenital hip dislocation Transposition of great arteriesDiaphragmatic hernia Tricuspid valve atresia and stenosisGastroschisis Ventricular septal defectomphalocele 3. Respiratory System DefectsReduction deformity Lung agenesis/hypoplasia7. Chromosomal Defects Down syndrome Edward syndrome Patau syndrome

8. 1. Very low birth weight4. Perinatal deaths 2. Serious Congenital Infections5. Endocrine Metabolic or Immune Disorder ChlamydiaAdrenogenital syndrome Congenital syphilisGystic fibrosis Congenital tetanusImmune deficiency disease CytomegalovirusInborn errors of metabolism GonorrheaNeonatal hypothyroidism Group B streptococcus6. Fetal Alcohol Syndrome Hepatitis B virus7. Other Adverse Pregnancy Outcomes HerpsCerebral lipidoses ListeriosisChoriretinitis RubelaEndocardial fiberoelastosis SepsisIntrauterine growth retardation 3. Blood DisorderNeurofibromatosis CoagulationOcclusion of cerebral arteries Constitutional aplastic anemiaRetinopathy of prematurity Hereditary hemolytic anemiaStrabismus Leukomia 8

9. 1. Negative reproductive outcome (NRO) data for each county in Illinois for the five year period: 1998-2002. 2. Drinking-water contaminant data from community water supplies (CWS) for the same time period. 3. Correlation coefficients (r) between individual NRO and drinking water contaminants based on sample data and hypothesis testing. 4. Multiple regression analysis to investigate the correlations and their statistical significance by considering all five water contaminants simultaneously. 9

10. Birth Defects Incidence CasesRate Central Nervous System Defects512.0 Cardiovascular System Defects52125.1 Respiratory System Defects37.2 Alimentary Tract Defects716.8 Genitourinary System Defects1740.9 Musculoskeletal Defects1638.5 Chromosomal Defects49.6 Total104249.9 10 Example County: ADAMS

11. 11 Birth Defect Rates for Each County

12. 12 For all 102 counties in Illinois over the period of 1998-2002: Negative Reproductive Outcomes Number of Incidences Incidence Rate Range Birth Defects17,3790 to 485.6 Adverse Pregnancy38,7380 to 540.7 Preterm Birth89,097358.3 to1462.9

13. 13 County: ADAMS Nitrate Data CWS No. of Observation Observed Value (mg/L) Population Served Detection Limit (mg/L) Censored Value (mg/L) 1208.0571590.18.057 253.3608830.13.360 3196.34810660.16.348 4185.3182480.15.318 552.200450000.12.200 652.3026000.12.302 790.82018120.10.876 8206.16748900.16.167 952.704980.12.704 Total1062.64154,7562.643

14. 14 County: ADAMS Nitrite Data CWS No. of Observation Observed Value (mg/L) Population Served Detection Limit (mg/L) Censored Value (mg/L) 1200.001590.10.10 250.028830.10.12 3190.0010660.10.10 4180.002480.10.10 550.00450000.10.11 650.006000.10.10 790.0018120.10.10 8200.0048900.10.10 950.00980.10.10 Total1060.00054,7560.109

15. 15 Nitrite Data for Each County

16. Contaminants in Drinking Water Number of Measurements Observed Concentration Range Censored Concentration Range Observed Average IL Concentration Censored Average IL Concentration MCL Nitrate10,967 0 to 4.90 mg/L 0.043 to 4.91 mg/L 0.652 mg/L 0.709 mg/L 10 mg/L Nitrite9,909 0 to 0.190 mg/L 0.031 to 0.274 mg/L 0.003 mg/L 0.100 mg/L 1 mg/L Atrazine5,504 0 to 1.02 µg/L 0.156 to 1.185 µg/L 0.067 ug/L 0.343 µg/L 3 µg/L TTHM7,409 0.213 to 84.8 µg/L 0.947 to 84.9 µg/L 23.3 µg/L 23.2 µg/L 80 µg/L HAA54,407 0 to 64.9 µg/L 1.00 to 64.9 µg/L 10.4 µg/L 10.6 µg/L 60 µg/L 16

17.  Correlation Analysis where, SS xy = SS xx = SS yy = x i : contaminant concentration for each county y i : rate of negative reproductive outcome for each county  Hypothesis testing 17 where n represents the number of county water contaminant concentration values and r is the sample correlation coefficient

18. Nitrate (Observed data) Nitrate (Censored data) BD0.1630.164 APO0.0320.033 PB0.062 t-BD1.4761.491 t-APO0.2880.296 t-PB0.5530.555 Absolute t-critical; α=0.2;  =80 1.294 Significant CorrelationBD only 18 Sample correlation coefficient and hypothesis testing results BD: Birth defect; APO: Adverse Pregnancy Outcome; PB: Preterm Birth

19. NitrateNitriteAtrazineTTHMHAA5 Based on Observed Contaminant DataBDAPOPB BD PB Based on Censored Contaminant DataBD APO PB BD PB 19 Statistically Significant Correlations BD: Birth defect; APO: Adverse Pregnancy Outcome; PB: Preterm Birth

20. 20 Multiple Regression Analysis

21. No. of County Data Initial R 2 Final R 2 Final Critical F-value Significant main factors Significant factor interactions F-ratio BD Observed 820.2060.1321.901.85X3, X4,X4^2X1*X3,X1*X4, X4*X5 BD Censored 820.1630.0921.952.02X4,X4^2X1*X4, X4*X5 APO Observed 820.3580.2863.651.76X2,X4,X5,X3^2,X4 ^2 X1*X4,X2*X5,X4*X5 APO Censored 820.3580.2823.591.76X4, X5, X4^2X1*X2,X1*X4,X2*X3 X2*X5,X4*X5, PB Observed 820.1660.1101.971.92X5, X1^2X1*X2,X1*X4,X2*X5 PB Censored 820.2060.1182.582.02X2,X3,X5,X4^2NA X1: nitrate; X2: nitrite; X3: atrazine; X4: TTHM and X5:HAA5 21 BD: Birth defect; APO: Adverse Pregnancy Outcome; PB: Preterm Birth

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27.  As much as 16.3%, 35.8% and 20.6% of the variability in the rates of birth defects, adverse pregnancy outcomes and preterm births is explained by five contaminants (nitrate, nitrite, atrazine, TTHM and HAA5) in public drinking water supplies in IL.  TTHM, HAA5 and Nitrate- statistically significant for all three categories of negative reproductive outcomes.  Nitrite is significant for APO and PB only.  Atrazine is significant for all three categories of negative reproductive outcomes except the BD model based on censored data and PB model based on observed data. 27

28.  The monthly average concentrations of all three agro- chemical based contaminants are much higher in surface water based CWS.  Concentration of disinfectant byproducts are more in the GW based water supplies.  Atrazine concentration peaks in the months of May/June- agrees well with past studies.  The peak monthly average concentrations (118 μg/L in May and 98 μg/L in November) for TTHM are well above the corresponding MCL of 80 μg/L.  The peak concentrations of HAA5 of 75 μg/L in May and 100 μg/L in November for HAA5 are well above the corresponding MCL of 60μg/L. 28

29.  Surface water based CWS and Ground water based CWS may be separately examined.  For developing meaningful correlations for some of the individual BD and APO, a data set covering a much longer time period (maybe 10 to 20 years) will be required.  A much more comprehensive study using controlled experiments in future should include all known factors contributing to various negative reproductive outcomes to develop predictive models for each or at least some of them. 29

30.  Illinois Sustainable Technology Center  United States Geological Survey  Illinois Environmental Protection Agency  Illinois Department of Public Health  Indiana University Medical Research Center 30

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34. NitrateNitriteAtrazineTTHMHAA5 Statistically Significant Contaminant Based on Observed Data HAA5 TTHM HAA5 Atrazine TTHM Atrazine Statistically Significant Contaminant Based on Censored DataTTHMHAA5 TTHM HAA5 Atrazine Nitrate TTHM Atrazine Nitrite 34 Correlation among the exploratory variables

35.  Occurrence of a specific adverse outcome is assumed to be a rare event, therefore such occurrences are assumed to follow a Poisson distribution. Where there are a large number of birth defect cases, the confidence interval is narrow, indicating that the rate is stable. Where there are few birth defect cases, the confidence interval becomes very wide, indicating that the rate is not very stable. 35 - where Y is the observed number of events, Yl and Yu are lower and upper confidence limits for Y respectively, c²n,a is the chi-square quantile for upper tail probability a on n degrees of freedom.

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