1.
Recommended Reference Values for Risk Assessment of Oral Exposure to Copper.
Taylor, AA, Tsuji, JS, McArdle, ME, Adams, WJ, Goodfellow, WL
Risk analysis : an official publication of the Society for Risk Analysis. 2023;(2):211-218
Abstract
The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) database, the authoritative source of U.S. risk assessment toxicity factors, currently lacks an oral reference dose (RfD) for copper. In the absence of such a value, various health-based reference values for copper are available for use in risk assessment. We summarize the scientific bases and differences in assumptions among key reference values for ingested copper to guide selection of appropriate values for risk assessment. A comprehensive review of the scientific literature best supports the oral RfD of 0.04 mg/kg body weight/day derived by EPA from their Drinking Water Action Level. This value is based on acute gastrointestinal effects but is further supported by broader analysis of copper deficiency and toxicity.
2.
Low-level arsenic exposure and developmental neurotoxicity in children: A systematic review and risk assessment.
Tsuji, JS, Garry, MR, Perez, V, Chang, ET
Toxicology. 2015;:91-107
Abstract
UNLABELLED Risk assessments of arsenic have focused on skin, bladder, and lung cancers and skin lesions as the sensitive cancer and non-cancer health endpoints, respectively; however, an increasing number of epidemiologic studies that can inform risk assessment have examined neurodevelopmental effects in children. We conducted a systematic review and risk assessment based on the epidemiologic literature on possible neurodevelopmental effects at lower arsenic exposures. Twenty-four cross-sectional, case-control, and cohort studies were identified that report on the association between low-level arsenic exposure (i.e., largely <100 μg/L of arsenic in drinking water) and neurological outcomes in children. Although the overall evidence does not consistently show a causal dose-response relationship at low doses, the most rigorously conducted studies from Bangladesh indicate possible inverse associations with cognitive function, predominantly involving concurrent arsenic exposure as measured by biomarkers (i.e., arsenic in urine or blood) and raw verbal test scores at ages 5-11 years. Issues such as non-comparability of outcome measures across studies; inaccuracies of biomarkers and other measures of inorganic arsenic exposure; potential effect modification by cultural practices; insufficient adjustment for nutritional deficiencies, maternal IQ, and other important confounders; and presence of other neurotoxicants in foreign populations limit generalizability to U.S. POPULATIONS Of the few U.S. studies available, the most rigorously conducted study did not find a consistent dose-response relationship between arsenic concentrations in tap water or toenails and decrements in IQ scores. Assuming that the strongest dose-response relationship from the most rigorous evidence from Bangladesh is generalizable to U.S. populations, possible reference doses were estimated in the range of 0.0004-0.001 mg/kg-day. These doses are higher than the U.S. Environmental Protection Agency reference dose for chronic lifetime exposure, thus indicating protectiveness of the existing value for potential neurotoxicity in children. This reference dose is undergoing revision as EPA considers various health endpoints in the reassessment of inorganic arsenic health risks.
3.
Association of low-level arsenic exposure in drinking water with cardiovascular disease: a systematic review and risk assessment.
Tsuji, JS, Perez, V, Garry, MR, Alexander, DD
Toxicology. 2014;:78-94
Abstract
The U.S. Environmental Protection Agency (EPA) is developing an integrated assessment of non-cancer and cancer risk assessment of inorganic arsenic (iAs). Cardiovascular disease (CVD) in association with iAs exposure has been examined in a number of studies and provides a basis for evaluating a reference dose (RfD) for assessing potential non-cancer health risks of arsenic exposure. In this systematic review of low-level iAs exposure (i.e., <100-150μg/L arsenic water concentration) and CVD in human populations, 13 cohort and case-control studies from the United States, Taiwan, Bangladesh, and China were identified and critically examined for evidence for derivation of a RfD. Eight cross-sectional and ecological studies from the United States were also examined for additional information. Prospective cohort data from Bangladesh provided the strongest evidence for determining the point of departure in establishing a candidate RfD based on a combined endpoint of mortality from "ischemic heart disease and other heart diseases." This study as well as the overall literature supported a no-observed-adverse-effect level of 100μg/L for arsenic in water, which was equivalent to an iAs dose of 0.009mg/kg-day (based on population-specific water consumption rates and dietary iAs intake). The study population was likely sensitive to arsenic toxicity because of nutritional deficiencies affecting arsenic methylation and one-carbon metabolism, as well as increasing CVD risk. Evidence is less clear on the interaction of CVD risk factors in the United States (e.g., diabetes, obesity, and hypertension) with arsenic at low doses. Potential uncertainty factors up to 3 resulted in a RfD for CVD in the range of 0.003-0.009mg/kg-day. Although caution should be exercised in extrapolating these results to the U.S. general population, these doses allow a margin of exposure that is 10-30 times the current RfD derived by EPA (based on skin lesions in Southwest Taiwan). These findings suggest that the current EPA RfD is protective of CVD.