ABSTRACT
The Agency for Toxic Substances and Disease Registry (ATSDR) derives health-based guidance values to estimate daily human exposure to hazardous substances that are likely to be without appreciable risk of adverse noncancer effects for specific routes and durations of exposure. Most of these guidance values are derived from data showing external dose/health effect relationships. However, for chemicals that persist in the body, information on body burdens may provide more accurate understanding of their toxicity. This article evaluates the exposure versus body burden approaches using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and lead as examples.
Subject(s)
Body Burden , Environmental Exposure/analysis , Environmental Pollutants/standards , Lead/standards , Polychlorinated Dibenzodioxins/standards , Animals , Environmental Exposure/adverse effects , Environmental Pollutants/toxicity , Humans , Lead/toxicity , No-Observed-Adverse-Effect Level , Polychlorinated Dibenzodioxins/toxicity , Risk Assessment , UncertaintyABSTRACT
Thimerosal, which releases the ethyl mercury radical as the active species, has been used as a preservative in many currently marketed vaccines throughout the world. Because of concerns that its toxicity could be similar to that of methyl mercury, it is no longer incorporated in many vaccines in the United States. There are reasons to believe, however, that the disposition and toxicity of ethyl mercury compounds, including thimerosal, may differ substantially from those of the methyl form. The current study sought to compare, in neonatal mice, the tissue concentrations, disposition and metabolism of thimerosal with that of methyl mercury. ICR mice were given single intramuscular injections of thimerosal or methyl mercury (1.4 mg Hg kg(-1)) on postnatal day 10 (PND 10). Tissue samples were collected daily on PND 11-14. Most analysed tissues demonstrated different patterns of tissue distribution and a different rate of mercury decomposition. The mean organic mercury in the brain and kidneys was significantly lower in mice treated with thimerosal than in the methyl mercury-treated group. In the brain, thimerosal-exposed mice showed a steady decrease of organic mercury levels following the initial peak, whereas in the methyl mercury-exposed mice, concentrations peaked on day 2 after exposure. In the kidneys, thimerosal-exposed mice retained significantly higher inorganic mercury levels than methyl mercury-treated mice. In the liver both organic and inorganic mercury concentrations were significantly higher in thimerosal-exposed mice than in the methyl mercury group. Ethyl mercury was incorporated into growing hair in a similar manner to methyl mercury. The data showing significant kinetic differences in tissue distribution and metabolism of mercury species challenge the assumption that ethyl mercury is toxicologically identical to methyl mercury.
Subject(s)
Methylmercury Compounds/pharmacokinetics , Thimerosal/pharmacokinetics , Animals , Animals, Newborn , Female , Male , Mice , Mice, Inbred ICR , Tissue DistributionABSTRACT
The Division of Toxicology, Agency for Toxic Substances and Disease Registry (ATSDR) has a Congressional mandate to develop toxicological profiles for chemicals of greatest concern at hazardous waste sites. These chemical profiles provide a comprehensive evaluation and interpretation of the health effects, chemical and physical properties, production and use, potential for human exposure, analytical methodologies, and regulations and advisories for those chemicals. In addition, these profiles identify critical gaps in the knowledge base for these chemicals and identify levels of significant human exposure. Health assessors and other public health officials use this information to make critical decisions regarding the potential for adverse health effects at hazardous waste sites and other chemical-release events through such activities as public health assessments, chemical-specific and health-specific consultations, health-guidance-value derivations, database development, and emergency response actions. In a previous paper, we provided an overview of six specific public-health activities conducted by the ATSDR Division of Toxicology and examined how these activities have made unique impacts on public health policy and service. In this paper, we follow up on two of these, ATSDR polychlorinated biphenyls (PCBs) activities and ATSDR mercury activities, and examine their long-term, continually evolving impacts on public health policy and service.
