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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Version / remarks:
not specified, ntp study
Principles of method if other than guideline:
Preliminary study before 2 years study by NTP (1990)
GLP compliance:
not specified
Remarks:
NTP study
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Specific details on test material used for the study:
CS2 is 94% o-chlorobenzalmalononitrile (CAS No. 2698-41-1) formulated in a mixture of 5% Cab-0-Sil@ colloidal silica and 1% hexamethyldisilizane (CAS No. 999-97-3). No more details are specified.
No impurities were detected by either thin-layer chromatographic system. Gas chromatographic system 1indicated three unresolved impurities after the major peak, with combined areas of 0.09%relative to the major peak area. Gas chromatographic system 2 indicated two impurities, one before and one after the major peak, with a combined relative area of 0.08%.

Test animals

Species:
other: mise and rats
Strain:
other: Male and female F344/N rats and B6C3F1 mice
Details on species / strain selection:
obtained from the Frederick Cancer Research Facility.
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other:

Results and discussion

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEC
Effect level:
>= 0.075 - <= 0.75 mg/m³ air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
Key result
Dose descriptor:
LOEC
Effect level:
ca. 3 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality
body weight and weight gain

Target system / organ toxicity

Key result
Critical effects observed:
no
Lowest effective dose / conc.:
3 mg/m³ air
System:
respiratory system: upper respiratory tract
Organ:
not specified

Applicant's summary and conclusion

Conclusions:
Thirteen-Week Studies by NTP (1990): because of decreased body weight gain and deaths observed at higher concentrations, exposure concentrations selected for rats for the 2-year studies were 0.075, 0.25, and 0.75 mg/m3, 6 hours per day, 5 days per week. Even though the exposure at highest concentration selected (0.75 mg/m31 resulted in na- sal lesions, their severity was minimal and they were not considered to be life threatening.
Executive summary:

Thirteen-Week Studies by NTP (1990): At exposure concentrations of 0, 0.4, 0.75, 1.5, 3, or 6 mg/m3, 1/10 male rats exposed to 6 mg/m3 died before the end of the studies. Final mean body weights of rats exposed to 1.5 mg/m3 or more were 17%-44% lower than that of controls for males and 10%-24% lower for females. The absolute and relative thymus weights were reduced for exposed male and female rats, particularly at 6 mg/m3. Compound-related lesions of the nasal passage in rats included focal erosion with regenerative hyperplasia and squamous metaplasia of the respiratory epithelium and suppurative inflammation. Acute inflammation and hyperplasia of the respiratory epithelium were seen in the larynx and trachea of some exposed rats.

All mice exposed to 6 mg/m3 and 1/10 males and 1/10 females exposed to 3 mg/m3 died before the end of the studies, Final mean body weights of mice exposed to 3 mg/m3 were 13% lower than that of controls for males and 9% lower for females. Compound-related lesions of the nasal passage in mice included squamous metaplasia of the nasal respiratory epithelium and inflammation.