Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to a method comparable to OECD guideline 413, but not under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Santicizer 154

Test animals

Species:
rat
Strain:
other: Charles River - COBS
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
clean air
Remarks on MMAD:
MMAD / GSD: No data
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
62 exposures of 6 hours (5 days a week for 90 days)
Frequency of treatment:
Once on an exposure day
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
10 and 100 mg/m3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
10.1 and 101.1 mg/m3
Basis:
analytical conc.
No. of animals per sex per dose:
15
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOAEC
Remarks:
systemic
Effect level:
101.1 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No test article-related effects, absence of dose-effect relationship (organ weights)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

- Mortality: No treatment related effects observed

- Clinical signs: Ruffed and discolored fur and ptosis in test groups. High dose group animals exhibited rhinitis, sneezing, wheezing and hemorrahic conjunctivitis.

- Body weight: No difference as compared to the control group

- Hematology: No difference as compared to the control group

- Clinical chemistry: No treatment related effects observed

- Urinalysis: No difference as compared to the control group

- Gross necropsy: No difference as compared to the control group

- Organ weights: Males of the highest dose group had significant higher relative liver weight as compared to control males. No other toxicogically significant effects were found.

- Gross/histopathology: No difference as compared to control group

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, no clear test article- or dose-related effects were observed in rats as a result of exposure to Santicizer 154. Therefore, a NOAEL of 101.1 mg/m3 was established.
Executive summary:

The toxicity of Santicizer 154 was determined in a 90-day inhalation study in rats. Male and female animals were exposed for 6 hours a day, 5 days a week over a period of 90 days (total 62 exposure days) to 0, 10.1 or 101.1 mg/m3 of test article. Mortality, clinical signs, body weights were recorded and gross necropsy was performed in all animals. Hematology, clinical chemistry, urinalysis and histopathology were performed and organ weights were recorded in the high dose and control group.

No test article-related deaths were noted. A ruffed and discolored fur and ptosis in both test groups, while in the high dose group animals exhibited rhinitis, sneezing, wheezing and hemorrahic conjunctivitis. No difference in body weights, hematology parameters, clinical chemistry values and urinalysis parameters were observed as compared to the control group. Gross necropsy showed no differences in both test groups as compared to the control group. Males of the highest dose group had a significant higher relative liver weight as compared to control males. No other toxicologically significant effects were found. No treatment related histopathological effects were observed in the highest dose group as compared to the control group.

Under the conditions of this study, no clear test article- or dose-related effects were observed in rats as a result of exposure to Santicizer 154. Therefore, a NOAEL of 101.1 mg/m3 was established.