Hydrogen sulphide

Endpoint summary

Description of key information

Human exposure to exogenous hydrogen sulfide is principally via inhalation, and the gas is rapidly absorbed through the lungs. Hydrogen sulfide is metabolized through three pathways: oxidation, methylation, and reactions with metalloproteins or disulfide-containing proteins. Oxidation in the liver is the major detoxification pathway. The major oxidation product is thiosulfate, which is then converted to sulfate and excreted in the urine. The methylation pathway also serves as a detoxification route. The toxicity of hydrogen sulfide is a result of its reaction with metalloenzymes. In the mitochondria, cytochrome oxidase, the final enzyme in the respiratory chain, is inhibited by hydrogen sulfide; this disrupts the electron transport chain and impairs oxidative metabolism. Nervous and cardiac tissues, which have the highest oxygen demand, are especially sensitive to the disruption of oxidative metabolism. In the central nervous system, this effect may result in death from respiratory arrest (WHO, 2003). 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

As summarized in the Concise International Chemical Assessment Document #53 (WHO, 2003).

Inhalation is the most common route of exogenous hydrogen sulfide exposure. Hydrogen sulfide is rapidly absorbed through the lungs in humans. It can also be absorbed through the gastrointestinal tract (ATSDR, 1999). At physiological pH, hydrogen sulfide is dissociated to the hydrogen sulfide anion in the circulation, which is probably the absorbed form (WHO, 2000). In animals, absorption of hydrogen sulfide via the lungs also occurs readily and rapidly (Beck et al., 1979; Khan et al., 1990; Kage et al., 1992). The distribution of inhaled hydrogen sulfide is rapid and widespread; storage of hydrogen sulfide in the body is limited by rapid metabolism and excretion (Nagata et al., 1990). Male Wistar rats exposed through an inhaler to hydrogen sulfide at 110 mg/m³for 20, 40, or 60 min showed essentially the same ratios of distribution of hydrogen sulfide, irrespective of duration. The hydrogen sulfide concentration was highest in the heart, and the level in brain was comparable to the levels in lung, liver, kidney, and spleen. The tissue levels after 20 min of exposure were 10 µg/ml in blood, 25 µg/g in brain, 20 µg/g in lung, 37 µg/g in heart, 20 µg/g in liver, 25 µg/g in spleen, and 30 µg/g in kidney (Kohno et al., 1991). Hydrogen sulfide levels of 0.92 µg/g in blood, 1.06 µg/g in brain, 0.34 µg/g in kidney, and 0.38 µg/g in liver were detected at autopsy in a man who was overcome by hydrogen sulfide after working for 5 min in a tank (Winek et al., 1968). Hydrogen sulfide concentrations in the tank after the accident were 2700–8500 mg/m³.

Hydrogen sulfide is metabolized through three pathways: oxidation, methylation, and reactions with metalloproteins or disulfide-containing proteins (Beauchamp et al., 1984). The major metabolic pathway for detoxification of hydrogen sulfide is oxidation in the liver; the major oxidation product of sulfide is thiosulfate, which is then converted to sulfate and subsequently excreted in urine (Bartholomew et al., 1980). The methylation pathway also serves as a detoxification route (Weisiger & Jacoby, 1980; US EPA, 1987). Reaction with metalloproteins is a major mechanism of toxicity of hydrogen sulfide. Hydrogen also reduces disulfide bridges in proteins. Oxidized glutathione protects against hydrogen sulfide poisoning. Hydrogen sulfide is excreted primarily as sulfate (free sulfate or thiosulfate) in the urine. It is also excreted unchanged in exhaled air and in faeces and flatus. Thiosulfate in urine is a useful indicator of hydrogen sulfide exposure (Kage et al., 1997). Thiosulfate excretion was measured in volunteers exposed to 11, 25, or 42 mg hydrogen sulfide/m³for 30–45 min and compared with that of unexposed individuals at a pelt processing plant (Kangas & Savolainen, 1987). The study did not report the summary results of all exposed individuals; however, data from one individual exposed to 25 mg hydrogen sulfide/m³for 30 min found urinary thiosulfate concentrations of approximately 2, 4, 7, 50, and 5 mmol/mol creatinine at 1, 2, 5, 15, and 17 h post-exposure, respectively. Urinary thiosulfate excreted in controls was 2.9 ± 2.5 (standard deviation [SD]) mmol/mol creatinine (n= 29). In this one individual, therefore, the highest urinary thiosulfate level occurred 15 h after exposure and dropped to control levels by 17 h post-exposure; most absorbed hydrogen sulfide was already oxidized by 15 h post-exposure. The delayed oxidation product thiosulfate buildup is consistent with the metabolic pathway of hydrogen sulfide, which included at least two oxidation steps (Beauchamp et al., 1984).

Evidence for the methylation of hydrogen sulfide comes primarily from in vitro studies of Sprague-Dawley rat intestinal mucosa (Weisiger et al., 1980). Thiol S-methyltransferase catalysed the methylation of hydrogen sulfide to methanethiol (CH₃SH). Methanethiol can act as a substrate for another methylation that is also catalysed by thiol S-methyltransferase, yielding dimethylsulfide (CH₃SCH₃) (Weisiger & Jacoby, 1980; US EPA, 1987). The activity of thiol S-methyltransferase was widely distributed, with the greatest activity being found in the caecal and colonic mucosa, liver, lung, and kidney; enzyme activity was also found in other parts of the intestine and stomach, spleen, heart, and skeletal muscle. No enzyme activity was found in the faeces. Although it has been postulated that methylation is a method of detoxification of hydrogen sulfide, a constituent of human flatus produced in the intestine, the extent to which the toxicity of exogenous hydrogen sulfide is attenuated by methylation is not known.