Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published abstract

Data source

Reference
Reference Type:
publication
Title:
Inhalation toxicity of cyclohexene
Author:
Laham, S.
Year:
1976
Bibliographic source:
Toxicology and Applied Pharmacology 37, 155 - 156

Materials and methods

Principles of method if other than guideline:
In a 6-month repeated dose inhalation study groups of male rats (20 per group), male guinea pigs (10 per group) and rabbits (6 per group) were exposed to cyclohexene in inhalation chambers for 6hr/day on 5 days/week. Dose levels were 75, 150, 300 and 600 ppm (corresponding to 3.3, 6.7, 13.4 and 26.7 mmol/m³) and appropriate control groups exposed to air in similar chambers. Exposure levels were analysed by gas chromatography.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: rat, rabbit, guinea pigs
Strain:
not specified
Sex:
male

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
other: no data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Cyclohexene levels were determined by continous monitoring of the chambers using an automatic sampling system connected to a gas chromatograph
Duration of treatment / exposure:
6hr per day, 5 days per week, for 6 six months
Frequency of treatment:
5 days per week, for 6 six months
Doses / concentrations
Remarks:
Doses / Concentrations:
75ppm, 150ppm, 300ppm, 600ppm
Basis:
no data
No. of animals per sex per dose:
20 male rats per dose level
10 male guinea pigs per dose level
6 male rabbits per dose level
Control animals:
yes, sham-exposed
Details on study design:
Cyclohexene levels were determined by contnous monitoring using an automated sampling system connected to a gas chromatograph
Humidity, pressure and temperature were also monitored inside and outside the chambers

Examinations

Observations and examinations performed and frequency:
Bodyweights were recorded weekly
Haematologic profile (WBC, RBC, PI, Hb, Ht, differenmial count) obtained before during and after exposure
Biochemical profile (glucose, BUN, cholesterol, SGPT, SGOT, LDH, alkaline phosphatase etc) after 6 months exposure
Sacrifice and pathology:
Gross pathology of haemopoietic organs
Statistics:
significance tests

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
reduced body weights for rats at 600 ppm
Food consumption and compound intake (if feeding study):
no effects observed
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:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
No signifcant changes were observed in the bone marrow

Effect levels

open allclose all
Dose descriptor:
NOEC
Effect level:
>= 300 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: male rat: reduced body weight at higher dose level
Dose descriptor:
NOEC
Effect level:
600 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: rabbit no adverse effects
Dose descriptor:
NOAEC
Effect level:
> 600 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: guinea pig no adverse effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Upon 6-month repeated dose inhalation of cyclohexene at dose levels of 0, 75, 150, 300 and 600 ppm (corresponding to 3.3, 6.7, 13.4 and 26.8 mmol/m³) with male rats, guinea pigs and rabbits, reduced body weights were reported for the high dose group of rats. No adverse effects were noted for guinea pigs or rabbits. The NOAEC was 300 ppm (13.4 mmol/m³) for rats.
Executive summary:

In a 6-month repeated dose inhalation study groups of male rats (20 per group), male guinea pigs (10 per group) and rabbits (6 per group) were exposed to cyclohexene in inhalation chambers for 6hr/day on 5 days/week. Dose levels were 75, 150, 300 and 600 ppm (corresponding to 3.3, 6.7, 13.4 and 26.7 mmol/m³) and appropriate control groups exposed to air in similar chambers. Exposure levels were analysed by gas chromatography. Body weights were recorded weekly, biochemistry, haematology and gross pathology of haemopoietic organs were carried out at termination. Based on a significantly reduced body weight in rats of the high dose group the NOAEC was 300 ppm (13.4 mmol/m³) for rats.