Considering changes in exposure and sensitivity in an early life cumulative risk assessment.

A cumulative risk assessment is generally intended to address concurrent exposure by all exposure routes to a group of chemicals that share a common mechanism of toxicity. However, the contribution of different exposure routes will change over time. This is most critical when estimating risks to infants and children because their exposure sources change rapidly during the first few years of life because of dietary and behavioral changes. In addition, there may be changes in sensitivity to toxicants during this time period, associated with various developmental stages. Traditional risk assessments do not address this progression. Examples of how these factors might be incorporated into an early life risk assessment are provided for lead, dioxins and furans, and organophosphate pesticides. The same concepts may apply to other potentially susceptible subpopulations, such as the elderly.

Cancer mortality in a Chinese population exposed to hexavalent chromium in drinking water.

BACKGROUND: In 1987, investigators in Liaoning Province, China, reported that mortality rates for all cancer, stomach cancer, and lung cancer in 1970-1978 were higher in villages with hexavalent chromium (Cr+6)-contaminated drinking water than in the general population. The investigators reported rates, but did not report statistical measures of association or precision. METHODS: Using reports and other communications from investigators at the local Jinzhou Health and Anti-Epidemic Station, we obtained data on Cr+6 contamination of groundwater and cancer mortality in 9 study regions near a ferrochromium factory. We estimated: (1) person-years at risk in the study regions, based on census and population growth rate data, (2) mortality counts, based on estimated person-years at risk and previously reported mortality rates, and (3) rate ratios and 95% confidence intervals. RESULTS: The all-cancer mortality rate in the combined 5 study regions with Cr+6-contaminated water was negligibly elevated in comparison with the rate in the 4 combined study regions without contaminated water (rate ratio = 1.13; 95% confidence interval = 0.86-1.46), but was somewhat more elevated in comparison with the whole province (1.23; 0.97-1.53). Stomach cancer mortality in the regions with contaminated water was more substantially elevated in comparison with the regions without contaminated water (1.82; 1.11-2.91) and the whole province (1.69; 1.12-2.44). Lung cancer mortality was slightly elevated in comparison with the unexposed study regions (1.15; 0.62-2.07), and more strongly elevated in comparison with the whole province (1.78; 1.03-2.87). Mortality from other cancers combined was not elevated in comparison with either the unexposed study regions (0.86; 0.53-1.36) or the whole province (0.92; 0.58-1.38). CONCLUSIONS: While these data are limited, they are consistent with increased stomach cancer risk in a population exposed to Crz=6 in drinking water.

Development of a health-protective drinking water level for perchlorate.

We evaluated animal and human toxicity data for perchlorate and identified reduction of thyroidal iodide uptake as the critical end point in the development of a health-protective drinking water level [also known as the public health goal (PHG)] for the chemical. This work was performed under the drinking water program of the Office of Environmental Health Hazard Assessment of the California Environmental Protection Agency. For dose-response characterization, we applied benchmark-dose modeling to human data and determined a point of departure (the 95% lower confidence limit for 5% inhibition of iodide uptake) of 0.0037 mg/kg/day. A PHG of 6 ppb was calculated by using an uncertainty factor of 10, a relative source contribution of 60%, and exposure assumptions specific to pregnant women. The California Department of Health Services will use the PHG, together with other considerations such as economic impact and engineering feasibility, to develop a California maximum contaminant level for perchlorate. We consider the PHG to be adequately protective of sensitive subpopulations, including pregnant women, their fetuses, infants, and people with hypothyroidism.

Can we protect everybody from drinking water contaminants?

Dozens of chemicals, both natural and manmade, are often found in drinking water. Some, such as the natural contaminants uranium and arsenic, are well-known toxicants with a large toxicology database. Other chemicals, such as methyl tertiary-butyl ether (MTBE) from leaking fuel tanks, we learn about as we go along. For still others, such as the alkyl benzenes, there are very little available data, and few prospects of obtaining more. In some cases, chemicals are purposely added to drinking water for beneficial purposes (e.g., chlorine, fluoride, alum), which may cause a countervailing hazard. Removing all potentially toxic chemicals from the water is virtually impossible and is precluded for beneficial uses and for economic reasons. Determination of safe levels of chemicals in drinking water merges the available toxicity data with exposure and human effect assumptions into detailed hazard assessments. This process should incorporate as much conservatism as is needed to allow for uncertainty in the toxicity and exposure estimates. Possible sensitive subpopulations such as unborn children, infants, the elderly, and those with common diseases such as impaired kidney function must also be considered. However, the range of sensitivity and the variability of toxicity and exposure parameters can never be fully documented. In addition, the validity of the low-dose extrapolations, and whether the toxic effect found in animals occurs at all in humans, is never clear. This publication discusses how these competing needs and uncertainties intersect in the development of Public Health Goals for uranium, fluoride, arsenic, perchlorate, and other highly debated chemicals.