Hydrogen sulphide

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

There are a number of problems with this study. For example, a 75 to 100% incidence of pneumonia was reported in the vehicle control and treated groups, however, a 0% incidence of pneumonia was reported for the non gavaged, rack control group. This information indicates procedural problems with the dosing of the animals. Also, there was one group where mortality was 50%, the high dose male group. However, the cause of death was not determined. In addition, a malady diagnosed as ulcerative dermatitis was common across all groups. Good Laboratory Practice would preclude the acceptance of data from such diseased animals for drawing conclusions regarding the effects of H2S.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1987

Reference 2

Reference Type:

secondary source

Title:

TOXICOLOGICAL REVIEW OF HYDROGEN SULFIDE (CAS No. 7783-06-4). In Support of Summary Information on the Integrated Risk Information System (IRIS)

Author:

U.S. Environmental Protection Agency

Year:

2003

Bibliographic source:

EPA/635/R-03/005. www.epa.gov/iris

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen sulphide

EC Number:

231-977-3

EC Name:

Hydrogen sulphide

Cas Number:

7783-06-4

Molecular formula:

H2S

IUPAC Name:

hydrogen sulfide

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 3.5, or 7 mg/kg/day
Basis:
actual ingested

Control animals:

yes, concurrent vehicle

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

Male and female Sprague-Dawley rats (20/sex/dose group) were administered 0, 1, 3.5, or 7 mg/kg-day H2S by gavage daily for 89 days. Dose-levels were determined after a 14-day range-finding study. Hydrogen sulfide doses were prepared by purging deoxygenated deionized water with pure H2S gas. Prepared H2S solutions were stored in amber vials with Teflon seals and fresh vials were used at each dose administration. Dosing solutions were prepared weekly and solution stability was determined. Animals were examined for mortality at the beginning and end of each working day, and clinical signs were monitored immediately after dose administration. Food consumption of 10 rats per dose group was determined weekly. Animals were weighed weekly during the treatment period and at necropsy. Blood samples were collected from the suborbital sinus of animals prior to study initiation, days 27 to 31 of treatment, and before necropsy. Blood and platelet counts were determined, and clinical chemistry was performed. At study termination, animals were sacrificed by carbon dioxide asphyxiation. Sacrificed animals and animals that died during the treatment period were subjected to a full necropsy. In control and high-dose animals, liver, kidney, spleen, gonad, 19 -20-brain, heart, adrenal, and gross lesions were examined microscopically. In the low- and mid-dose groups, only lung, kidney, liver, and gross lesions were examined microscopically. Mortality was 50% in the high-dose males compared to 5% in control males. No deaths were observed in high-dose females. Mortality in mid-dose males and females was 10 and 5%, respectively, and no deaths were observed in low-dose animals or control females.

Compound-related neuromuscular and behavioral signs were observed in high-dose male and female animals, with the males displaying a higher incidence of these effects (Anderson, 1987). High dose-males exhibited abnormal posture, convulsions, fist clutching, sedation, unusual vocalization, piloerection, labored breathing, and increased respiratory rates. High-dose females exhibited convulsion, sedation, and labored respiration. Although restlessness was observed in all treated males, and increased salivation in all treated females, these clinical signs generally occurred sporadically, and the incidence of these findings did not show a clear dose-response. Therefore, the toxicological significance of restlessness in treated males, and salivation in treated females, is not clear. No significant differences in body weights were noted in any of the treated animals. In addition, no differences in food consumption were noted between treated and control groups. There were no treatment-related effects in hematology or clinical chemistry.

Ophthalmological findings prior to sacrifice were normal. The most common findings at necropsy were pink and red mottled lungs, which occurred in all groups. In high-dose males that died prior to sacrifice, pink-red discoloration of the lungs, nasal discharge, penile discharge, reddening of the scrotal sac, and darkening of the spleen were noted. Although absolute organ weights were not affected by treatment, relative heart weights increased (p< in high-dose males, and relative kidney weights increased (p< 0.05) in high-dose females. No gross lesions could be attributed to compound administration and all microscopic findings were considered incidental to compound administration.