Link to Full Document:  http://www.epa.gov/IRIS/toxreviews/0061tr.pdf

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MAJOR CONCLUSIONS IN THE CHARACTERIZATION OF HAZARD AND DOSE RESPONSE

6.1. HAZARD IDENTIFICATION

Hydrogen sulfide is a colorless gas and has a strong odor of rotten eggs. Its primary uses include the production of elemental sulfur and sulfuric acid, the manufacture of heavy water and other chemicals, in metallurgy, and as an analytical reagent. Although quantitative data are lacking, toxicity studies suggest that H2S gas is absorbed rapidly through the lungs. Oral exposure is not likely to occur. In animals and humans, it distributes to the blood, brain, lung, heart, liver, spleen, and kidney. Oxidation is the primary metabolic pathway for H2S, with thiosulfate and sulfate as metabolites. Metabolism in laboratory animals and in humans appears to be similar. Hydrogen sulfide is excreted in the urine.

Human data pertaining to inhalation exposure (the expected route of ambient exposure) consist of a plethora of case reports and a variety of occupational epidemiological studies. Although these studies have limitations that preclude their use for quantitative risk assessment, they indicate that exposure to H2S (at high concentrations) has profound effects on the respiratory system leading to unconsciousness with attendant neurologic sequelae and, sometimes, death. An increase in cardiovascular-related deaths due, in part, to H2S exposure was reported in one occupational study.

Inhalation studies in adult rodents demonstrate sensitivity of nasal olfactory epithelium to low concentrations of H2S. The RfC is based on these lesions. Limited evidence suggests that exposure of humans to low concentrations may also cause neurologic symptoms although quantitative exposure-response data is lacking. Because of similar access of inhaled H2S to the olfactory tissues of humans, these lesions are likely of relevance to humans and a reasonable choice as a critical effect. Relevance to olfactory lesions seen in rodents to humans is also suggested by Hirsch and Zavala (1999) who reported decreased persistent olfactory function in workers exposed to hydrogen sulfide chronically. Whereas adverse nasal effects are of relevance and concern in adult human exposure scenarios, inhalation studies of perinatal or neonatal exposure in rats demonstrates abnormal cellular development in the brain as well as significant alterations in neurotransmitter levels; the toxicological significance of these findings is uncertain.

Relevant quantitative human oral toxicity data are not available and ingestion is not a likely route of exposure. An RfD based on GI disturbances in pigs consuming feed containing hydrogen sulfide was derived in the previous IRIS entry. A review of the RfD (see Section 4.2.1) indicates that the effects on which that value were based are not reproducible and probably not related to H2S. Therefore the previous RfD will be withdrawn and a new RfD will not be derived based on data base deficiencies.

The indicators of a possible effect noted in the developing brain cells of newborn rats indicate the possibility that the developing human fetus could also be at risk. The exposure levels producing these effects, however, are in the same range or somewhat higher than those producing the critical sentinel clearly adverse effect (nasal tract lesions) in adult animals, thereby ameliorating the concern that young animals (and possibly children) may be especially susceptible to the effects from relatively low-level chronic exposures to hydrogen sulfide. Other observations in the data base do indicate a possible concern regarding the susceptibility of children exposed to high levels of H2S, i.e., > 600 ppb. However, the relevance of this apparent susceptibility at environmental levels of H2S where toxicity is not likely to occur, such as the RfC value derived herein, is not at all clear.

There is no evidence indicating that H2S exposure is associated with carcinogenesis. Under the Draft Revised Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1999), data are inadequate for an assessment of the carcinogenic potential of hydrogen sulfide.

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Link to Full Document:  http://www.epa.gov/IRIS/toxreviews/0061tr.pdf