Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Unpublished study report cited in a peer-reviewed publication
Qualifier:
no guideline followed
Principles of method if other than guideline:
see below
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Weight at study initiation: ca. 140 g
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
clean air
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
not further specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
7 hrs
Frequency of treatment:
five 7 hour periods per week over 4 weeks
Remarks:
Doses / Concentrations:
18995 mg/m3
Basis:
nominal conc.
No. of animals per sex per dose:
10 m / 10 f
Control animals:
yes, concurrent vehicle
Details on study design:
not further specified
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: yes (daily)
DETAILED CLINICAL OBSERVATIONS: yes (daily)
BODY WEIGHT: yes (weekly)
FOOD CONSUMPTION: no data
FOOD EFFICIENCY: no data
WATER CONSUMPTION: no data
OPHTHALMOSCOPIC EXAMINATION: no data
HAEMATOLOGY: yes (at termination)
CLINICAL CHEMISTRY: yes (at termination)
URINALYSIS: no data
NEUROBEHAVIOURAL EXAMINATION: no data
Sacrifice and pathology:
internal organs were weighed and examined macroscopically
Statistics:
no data
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Dose descriptor:
NOAEC
Effect level:
18 995 mg/m³ air
Sex:
male/female
Critical effects observed:
not specified
Conclusions:
In a vapour inhalation study, groups of 10 male and 10 female rats were exposed to a concentration of 0 or 18995 mg/m3 on 7 hours/day on 5 days/week over 4 weeks. The treatment gave no indications for adverse effects concerning clinical symptoms or behaviour, body weight gain, blood composition or clinical-chemical parameters. At necropsy, the microscopic examination of internal organs showed no adverse effects and also organ weights were unchanged.
Executive summary:
In a vapour inhalation study, groups of 10 male and 10 female rats were exposed to a concentration of 0 or 18995 mg/m3 on 7 hours/day on 5 days/week over 4 weeks. The treatment gave no indications for adverse effects concerning clinical symptoms or behaviour, body weight gain, blood composition or clinical-chemical parameters. At necropsy, the microscopic examination of internal organs showed no adverse effects and also organ weights were unchanged.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
18 995 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Unpublished study report cited in a peer-reviewed publication
Qualifier:
no guideline followed
Principles of method if other than guideline:
see below
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Weight at study initiation: ca. 140 g
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
clean air
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
not further specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
7 hrs
Frequency of treatment:
five 7 hour periods per week over 4 weeks
Remarks:
Doses / Concentrations:
18995 mg/m3
Basis:
nominal conc.
No. of animals per sex per dose:
10 m / 10 f
Control animals:
yes, concurrent vehicle
Details on study design:
not further specified
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: yes (daily)
DETAILED CLINICAL OBSERVATIONS: yes (daily)
BODY WEIGHT: yes (weekly)
FOOD CONSUMPTION: no data
FOOD EFFICIENCY: no data
WATER CONSUMPTION: no data
OPHTHALMOSCOPIC EXAMINATION: no data
HAEMATOLOGY: yes (at termination)
CLINICAL CHEMISTRY: yes (at termination)
URINALYSIS: no data
NEUROBEHAVIOURAL EXAMINATION: no data
Sacrifice and pathology:
internal organs were weighed and examined macroscopically
Statistics:
no data
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Dose descriptor:
NOAEC
Effect level:
18 995 mg/m³ air
Sex:
male/female
Critical effects observed:
not specified
Conclusions:
In a vapour inhalation study, groups of 10 male and 10 female rats were exposed to a concentration of 0 or 18995 mg/m3 on 7 hours/day on 5 days/week over 4 weeks. The treatment gave no indications for adverse effects concerning clinical symptoms or behaviour, body weight gain, blood composition or clinical-chemical parameters. At necropsy, the microscopic examination of internal organs showed no adverse effects and also organ weights were unchanged.
Executive summary:
In a vapour inhalation study, groups of 10 male and 10 female rats were exposed to a concentration of 0 or 18995 mg/m3 on 7 hours/day on 5 days/week over 4 weeks. The treatment gave no indications for adverse effects concerning clinical symptoms or behaviour, body weight gain, blood composition or clinical-chemical parameters. At necropsy, the microscopic examination of internal organs showed no adverse effects and also organ weights were unchanged.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
18 995 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a vapour inhalation study, groups of 10 male and 10 female rats were exposed to a concentration of 0 or 18995 mg/m3 on 7 hours/day on 5 days/week over 4 weeks. The treatment gave no indications for adverse effects concerning clinical symptoms or behaviour, body weight gain, blood composition or clinical-chemical parameters. At necropsy, the microscopic examination of internal organs showed no adverse effects and also organ weights were unchanged.

No testing of repeated oral toxicity is required since valid data on long-term (carcinogenicity) oral toxicity are available.

No testing of repeated dermal toxicity is required since valid data on long-term (carcinogenicity) oral toxicity are available.

Justification for classification or non-classification

Due to the effect levels obtained in the subacute inhalation toxicity studies, no classification according to EU and GHS criteria is required.