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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
cytotoxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: only secondary literature

Data source

Reference
Reference Type:
publication
Title:
Effects of inhalation exposure to dimethyl sulphate on nasal epithelial cell proliferation.
Author:
Frame, S.R. et al.
Year:
1993
Bibliographic source:
Toxicologist 13, 389 (abstract 1524)

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no
Type of method:
in vivo
Endpoint addressed:
repeated dose toxicity: inhalation

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dimethyl sulphate
No further details were stated.

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No further details were stated.

Administration / exposure

Route of administration:
inhalation
Vehicle:
not specified
Details on exposure:
Rats were exposed nose-only for two weeks to DMS vapors excluding the weekend. Following the seventh exposure, osmotic minipumps containing 5-bromo-2'-deoxyuridine (BrdU) were implanted into the dorsal subcutis. Rats were exposed for an additional three days and sacrifieced 18 hours following the last exposure.
No further details were stated.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No further details were stated.
Duration of treatment / exposure:
14 days
Frequency of treatment:
6 hours/day, 5 day/week
Post exposure period:
18 hours
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.0 mg/m^3
Basis:

Remarks:
Doses / Concentrations:
0.1 mg/m^3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
3.7 ng/m^3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
6.3 mg/m^3
Basis:
nominal conc.
No. of animals per sex per dose:
No further details were stated.
Control animals:
yes
Details on study design:
No further details were stated.

Examinations

Examinations:
Nasal tissue was processed for routine histopathology and immunohistochemical analysis of BrdU incorporation. Labeling indexes were generated from epithelial areas lining the dorsal meatus (olfactory epithelium) and nasoturbinate (respiratory epithelium).
No further details were stated.
Positive control:
No further details were stated.

Results and discussion

Details on results:
DMS was found to induce nasal epithelial cell proliferation at all concentrations tested (0.5, 3.7 and 6.3 mg/m3 6hr/day 5 d/wk). The 2.0- 3.7 fold increase in 2-bromo-5’ deoxyuridine (BrdU) incorporation in nasal epithelium is larger than from DNA repair only. In respiratoy epithelium BrdU incorporation was statistically increased in the highest exposure group only. At the two highest exposure concentrations lesions of the nasal and respiratory epithelium were found, including erosion, ulceration, and atrophy, which increased in severity with exposure concentration and decreased in severity from anterior to posterior regions. Hypertrophy, hyperplasia, and squamous metaplasia were observed in the respiratory epithelium only.

Applicant's summary and conclusion