820-R-10-018 Fluoride: Dose-Response Analysis For Non-cancer Effects Dental Fluorosis: Evaluations of Key Studies Health and Ecological Criteria Division Office of Water January, 2008 U.S. Environmental Protection Agency Washington, D.C. TABLE OF CONTENTS ACKNOWLEDGMENTS ............................................................................................................. 3 INTRODUCTION ......................................................................................................................... 4 STUDY SUMMARIES .................................................................................................................. 5 2 January, 2008 ACKNOWLEDGMENTS This document was prepared by Oak Ridge National Laboratory, Oak Ridge, Tennessee, under work assignment 2006-014, under the U.S. EPA IAG Number DW-89-9220971. The Principal EPA Scientist is Joyce M. Donohue, Ph.D., Health and Ecological Criteria Division, Office of Science and Technology, Office of Water, U.S. Environmental Protection Agency, Washington, DC. The summaries included in this report were prepared by C. Wood, S. Milanez, D. Glass, S. Garcia, S. Goldhaber, and V. Dobozy. Summary reviewers included J.M. Donohue and T. Duke of the Health and Ecological Criteria Division, Office of Science and Technology, Office of Water, U.S. EPA; and D. Glass, D. Opresko and A. Watson of ORNL. The Oak Ridge National Laboratory is managed and operated by UT-Battelle, LLC., for the U.S. Department of Energy under Contract No. DE-AC05-00OR22725. 3 January, 2008 INTRODUCTION Prior to initiating the dose-response analysis for severe dental fluorosis, the Office of Water (OW) critically evaluated the studies that had been cited and utilized by the National Research Council (NRC, 2006) in their report Fluoride in Drinking Water: A Scientific Review of EPA’s Standards. Additional studies identified in the OW initial literature search (2006) were also evaluated. Critical information fields examined and summarized include endpoint studied, type of study and population studied, exposure period and assessment, characterization of study groups, analytical methods and study design, parameters monitored, statistical methods employed, results (including critical tables and figures) authors’ conclusions, critical references and definitions, profiler’s appraisal, and critical review of the profiler’s assessment. This document is a compilation of the study evaluations arranged alphabetically by the name of the lead author. Dental fluorosis studies identified and added to the dose-response analysis for the non-cancer effects document after its external peer review were not evaluated in this fashion. 4 January, 2008 STUDY SUMMARIES Dental Fluorosis 5 January, 2008 Acharya, S. 2005. Dental caries, its surface susceptibility and dental fluorosis in South India. International Dental Journal, 55(6): 359-64. ENDPOINT STUDIED: Dental fluorosis and dental caries TYPE OF STUDY: Cross-sectional survey POPULATION STUDIED: India/Karnataka State (Deccan Peninsula). 544 schoolchildren (301 males and 243 females) aged 12-15 years old from five different villages (Nallur, Naganur, Doddabathi, Kundawada and Holesirigere) within Karnataka State (Davangere District) were studied. All children were native to the region. CONTROL POPULATION: none EXPOSURE PERIOD: Schoolchildren that were continuous residents of the studied villages since birth and ranged in age from 12-15 years. EXPOSURE GROUPS: The number of children examined in each village and the fluoride concentration identified in the water supply for the village are provided in the table below. All children were in approximately the same socioeconomic status and sorghum was the main staple food item. Water was obtained in the villages from bore wells and was either pumped to a centralized storage tank where residents obtained water through a tap on the tank or through the Accelerated Rural Water Supply which distributed the bore well water to the consumers. The wells were approximately 15-18 years old. Name of Village No. of children examined Fluoride conc. of water Nallur 163 0.43 ppm Naganur 49 0.72 ppm Kundawada 96 1.10 ppm Doddabathi 81 1.22 ppm Holesirigere 155 3.41 ppm EXPOSURE Only drinking water was analyzed for fluoride content in this study. The fluoride content in ASSESSMENT: food and beverages (i.e. tea) was not measured. Information regarding food habits was asked of the participants but data characterizing consumption or fluoride concentrations were not included for the assessment. ANALYTICAL METHODS: Information about the age of the wells (15-18 years old) and the fact that the water supply had been from a constant source was obtained from the local and village councils and the Public Health Engineering Dept. of Davangere District. The analytical method used to measure fluoride in the wells was the ion selective electrode method developed by the Orion Research Incorporated Laboratories Products Group, USA. The model used was (94.09, 96.09) electrode 720A from Orion Instruments. Information about other parameters measured in the water was not included in the paper. STUDY DESIGN 544 schoolchildren (301 males and 243 females) aged 12-15 years old from five different villages (Nallur, Naganur, Doddabathi, Kundawada and Holesirigere) within Karnataka State (Davangere District) were studied. The age distribution was 170 (31.2%) in the 12-13 year old group, 201 (36.9%) in the 13-14 year old group and 173 (31.8%) in the 14-15 year old group. Dental examinations were performed one time on the children in their schools. Children were examined under natural light while sitting on a chair or stool. Children were assessed for the presence and degree of fluorosis and the evidence of caries. PARAMETERS The author of this paper (S. Acharya) was the dental examiner for the study and was trained in MONITORED: the WHO criteria for assessing fluorosis and caries prior to the start of the study. Dean’s 6 January, 2008 criteria (1942) were used to assess fluorosis, and the Community Fluorosis Index (CFI) (Dean 1942) was calculated to assess the public health significance of fluorosis from each village. Dental caries were assessed using the DMFS index (Klein et al. 1938). The type of carious lesion present was also recorded: pit and fissure lesions or smooth surface lesions. Occlusal, lingual and buccal pit and fissure lesions were classified under pit and fissure lesions. Proximal lesions and lesions on buccal, lingual and occlusal and incisal surfaces other than pit and fissures were classified under smooth surface lesions. STATISTICAL METHODS: All data analysis was done on Minitab Statistical Software (Version 13). The Karl Pearson coefficient for correlation and simple regression analysis was used to measure the correlation between fluoride concentration in the drinking water and dental caries. The F test was used for estimation of statistical significance and statistical significance was considered when p< 0.05. A sub-sample of 10% of the schoolchildren was re-examined for fluorosis and dental caries with one-day intervals between examinations to assess intraexaminer variability; Cohen’s Kappa coefficient was found to be 0.88, indicating a high level of agreement. RESULTS: Dental fluorosis Table 2 is copied directly from Acharya (2005) showing the prevalence and severity of fluorosis associated with exposure to water with varying fluoride concentrations. The prevalence of fluorosis increased from 16% at 0.43 ppm F to 100% at 3.41 ppm F and the degree of fluorosis severity increased as fluoride levels increased. The Community Fluorosis Index (CFI) increased from 0.10 at 0.43 ppm F to 2.10 at 3.41 ppm F, making the 3.41 ppm community one of marked health significance. PROFILER’S NOTE: The prevalence and severity of fluorosis is given for each village was assessed; however, the greatest variance in data were when fluoride levels went from 1.22 ppm to 3.14 ppm. Acharya (2005) discusses the high level of fluoride present within this region of India due to the use of phosphate fertilizers causing fluoride levels to be increased in foods such as sorghum and rice (Anasuya et al. 1997) and the heavy consumption of tea in India; however, actual consumption of water or these other fluoride sources were not addressed in the study. Dental caries Acharya (2005) states that caries incidence and severity were highest in the children living in the area with the lowest fluoride (0.43 ppm) concentration, and that there was a statistically significant negative (r = -0.16) correlation between water fluoride levels and the mean DMFS, showing a declining trend with increasing level of fluoride (see Table 1 and Figure 1 copied directly from Acharya, 2005). The pit and fissure lesions also showed a decrease with increasing water fluoride levels, however, this trend was not observed with smooth surface lesions. Dental caries also was stated to be more prevalent in the older children and in the females. 7 January, 2008 PROFILER’S NOTE: While the prevalence of caries did decrease as the fluoride level increased, the trend was not as strong for the DMFS score. The mean DMFS score for the 1.10 ppm fluoride level group was actually less than that at 1.22 ppm (see Table 1 above). The biggest difference in caries prevalence and mean DMFS scores was when the lowest and highest fluoride levels were compared. From the data provided, the profiler could not agree that the trend of increasing dental caries with age and in females occurred. Caries surface patterns The number of