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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is in compliance with OECD guidelines, as well as U.S. EPA/FIFRA, U.S. EPA/TSCA, and EU guidelines.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is in compliance with OECD guidelines, as well as U.S. EPA/FIFRA, U.S. EPA/TSCA, and EU guidelines.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Qualifier:
according to
Guideline:
other: U.S. EPA/FIFRA Guidelines §82-4
Qualifier:
according to
Guideline:
EPA OTS 798.2450 (90-Day Inhalation Toxicity)
Qualifier:
according to
Guideline:
other: U.S. EPA/TSCA Guidelines 40 CFR §798.6059, and §798.6059, 798.6200, 798.6400
Qualifier:
according to
Guideline:
other: EU Guideline 87/302/EEC
GLP compliance:
not specified
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
not reported
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: no data
Details on inhalation exposure:
not reported
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Concentrations were determined by gas chromatography.
Duration of treatment / exposure:
Rats were exposed to vapours of cyclopentane for 90 days.
Frequency of treatment:
6 hours per workday
Remarks:
Doses / Concentrations:
5, 10, 30 (pure), 30 (technical) mg/L
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5.0±0.2, 10.0±0.3, 29.8±1.5 (pure), 29.8±1.8 mg/L
Basis:
analytical conc.
No. of animals per sex per dose:
15 males and 15 females per dose group
Control animals:
yes, concurrent no treatment
Details on study design:
not reported
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: yes
- Time schedule: General observation were made twice on weekdays and once on weekends and holidays.
- Cage side observations were not included in a table.

DETAILED CLINICAL OBSERVATIONS: yes
- Time schedule: Clinical examinations were made once per weekday during preflow and the on the day following exposure.

BODY WEIGHT: yes
- Time schedule for examinations: measured weekly

FOOD CONSUMPTION: not reported

FOOD EFFICIENCY: not reported

WATER CONSUMPTION: not reported
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: yes
- Time schedule for examinations: Examinations were carried out prior to and following exposure.
- Dose groups that were examined: not reported

HAEMATOLOGY: Yes / No / No data: yes
- Time schedule for collection of blood: Examinations of numerous parameters were preformed at the end of the exposure period.
- Anaesthetic used for blood collection: not reported
- Animals fasted: not reported
- How many animals: 10 males and 10 females

CLINICAL CHEMISTRY: yes
- Time schedule for collection of blood: Examinations of numerous parameters were preformed at the end of the exposure period.
- Animals fasted: not reported
- How many animals: 10 males and 10 females

URINALYSIS: not reported

NEUROBEHAVIOURAL EXAMINATION: yes (neurofunctional tests)
- Time schedule for examinations: performed three times during the exposure period (approximately once per month)
- Dose groups that were examined: not reported
- Battery of functions tested: not reported
Sacrifice and pathology:
A complete necropsy was performed on 15 animals per sex, which included weighing of selected organs and gross pathological evaluation.

5 animals per sex, of those subject to neurofunctional testing, were sacrificed by perfusion fixation and examined neuropathologically.
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:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
No abnormalities were detected during clinical, neurofunctional, and clinico-pathological examinations in any of the test groups. No changes were found during necropsy or in the histo- and neuropathological examinations.
Key result
Dose descriptor:
NOAEC
Effect level:
30 mg/L air
Basis for effect level:
other: Equivalent to 30,000 mg/m3; 29.8 ± 1.5 (pure) or 29.8±1.8 (technical) mg/L air was the actual concentration
Critical effects observed:
not specified
Conclusions:
Subchronic inhalation exposure up to 30 mg/L of cyclopentane vapour (i.e, technical grade or high purity) did not cause a substance-related toxic effect. The NOAEC is 30 mg/L under the conditions of this study.
Executive summary:

Fifteen male and 15 female Wistar rats per test group were exposed to cyclopentane vapour (pure) at concentrations of 5, 10, 30 mg/L and cyclopentane vapour (technical grade) at a concentration of 30 mg/L for 6 hours per weekday for 90 days. A concurrent control group was exposed to clean air. General observation were performed twice during weekdays and once during weekends and holidays. Clinical examinations were performed once every weekday and on the day following exposure. Neurofunctional test were performed in 10 animals per sex, once before the exposure period and three times during the exposure period. A hematological and clinicochemical examination was performed in 10 animals per sex at the end of the exposure period. A complete necropsy was performed on 10 animals per sex, which included weighing of selected organs and gross pathological evaluation. 5 animals per sex, of those subject to neurofunctional testing, were sacrificed by perfusion fixation and examined neuropathologically. Subchronic inhalation exposure to up to 30 mg/L of cyclopentane vapour (i.e., technical grade or high purity) did not cause a substance related toxic effect. The NOAEC is 30 mg/L under the conditions of this study.

This study was given a Kilimsh score of 1, reliable without restriction. The study had minor discrepancies that are listed in the overall remarks/attachments comment box in this robust summary.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Qualifier:
according to
Guideline:
other: U.S. EPA/FIFRA Guidelines §82-4
Qualifier:
according to
Guideline:
EPA OTS 798.2450 (90-Day Inhalation Toxicity)
Qualifier:
according to
Guideline:
other: U.S. EPA/TSCA Guidelines 40 CFR §798.6059, and §798.6059, 798.6200, 798.6400
Qualifier:
according to
Guideline:
other: EU Guideline 87/302/EEC
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): cyclopentane
- Substance type: C5 aliphatics
- Physical state: gas
- Analytical purity: Test groups were exposed to pure cyclopentane at concentrations of 5, 10, and 30 mg/L. One test group was exposed to technical grade (i.e., approximately 78% cyclopentane) at a concentration of 30 mg/L.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
not reported

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: no data
Details on inhalation exposure:
not reported
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Concentrations were determined by gas chromatography.
Duration of treatment / exposure:
Rats were exposed to vapours of cyclopentane for 90 days.
Frequency of treatment:
6 hours per workday
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
5, 10, 30 (pure), 30 (technical) mg/L
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5.0±0.2, 10.0±0.3, 29.8±1.5 (pure), 29.8±1.8 mg/L
Basis:
analytical conc.
No. of animals per sex per dose:
15 males and 15 females per dose group
Control animals:
yes, concurrent no treatment
Details on study design:
not reported

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: yes
- Time schedule: General observation were made twice on weekdays and once on weekends and holidays.
- Cage side observations were not included in a table.

DETAILED CLINICAL OBSERVATIONS: yes
- Time schedule: Clinical examinations were made once per weekday during preflow and the on the day following exposure.

BODY WEIGHT: yes
- Time schedule for examinations: measured weekly

FOOD CONSUMPTION: not reported

FOOD EFFICIENCY: not reported

WATER CONSUMPTION: not reported
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: yes
- Time schedule for examinations: Examinations were carried out prior to and following exposure.
- Dose groups that were examined: not reported

HAEMATOLOGY: Yes / No / No data: yes
- Time schedule for collection of blood: Examinations of numerous parameters were preformed at the end of the exposure period.
- Anaesthetic used for blood collection: not reported
- Animals fasted: not reported
- How many animals: 10 males and 10 females

CLINICAL CHEMISTRY: yes
- Time schedule for collection of blood: Examinations of numerous parameters were preformed at the end of the exposure period.
- Animals fasted: not reported
- How many animals: 10 males and 10 females

URINALYSIS: not reported

NEUROBEHAVIOURAL EXAMINATION: yes (neurofunctional tests)
- Time schedule for examinations: performed three times during the exposure period (approximately once per month)
- Dose groups that were examined: not reported
- Battery of functions tested: not reported
Sacrifice and pathology:
A complete necropsy was performed on 15 animals per sex, which included weighing of selected organs and gross pathological evaluation.

5 animals per sex, of those subject to neurofunctional testing, were sacrificed by perfusion fixation and examined neuropathologically.

Results and discussion

Results of examinations

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:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
No abnormalities were detected during clinical, neurofunctional, and clinico-pathological examinations in any of the test groups. No changes were found during necropsy or in the histo- and neuropathological examinations.

Effect levels

Key result
Dose descriptor:
NOAEC
Effect level:
30 mg/L air
Basis for effect level:
other: Equivalent to 30,000 mg/m3; 29.8 ± 1.5 (pure) or 29.8±1.8 (technical) mg/L air was the actual concentration

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Subchronic inhalation exposure up to 30 mg/L of cyclopentane vapour (i.e, technical grade or high purity) did not cause a substance-related toxic effect. The NOAEC is 30 mg/L under the conditions of this study.
Executive summary:

Fifteen male and 15 female Wistar rats per test group were exposed to cyclopentane vapour (pure) at concentrations of 5, 10, 30 mg/L and cyclopentane vapour (technical grade) at a concentration of 30 mg/L for 6 hours per weekday for 90 days. A concurrent control group was exposed to clean air. General observation were performed twice during weekdays and once during weekends and holidays. Clinical examinations were performed once every weekday and on the day following exposure. Neurofunctional test were performed in 10 animals per sex, once before the exposure period and three times during the exposure period. A hematological and clinicochemical examination was performed in 10 animals per sex at the end of the exposure period. A complete necropsy was performed on 10 animals per sex, which included weighing of selected organs and gross pathological evaluation. 5 animals per sex, of those subject to neurofunctional testing, were sacrificed by perfusion fixation and examined neuropathologically. Subchronic inhalation exposure to up to 30 mg/L of cyclopentane vapour (i.e., technical grade or high purity) did not cause a substance related toxic effect. The NOAEC is 30 mg/L under the conditions of this study.

This study was given a Kilimsh score of 1, reliable without restriction. The study had minor discrepancies that are listed in the overall remarks/attachments comment box in this robust summary.