Anna M. Fan

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.

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 Sciences study on the Environmental Protection Agencys (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 EPAs 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.

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.

Alar in Fruit: Limited Regulatory Action in the Face of Uncertain Risks

1, 1-Dimethylhydrazine (UDMH) is a breakdown product of daminozide (tradename “Alar”), a plant growth regulator which was used on fruit, most notably apples. The carcinogenic activity of UDMH was first reported in 1967 when lung tumors were noted in UDMH-exposed mice, and then was confirmed in the early 1970s when both lung tumors and hemangiosarcomas were observed in mice. These early findings were again confirmed; hemangiosarcomas in hamsters and lung adenomas in rats were also observed. Because the early studies did not follow good laboratory practice procedures instituted in 1979, the early results were discounted, particularly for quantitative risk estimation, and regulation of daminozide as a carcinogen delayed. In 1987, the EPA published a cancer potency value for UDMH derived from the early mouse study. Using this potency estimate, the Natural Resources Defense Council (NRDC) predicted that average risks to preschoolers from daminozide use approached 1/1000, and widely publicized this finding as unacceptable. As a consequence, apples were soon removed from the luncheon menus of elementary schools and the public voiced general skepticism about the safety of the food supply. In response, EPA, various state agencies and other groups developed their own risk estimates. We discuss the EPA and NRDC assessments and the basis for the differences in their risk estimates, including assumptions concerning risks from early-in-life exposure, the fraction of UDMH derived from daminozide, appropriate subpopulations, representative parameters of the potency distribution, and corrections for bioassay length. It is demonstrated that some plausible estimates of risk, derived from conservative, reasonable assumptions, exceed those developed by EPA and NRDC.

Arsenic: risk assessment for california drinking water standards

Six California counties contain 15 water systems with arsenic concentrations above the 50 ppb Maximum Contaminant Level (MCL). Arsenic compounds are carcinogenic in humans by oral and inhalation routes. They are also fetotoxic and teratogenic in mice, rats and hamsters and cause a variety of toxic effects in the gastro-intestinal tract, circulatory system, skin, liver, kidney, nervous system and heart. The US EPA has identified an oral human chronic No-Observable-Adverse-Effect Level (NOAEL) of 0.0008 mg/kg-d based on skin and vascular effects. In 1988 EPA estimated the human carcinogenic potency of arsenic in drinking water to be about 2 × 10−1/μg/kg-d with a 10−6 lifetime skin cancer risk equivalent to consumption of 21/day at 20 ppt. Recently Smith et al. (1990) estimated the potency of arsenic to be 5.3 × 10−3μ/g/kg-d based on the same human data. Also Chen et al. (1988) and Chen and Wang (1990) identified the additional tumor sites of liver, lung, bladder, kidney, nasal cavity and prostate. The lifetime risk of developing skin cancer at the 50 ppb MCL level (21/day) is about 8 in 1000. Preliminary analysis of the recent data on other tumor sites indicate comparable risks of: females - lung, 11.0; bladder, 6.7; kidney, 3.4; liver, 0.3; males - lung, 6.1, bladder, 2.2; kidney, 1.4; liver, 0.2. On the basis of a skin cancer potency of 5.3 × 10−3/μg/kg-d, a Recommended Public Health Level (RPHL) of 2 ppt (0.002 μg/l) is being proposed in accordance with the provisions of the Safe Drinking Water Act of 1989. This value assumes a body weight of 70 kg, a water consumption of 21/day, a relative source contribution of 20%, and a lifetime extra cancer risk of 10−6.

Chemicals in California drinking water: source contaminants, risk assessment, risk management, and regulatory standards

Abstract Monitoring studies from 1983 to 1992 of water supply and drinking water wells in the state for organic contaminants indicated that more than 80 chemicals were present in ground water. Most of the chemicals detected occurred infrequently and at levels below the current water quality criteria (maximum contaminant level, MCL, or action level, AL). Drinking water wells with levels exceeding these criteria were either closed or had remedial actions taken. Dibromochloropropane (DBCP), simazine, diuron, atrazine, tetrachloroethylene (PCE), and trichloroethylene (TCE) were some of the chemicals detected most frequently in these studies. DBCP, simazine, diuron, and atrazine are agricultural pesticides and are either no longer registered or restricted for use as active ingredients. Special chemical contaminants of concern in ground water are nitrate, arsenic, fluoride, and radon. Surface water from rain and snow runoffs from the Sierra Nevada provides drinking water for most of the San Francisco Bay Area. This water is considered pristine and requires only treatment against disease-causing microorganisms. Most of Southern California depends on surface water from the Sacramento-San Joaquin River Delta and the Colorado River. The quality of water in the Delta is affected by discharges of pollutants into the watersheds of the Sacramento and San Joaquin Rivers and the intrusion of seawater from the San Francisco Bay. The major concern of most water utilities with regard to the use of Delta water for drinking is the formation of trihalomethanes (THMs) and other disinfection by-products. California can promulgate its own regulations which are frequently more stringent than the federal regulations. Standards have also been established for many water contaminants that are uniquely found in California. This report presents the state and federal drinking water standards for 19 inorganic, 66 organic, and 10 other chemicals, mainly radionuclides.

Cumulative Risks and Cumulative Impacts of Environmental Chemical Exposures

As part of the California Environmental Protection Agency (Cal/EPA) effort to address environmental justice issues, the agency has been working to develop methodology to evaluate cumulative impacts of chemical exposures. Cumulative impact analysis takes into account the exposures, public health and/or environmental effects from the combined emissions and discharges of chemicals within a geographic area. Included for considerations are environmental pollution from all sources, whether from a single medium or multiple media, and releases from routine, accidental or other activities. The assessment of the impacts takes into account sensitive populations and socioeconomic factors where appropriate. The assessment of cumulative risks is itself a significant undertaking because it combines health risks from multiple sources of chemical exposures. This is a timely issue as there has been increasing interest to address the concern regarding multiple chemical exposures, sensitive populations, and the methodology to conduct the assessments. In November 2006, we held a symposium at the annual meeting of the American College of Toxicology, Indian Wells, California, entitled, ‘‘Cumulative Risks and Cumulative Impacts of Environmental Chemical Exposures.’’ We discussed the related principles and concepts and methodology currently underway in several toxicology and health assessment program areas in California, particularly in the areas of water and air risk assessment. The presentations covered issues and concerns, cumulative impacts, multiple chemical exposures, and sensitive populations. We addressed our work in progress in the Office of Environmental Health Hazard Assessment, Cal/EPA, which included principles and concepts, methodology, environmental justice, and air-toxics and watercontaminants risk assessment. The articles that follow are based on presentations by the respective authors on the following topics: 1) Perspectives on cumulative impacts and risks; 2) Standard risk assessment procedures: Are they adequate to account for cumulative risks?; 3) Accounting for changing exposure sources in a cumulative risk assessment; and 4) Applying environmental justice principles to risk assessment.

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. Californias 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. Copyright

Regulatory approach to assessing health risks of toxic chemical releases following transportation accidents

Abstract Public health response to transportation accidents in which toxic chemicals are released into the environment require rapid data acquisition and review, health risk assessment, management decisions, and information dissemination. Following a train derailment that resulted in a massive spill of the herbicide metam sodium in the northern Sacramento River, the California Office of Environmental Health Hazard Assessment (OEHHA) was called upon to evaluate the health risks of the parent compound and its breakdown products, and to advise local health agencies in matters of public health concern. This paper describes the approach taken by OEHHA and the public health lessons learned during, and following, the accident.

Integrating risk management and risk communication into a risk assessment of a Medfly eradication project in California

Abstract Health officials are increasingly recognizing that a successful approach to assess and manage health-related issues associated with human exposure to environmental chemicals is to integrate risk assessment, risk management, and risk communication procedures in an overall process to address the specific concerns. The way that risk assessment, risk communication, and risk management were integrated into one project, particularly with the use of an external advisory committee, is described in this article. In 1990, the California Department of Health Services (DHS) evaluated the public health risk of the aerial application of a malathion-bait mixture for eradicating a Mediterranean fruit fly (Medfly) infestation in the greater Los Angeles basin. The department had performed a risk assessment in 1980 on a similar eradication project and had conducted several related epidemiological studies, all of which indicated no adverse health effects from the aerial spraying. However, due to continued concerns about public health and at the request of the executive and legislative branches of state government, DHS prepared a new risk assessment that incorporated review of new scientific studies and the latest risk assessment techniques. As it had done with excellent results in 1980, DHS again convened an external advisory committee. The committees primary purpose was to provide oversight and quality assurance of the risk assessment, but it also became a forum for risk communication and risk management recommendations.