ABSTRACT
Exposures to high levels of manganese by ingestion or inhalation can damage the central nervous system. However, the capacity of environmental manganese to cause neurotoxicity is of most concern following inhalation exposure. Reference exposure levels (RELs) are values developed by California EPA's Office of Environmental Health Hazard Assessment (OEHHA) to protect the general public from periodic and continual exposures to airborne toxicants. The recently revised guidelines for the development of noncancer RELs encourage the use of benchmark dose methodology where appropriate, and explicitly address the potential susceptibilities associated with early-life exposures (OEHHA, 2008). This paper describes the application of those guidelines to the derivation of RELs to protect the general public from routine 8h and chronic exposures to airborne manganese. The data were amenable to benchmark analysis and the RELs derived reflect the mounting evidence that children represent a population that is differentially susceptible to manganese toxicity.
Subject(s)
Air Pollutants, Occupational/toxicity , Inhalation Exposure/analysis , Occupational Exposure/analysis , Oxides/toxicity , Air Pollutants, Occupational/analysis , Belgium , Benchmarking , Cross-Sectional Studies , Humans , Inhalation Exposure/adverse effects , Manganese Compounds/analysis , Neurotoxicity Syndromes/epidemiology , Neurotoxicity Syndromes/etiology , No-Observed-Adverse-Effect Level , Occupational Exposure/adverse effects , Oxides/analysis , Particle Size , Threshold Limit Values , Workplace/standardsABSTRACT
Whether or not children are at higher risk from exposure to air pollutants has become a central question in regulatory toxicology. In order to examine this issue for essential metals several questions related to toxicokinetics and toxicodynamics need to be addressed. These include (1) whether exposure patterns among infants and children are likely to result in disproportionately high exposures to substances in ambient air, and (2) whether infants display special susceptibilities in comparison to the general population. In addition, differences in how developing systems handle metals compared to adults, and interactions between specific metals and other substances with common mechanisms, need to be considered. This study examined the toxicodynamic differences between adults and infants exposed to manganese via inhalation and/or dietary routes of exposure.
Subject(s)
Age Distribution , Air Pollutants/adverse effects , Manganese/adverse effects , Adolescent , Adult , Air Pollutants/pharmacokinetics , Child , Child, Preschool , Environmental Exposure , Humans , Infant , Infant, Newborn , Inhalation Exposure , Manganese/pharmacokinetics , Middle Aged , Pharmacokinetics , Risk Assessment , Young AdultABSTRACT
BACKGROUND: The California Environmental Protection Agency (Cal/EPA) recently completed a health effects assessment of exposure to environmental tobacco smoke (ETS) which resulted in California listing ETS as a Toxic Air Contaminant in January 2006. As part of the assessment, studies on the association between exposure to ETS and breast cancer were reviewed. METHODS: Twenty-six published reports (including 3 meta-analyses) evaluating the association between ETS exposure and breast cancer were reviewed. A weight-of-evidence approach was applied to evaluate the data and draw conclusions about the association between breast cancer and ETS exposure. RESULTS: The published data indicate an association between ETS and breast cancer in younger primarily premenopausal women. Thirteen of 14 studies (10 case-control and four cohort) that allowed analysis by menopausal status reported elevated risk estimates for breast cancer in premenopausal women, seven of which were statistically significant. Our meta-analyses indicated elevated summary relative risks ranging from OR 1.68 (95% C.I. 1.31, 2.15) for all 14 studies to 2.20 (95% C.I. 1.69, 2.87) for those with the best exposure assessment. CONCLUSIONS: Cal/EPA concluded that regular ETS exposure is causally related to breast cancer diagnosed in younger, primarily premenopausal women and that the association is not likely explained by bias or confounding.
