Registration Dossier

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
other information
Study period:
data not available
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Synergism between mercaptans and ammonia or fatty acids in the production of coma: a possible role for mercaptans in the pathogenesis of hepatic coma
Author:
Zieve L, Doizaki WM and Zieve FJ
Year:
1974
Bibliographic source:
J Lab Clin Med, 83(1), 16-28

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
no
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
dimethyl sulfide from Eastman Organic Chemicals, Rochester, NY.
Purity was confirmed by injecting the material received into the gas chromatograph and observing a single peak.
No other information available

Test animals

Species:
rat
Strain:
other: Holtzman or Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
rat body weight: 285 to 325 grams
No other information available

Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
not specified
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
data not available
Frequency of treatment:
data not available
Post exposure period:
none
Doses / concentrations
Remarks:
Doses / Concentrations:
6 dose level between 7 and 12% by volume
Basis:
no data
No. of animals per sex per dose:
each point is based upon 3 to 5 rats
Control animals:
no
Details on study design:
Rats were placed singly in a large 4 liter glass chamber.
Blood concentration in dimethyl sulfide was determined

Results and discussion

Details on results:
The CD50 (dose at which 50 percent of animals become comatose) in rats was reported as 9.6% (v/v) dimethyl sulfide in air. The blood level of DMS at which coma occurred was 7 µmol/ml blood. A linear correlation was apparent between blood level and dose administered.
The rats went through a brief excitement phase before they became groggy. With doses producing coma in 50% of animals, the excitement phase lasted approximately 2 minutes, then passed quickly into a phase lasting 1 minute in which the rat became groggy and lethargic. This was followed in the next minutes or two by frank coma, the rat falling to its side and rolling over on its back as the chamber was tipped up slightly. With smaller doses the excitement phase and the pre-coma phase were prolonged; with larger doses the entire sequence occurred more quickly. If the rats were removed from the chamber as soon as he became comatose, the coma did not last more than 30 minutes as a rule, and upon recovery the rat appeared and remained alert and active.

Any other information on results incl. tables

DMS decreased the CD50 of the ammonium ion by approximately 50% and the incidence of coma rose from 0 to 100% when the maximum subcoma dose of DMS

(6.36% in air) and the ammonium ion were given together.

Applicant's summary and conclusion