Hydrogen sulphide

Neurotoxicity

Description of key information

There is a combined systemic- and reproduction toxicity study according to OECD 421 with H2S availiable (Dorman et al., 2000). In this study not only the systemic toxicity and the toxicity to reproduction was investigated but the animals, especially the pups were also examined for neurotoxicity.
In contrast to all the other neurotoxicity studies in literature an accepted guideline-conform test for evaluation of neurotoxicity had been used.
In this GLP study Dorman et al. (2000) examined the effects of an inhalation exposure to H2S. In this combined systemic- and reproduction toxicity study according to OECD 421 Groups of 12 male and 12 female Sprague-Dawley rats were exposed to hydrogen sulfide at 0, 10, 30, or 80 ppm 6 h/day, 7 days/week for 2 weeks before breeding. Exposures continued during a 2-week mating period and then on GD 0-19. Exposure of the dams and pups (eight rats per litter after culling) resumed from PND 5 to PND 18. Adult male rats were exposed on 70 consecutive days. 
The offspring were evaluated on the basis of motor activity, passive avoidance, a functional observational battery, acoustic startle response, and neuropathology.  There were no gross abnormalities observed at necropsy in the brain, spinal cord, or peripheral nerves of any pup. 
Exposue to H2S did not affect pup growth, development, or performance on any of the behavioral tests.
The results of this study suggests that H2S is neither a reproductive toxicant nor a behavioral developmental neurotoxicant in the rat.
So the NOAEC for the neurotoxic effects was 80 ppm (111 mg/m3).

Additional information

There is a combined systemic- and reproduction toxicity study according to OECD 421 with H2S availiable (Dorman et al., 2000). In this study not only the systemic toxicity and the toxicity to reproduction was investigated but the animals, especially the pups were also examined for neurotoxicity.

In contrast to all the other neurotoxicity studies in literature an accepted guideline-conform test for evaluation of neurotoxicity had been used in this study of Dorman et al. (2000).

The offspring were evaluated using motor activity (postnatal day 13, 17,21 and 60 +-2), passive avoidance (postnatal day 22 +-1, 62 +- 3), functional observation battery (postnatal day 60 +-2), acoustic startle response (postnatal day 21, 62 +-3) and neuropathology (postnatal day 23 +-2, 61 +-2). Additionally specific histopathologic preparations have been used to detect effects on the brain, spinal cord and nerves of the animals.

No relevant gross abnormalities were observed at necropsy in the brain, spinal cord, or peripheral nerves of any pup. Exposue to H2S did not affect pup growth, development, or performance on any of the behavioral tests.

So the NOAEC for the neurotoxic effect was 80 ppm (111 mg/m3).

All the other studies reported in literature were not performed according to a guideline and used much shorter exposition times per day as the study of Dorman et al. (2000). Therefore their results are not comparable to the guideline study and these studies are judged as "not reliable" or as "not assignable" and the results of these studies are not used for the evaluation of the neurotoxicity of H2S.

Based on the respiratory lesions observed in the study with inhalation exposure by Dorman et al. (2000) H2S is calssified as H335: May cause respiratory irritation, according to the CLP-criteria/R37: Irritating to the respiratory system, according to DSD.

Justification for classification or non-classification

According to the available data and CLP/DSD criteria, no classification is warranted for neurotoxic effects.