Hydrogen sulphide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

14 mg/m³

Species:

rat

Quality of whole database:

GLP guideline study

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In a guideline study (OECD 421) with an inhalation exposure of H2S Dorman et al. (2000) determined if perinatal exposure by inhalation to H2S had an adverse effect on reproductive performance and pregnancy outcomes. Virgin male and female Sprague-Dawley rats (12/sex/group) were exposed to 0, 10, 30, or 80 ppm (0, 14, 42, or 111 mg/m3) H2S 6 hr/day, 7 days/week for two weeks prior to breeding. Exposure continued during a 2-week mating period and throughout gestational days 0-19 (GD 0-19). Evidence of copulation (vaginal plug or sperm in vaginal lavage fluid) during the 2-week mating period was considered GD 0. On postnatal day (PND) 4, litters were randomly reduced to 4 animals per sex when possible. Remaining pups were euthanized and discarded without being examined. Dams and pups were then exposed PND 5-18. Nonpregnant adult females were exposed for an additional 23-24 days following the 2-week breeding period. Adult males were exposed to H2S for 70 consecutive days. Clinical examinations were performed on all animals before and after each exposure (Dorman et al., 2000). The body weights of the F0 males and females were determined weekly throughout the study, except that female body weights were not determined weekly once evidence of mating was present. Presumed pregnant females were weighed on GD 0, 7, 14, and 20, and dams were weighed on PND 0, 4, 7, 14, and 21. Feed consumption was determined weekly in F0 males and prebreeding females. Feed consumption in presumed pregnant females was recorded for GD 0-7, 7-14, and 14-20. Dam feed consumption was recorded for PND 0-4, 4-7, 7-14, and 14-21. At the end of exposure, adult rats were euthanized and a complete necropsy was performed with emphasis on reproductive and accessory sex organs. Post-parturient animals were necropsied the day of or the day after weaning. At necropsy, the right testis from each F0 male was examined for sperm number, production, motility, and morphology.

No deaths or adverse clinical signs were observed in F0 males and females for any exposure group. There was a statistically significant decrease in feed consumption in male rats exposed to 80 ppm (111 mg/m3) H2S during the first week of the study. There was a small, but not statistically significant, decrease in body weight (5-6%) observed in F0 males and females exposed to 80 ppm (111 mg/m3) H2S that was present throughout entire exposure period. The only significant difference in organ weights was an increase in absolute and relative adrenal gland weights observed in F0 males exposed to 10 ppm (14 mg/m3) and 80 ppm (111 mg/m3) but not in the mid-dose of H2S and a decrease in the relative ovary weight of females in the 10 ppm (14 mg/m3) exposure group.

There were no statistically significant effects on reproductive performance (mating index, fertility index, postimplantation loss per litter, and number of late resorptions or stillbirths) in F0 animals. Also, the number of live pups, litter size, average length of gestation, and average number of implants per female were not affected. There were no statistically significant effects on sperm production or morphology noted in F0 males; however, a large percentage of abnormal sperm was observed in one F0 male from both the 30 (42 mg/m3) and 80 ppm (111 mg/m3) exposure groups (29 and 73%, respectively). In comparing high-exposure and control animals, there were a few histologic diagnoses with a higher incidence in the high-exposure group, including: testicular tubular degeneration, intratubular sperm stasis, tubular mineralization, sperm granulomas, and multinucleated giant cells, degenerate sperm forms in the lumen, aspermia, and oligospermia. While the incidence of testicular tubular degeneration in high-exposures was higher (42%) than the controls (17%), statistical significance was not achieved. One incidence each of sperm granuloma and unilateral necrosis of the cauda was present in the 80 ppm (111 mg/m3) exposure group. Notable histological findings in females included one each of ovarian cysts and squamous metaplasia of the endometrium in the 10 ppm (14 mg/m3) and 30 ppm (42 mg/m3) exposure groups. The olfactory neuron loss and basal cell hyperplasia observed in the male rats in this study are reported elsewhere (Brenneman et al., 2000). The study considered 12 rats/sex/group. In summary, the reproductive segment of this study did not demonstrate reproductive toxicity in either male or female rats following relatively high H2S exposure of 80 ppm (111 mg/m3) under repeated conditions (up to 70 days for males).

With regards to developmental effects from H2S exposure, there were no statistically significant increases in structural malformations. Observed malformations included kinked tail, agenesis of the tail, anophthalmia, small rear legs and body, frontal bone defects, hypognathia, and skin lesion characterized by detachment of the skin and dermis. However, none of these effects was dose-related. There were no significant differences in pup weight gain or development (pinnae detachment, surface righting, incisor eruption and negative geotaxis, vaginal patency, preputial separation, and eyelid separation). Surface righting was also equivalent across exposure groups. There were no treatment-related effects on motor activity, acoustic startle response, passive avoidance observed, or FOB. Terminal body and organ weights in all exposure groups were comparable to controls. Although a wide variety of gross observations were noted, they were not considered treatment-related by the investigators. Microscopic examination of six levels of the brain from pups from the control and high-dose group failed to demonstrate any histologic abnormalities.

Therefore the NOAEC for the reproductive and developmental toxicity was 80 ppm (111 mg/m3).

Short description of key information:
In a GLP study Dorman et al. (2000) examined the effects on reproductive performance 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.
Offspring were evaluated on the basis of motor activity, passive avoidance, a functional observational battery, acoustic startle response, and neuropathology. There were no deaths and no treatment-related adverse clinical signs in parental males or females. There were no significant effects on reproductive performance of the parental rats as assessed by the number of females with live pups, average gestation length, and average number of implants per pregnant female.

There were no statistically significant effects on reproductive performance (mating index, fertility index, postimplantation loss per litter, and number of late resorptions or stillbirths) in F0 female animals. Also, the number of live pups, litter size, average length of gestation, and average number of implants per female were not affected.
No treatment-related effects in pups were noted in growth, development, or behavioral tests.
No effect on fertility and no other effects were noted at any concentration. The results of this study suggests that H2S is neither a reproductive toxicant nor a behavioral developmental neurotoxicant in the rat.
Therefore the NOAEC for the reproductive and developmental toxicity was 80 ppm (111 mg/m3).

Justification for selection of Effect on fertility via inhalation route:
Key study

Effects on developmental toxicity

Description of key information

In a combined systemic- and reproduction toxicity study according to OECD 421 Groups of 12 male and female rats were exposed to H2S in concentratins of 0, 10, 30 and 80 ppm in the breathing air 6 hours per day on 7 days per week.
There were no deaths and no adverse physical signs observed in F0 male or female rats. There were no statistically significant effects on the reproductive performance of the F0 rats as assessed by the number of females with live pups, litter size, average length of gestation,and the average number of implants per pregnant female.
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. The results of this study suggests that H2S is neither a reproductive toxicant nor a behavior develomental neurotoxicant. So the NOAEC for the reproductive and developmental toxicity was 80 ppm (111 mg/m3).
In the histopathologic examination a significant increase in nasal lesions, such as olfactory neuron loss and basal cell hyperplasia, were observed following exposure to 30 and 80 ppm H2S. So the no-observed adverse effect level with respect to systemic toxicity was 10 ppm (14 mg/m³).

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

111 mg/m³

Species:

rat

Quality of whole database:

reliable. Above NOAEC of 111 mg/m3 is for the reproductive and developmental toxicity.

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

With respect to the data on the toxicity to reproduction of H2S a GLP combined systemic- and reproduction toxicity study according to OECD 421 is availiable. From this study the systemic toxicity as well as the different parts of reproduction toxicity: fertility, developmental toxicity and peri- and postnatal toxicity, can be evaluated.

All the other studies reported in literature were not performed according to a guideline and used a much shorter exposition time 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 toxicity of H2S.

Justification for selection of Effect on developmental toxicity: via inhalation route:
key study

Justification for classification or non-classification

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