Development of California Public Health Goals (PHGs) for chemicals in drinking water.

As part of a program for evaluation of environmental contaminants in drinking water, risk assessments are being conducted to develop Public Health Goals (PHGs) for chemicals in drinking water, based solely on public health considerations. California's Safe Drinking Water Act of 1996 mandated the development of PHGs for over 80 chemicals by 31 December 1999. The law allowed these levels to be set higher or lower than federal maximum contaminant levels (MCLs), including a level of zero if data are insufficient to determine a specific level. The estimated safe levels and toxicological rationale for the first 26 of these chemicals are described here. The chemicals include alachlor, antimony, benzo[a]pyrene, chlordane, copper, cyanide, dalapon, 1,2-dichlorobenzene, 1,4-dichlorobenzene, 2,4-D, diethylhexylphthalate, dinoseb, endothall, ethylbenzene, fluoride, glyphosate, lead, nitrate, nitrite, oxamyl, pentachlorophenol, picloram, trichlorofluoromethane, trichlorotrifluoroethane, uranium and xylene(s). These risk assessments are to be considered by the State of California in revising and developing state MCLs for chemicals in drinking water (which must not exceed federal MCLs). The estimates are also notable for incorporation or consideration of newer guidelines and principles for risk assessment extrapolations.

Neurotoxicology:From the Whole Animal toMolecules.

Neurotoxicity induced by a chemical in vivo is usually produced when the target site within the nervous system is exposed to a sufficient amount of the chemical or its toxic metabolite(s) for a duration of time that is sufficient to result in biological changes. These may be seen as changes in behavior, neurochemistry, neurophysiology, or neuropathology.

Health implications of nitrate and nitrite in drinking water: an update on methemoglobinemia occurrence and reproductive and developmental toxicity.

In 1987, an evaluation of the nitrate drinking water standard was performed with a primary focus on the effects of nitrate on methemoglobinemia and reproductive/developmental effects (Fan et al. (1987). Regul. Toxicol. Pharmacol. 7, 135-148). The present review presents an updated overview and evaluation of the available information on the same health effects of nitrate and nitrite with an emphasis on data not included in the previous review, which should be used as a compendium to this report. Recent epidemiologic data have suggested an association between developmental effects in offspring and the maternal ingestion of nitrate from drinking water, but a definite conclusion on the cause and effect relationship cannot be drawn. Animal experimental data have shown reproductive toxicity associated with high exposure levels to nitrate or nitrite, which are not likely to be encountered in drinking water. No teratogenic effects were observed in rats, mice, rabbits, and hamsters tested. Several cases of methemoglobinemia have been reported in infants in the United States using water containing nitrate at levels higher than the current maximum contaminant level (MCL) of 45 ppm (mg/liter) nitrate (NO3) or 10 ppm nitrate-nitrogen (nitrate-N), but none at or lower than the MCL. The uncertainties in the data base are discussed, noting that no uncertainty factor was applied in deriving the MCL in order to account for the uncertainties that exist in the data base.

Selenium. Nutritional, toxicologic, and clinical aspects.

Despite the recent findings of environmental contamination, selenium toxicosis in humans is exceedingly rare in the United States, with the few known cases resulting from industrial accidents and an episode involving the ingestion of superpotent selenium supplements. Chronic selenosis is essentially unheard of in this country because of the typical diversity of the American diet. Nonetheless, because of the growing public interest in selenium as a dietary supplement and the occurrence of environmental selenium contamination, medical practitioners should be familiar with the nutritional, toxicologic, and clinical aspects of this trace element.

Vitamin A--a pregnancy hazard alert.

Vitamin A is essential to human health, but concerns have arisen recently regarding its potential teratogenicity. Human and animal birth defects have been associated with the use of the vitamin A analogue, isotretinoin, or Accutane, for acne treatment, although the association of such defects with vitamin A itself is unclear. The federal Food and Drug Administration is evaluating the health issues surrounding vitamin A and, together with the manufacturer, has developed restrictions and label warnings to ensure the appropriate use of Accutane. We also have evaluated these issues, with concerns about the possible teratogenicity of high vitamin A intake during pregnancy. Practitioners should be familiar with the possible hazard of excessive dosages of vitamin A and its analogues. Vitamin A daily doses of higher than 8,000 IU for pregnant woman are not necessary for good health and are not recommended. Foods high in beta-carotene can provide the necessary amounts of vitamin A and, in contrast to the synthetic analogues, their use has not been associated with vitamin A toxicity or teratogenicity in humans or animals.

Pesticides and food safety.

This report reviews recent developments regarding the environmental, toxicological, and regulatory issues surrounding pesticide residues in food. Factors affecting the establishment of regulatory limits are discussed. Pesticides monitored by state and federal agencies are compiled and the need for improvements in analytical techniques and enforcement procedures in governmental monitoring programs is pointed out. Specific incidents of concern related to pesticides in food including EDB in grain and grain products, aldicarb in watermelon, demeton-methyl in wine, DDT in fish, S,S,S-tributylphosphorotrithioate in chili peppers, and daminozide in apples and processed apple products are described. The National Academy of Science's study on the Environmental Protection Agency's (EPA) method for setting tolerances for pesticide residues is discussed, especially the dietary cancer risk estimates from pesticides and the inconsistencies in regulating oncogenic pesticides in raw and processed foods existing under the Delaney Clause. The EPA's Tolerance Assessment System is identified to improve the quality of the tolerance establishment process. New California laws to ensure food safety include mandated activities in identifying the toxicological data gaps for pesticides and evaluating pesticide tolerances. Already initiated, tighter regulatory activities at both the federal and the state levels are expected to improve scientific information development, regulatory decisions, and public health protection.

Selenium and human health implications in California's San Joaquin Valley.

An evaluation was conducted on the human health impacts of elevated levels of selenium in the Kesterson National Wildlife Refuge and its surroundings in Merced County, California. Investigative activities of various agencies were summarized and assessed. Agricultural waste water not intended for human use showed elevated selenium concentrations of up to 1400 ppb. Levels of selenium in fish (up to 96 ppm, wet weight), aquatic birds (up to 130 ppm in liver, dry weight), and waterfowl (up to 5.3 ppm flesh, wet weight) were unsafe for unrestricted human consumption. Data on selenium in drinking water (less than 10 ppb), animals (mean values: beef liver 0.3-0.35 ppm, wet weight; milk, 0.01-0.02 ppm), and air (particulate, 14.8 ng/m3; gaseous, less than 1080 ng/m3) did not suggest a high level of exposure. Selenium concentrations in soil were highly variable and suggested a potential source of high exposure. Selenium values in blood and urine of workers were within normal range. A community health survey did not show any trend of adverse health effects in the local population.

Evaluation of the nitrate drinking water standard with reference to infant methemoglobinemia and potential reproductive toxicity.

In view of published results of epidemiologic studies which suggested an association between nitrate in drinking water and human malformations, an assessment of the toxicology of nitrates and nitrites in relation to possible adverse effects on reproduction and development was performed. The current water standard for nitrate is based on protection from methemoglobinemia. A review of the animal data failed to provide evidence for teratogenic effects attributable to nitrate or nitrite ingestion. Adverse reproductive effects reported occurred at doses that were about one thousand times and higher than the estimated human intake. Neither nitrate nor nitrite in experimental animals concentrated in the mammary gland or milk. The present assessment concludes that the maximum contaminant level of 45 ppm nitrate ion, or 10 ppm nitrate-nitrogen, adequately protects the very young from nitrate-induced toxicity, both pre- and postnatally.

Development of a format for abstracting dose-response information from published studies for use in quantitative structure-activity relationships (QSARs).

The Toxic Substances Control Act subjects some 70 000 chemicals to regulatory action. However, empirical testing of the biological activities of this number of compounds is not feasible. An attractive alternative is the development of predictive methodology which can be used to estimate the potency of an untested compound toward a specific biological receptor. Prerequisite to such an enterprise is the highly systematic compilation of dose-response information for a wide range of biological end points and for a wide variety of molecular species. A format is described for abstracting relevant information from published studies. The format outlines the test system, experimental conditions, response analysis, exposure protocol, and results and presents the original data, all in an organized form. Regression analysis is used to estimate thresholds and potencies in the various test systems. The data may then be used to develop a predictive methodology.