Hydrogen sulfide metabolism

Carbon disulfide, hydrogen sulfide, and sulfur dioxide should be handled carefully. Hydrogen sulfide in small concentrations can be metabolized, but in higher concentrations it quickly can cause death by respiratory paralysis. 

The nervous system is vulnerable to attack from several directions. Neurons do not divide, and, therefore, death of a neuron always causes a permanent loss of a cell. The brain has a high demand for oxy gen. Lack of oxygen (hypoxia) rapidly causes brain damage. This manifests itself both on neurons and oligodendroglial cells. Anoxic brain damage may result from acute carbon monoxide, cyanide, and hydrogen sulfide poisonings. Carbon monoxide may also be formed in situ in the metabolism of dichloromethylene. 

Organisms also evolved powerful detoxifying mechanisms that remove toxic materials or convert them to non-toxic forms or nutrients. Examples of alterations to non-toxic forms are the conversions of hydrogen sulfide to sulfate and nitrite to nitrate. The prime example of development of the ability to use a toxic substance is the evolution of aerobic metabolism, which converted a serious and widespread toxin, oxygen, into a major resource. This development, as we have seen, greatly increased the productivity of the biosphere and generated the oxygen-rich atmosphere of today s Earth. 

Levels of Significant Exposure to Hydrogen Sulfide - Inhalation 2-2 Levels of Significant Exposure to Hydrogen Sulfide - Oral 2-3 Metabolic Pathways of Hydrogen Sulfide Biotransformation... 

The major metabolic pathway for hydrogen sulfide in the body is the oxidation of sulfide to sulfate, which is excreted in the urine (Beauchamp et al. 1984). The major oxidation product of sulfide is thiosulfate, which is then converted to sulfate the primary location for these reactions is in the liver (Bartholomew et al. 1980). 

FIGURE 2-3. Metabolic Pathways of Hydrogen Sulfide Biotransformation ... 

No studies were located regarding metabolism in humans or animals after oral, dermal, or other routes of exposure to hydrogen sulfide. 

Humans may be exposed to hydrogen sulfide both from its endogenous production or from exogenous sources. Most endogenous production apparently results from the metabolism of sulfhydryl-containing amino acids, e.g., cysteine, by bacteria present in both the intestinal tract and the mouth (Beauchamp et al. 1994 Tonzetich and Carpenter 1971) however, it is also produced in the brain and several smooth muscles, e.g., thoraic aorta, by enzymes found in these tissues (Abe and Kimura 1996 Hosoki et al. 1997). 

Metabolic Effects. Severe metabolic acidosis developed in a worker exposed to hydrogen sulfide generated from a sodium sulfide waste solution being dumped onto acid waste material (Stine et al. 

The usefulness of urinary thiosulfate as an indicator of nonfatal hydrogen sulfide toxicity has been studied (Kangas and Savolainen 1987). Urinary samples for thiosulfate were obtained from volunteers exposed by inhalation to 8, 18, or 30 ppm of hydrogen sulfide for 30-45 minutes (the occupational exposure limit of 10 ppm for 8 hours was never exceeded). Excretion of urinary thiosulfate increased linearly up to 15 hours postexposure. Beyond 15 hours, the urinary thiosulfate concentration remained low, possibly indicating that most of the absorbed hydrogen sulfide was metabolized or excreted within 15 hours. 

Alterations in blood heme metabolism have been proposed as a possible indicator of the biological effects of hydrogen sulfide (Jappinen and Tenhunen 1990), but this does not relate to the mechanism of toxicity in humans. The activities of the enzymes of heme synthesis, i.e., delta-aminolevulinic acid synthase (ALA-S) and heme synthase (Haem-S), were examined in 21 cases of acute hydrogen sulfide toxicity in Finnish pulp mill and oil refinery workers. Subjects were exposed to hydrogen sulfide for periods ranging from approximately 1 minute to up to 3.5 hours. Hydrogen sulfide concentrations were considered to be in the range of 20-200 ppm. Several subjects lost consciousness for up to 3 minutes. 

Activities of ALA-S and Haem-S were decreased after exposure to hydrogen sulfide. However, the changes in heme metabolism are not specific for hydrogen sulfide, and other sulfur-containing compounds such as methyl mercaptan can produce similar effects. 

The major metabolic pathway of hydrogen sulfide is the oxidation of the sulfide to sulfate in the liver (Beauchamp et al. 1984). Methylation also serves as a detoxification route. Hydrogen sulfide is excreted primarily as sulfate (either as free sulfate or as thiosulfate) in the urine. 

Hydrogen sulfide inhibits mitochondrial cytochrome oxidase, resulting in disruption of the electron transport chain and impairing oxidative metabolism. Nervous and cardiac tissues, which have the highest oxygen demand (e.g., brain and heart), are especially sensitive to disruption of oxidative metabolism (Ammann 1986 Hall 1996). 

The qualitative data on the absorption, distribution, metabolism, and excretion of hydrogen sulfide in humans and animals are well known. Quantitative data are generally lacking. Additional animal data through collection by quantitative measurements are collected are needed, as well as data on changes in these parameters with exposure. 

Hydrogen sulfide is produced in the large intestine of mammals by metabolism of sulfhydryl proteins by anaerobic bacteria, and may compose 0-10% of intestinal gases (Beauchamp et al. 1984 EPA 1978). It is produced in the human mouth by microbial petrification (Rosenberg et al. 1991). 

Banki K, Elfarra AA, Lash LH, et al. 1986. Metabolism of S-(2-chloro-l,l,2-trifluoroethyl)-L- cysteine to hydrogen sulfide and the role of hydrogen sulfide in S-(2-chloro-l,l,2-trifluoroethyl)-L-cysteine-induced mitochondrial toxicity. Biochem Boughs Res Caiman 138 707-713. 

De Kok LJ, Rennenberg H, Kuiper PJC. 1991. The internal resistance in spinach leaves to atmospheric hydrogen sulfide deposition is determined by metabolic processes. Plant Physiology and Biochemistry 29 463-470. 

Elovaara E, Tossavainen A, Savolainen H. 1978. Effects of subclinical hydrogen sulfide intoxication on mouse brain protein metabolism. Exp Neurol 62 93-98. 

Gagnaire F, Simon P, Bonnet P, et al. 1986. The influence of simultaneous exposure to carbon disulfide and hydrogen sulfide on the peripheral nerve toxicity and metabolism of carbon disulfide in rats. Toxicol Lett 34 175-183. 

Gunina AI. 1957a. The metabolism of hydrogen sulfide (hydrogen sulfide35) injected subcutaneously. Bulletin of Environmental Biology and Medicine 43(2) 176-179. 

---