Cyclohexanone

Neurotoxicity

Description of key information

American Biogenic Corporation (1986) reported a 2-generation study with rats in doses ranging from 250 - 1000 ppm. The NOAEL for parental animals was 1000 ppm, for F1 animals was 500 ppm and for the F2 animals 500 ppm.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on neurotoxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

neurotoxicity: inhalation

Remarks:

2-generation study

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

This reproduction study was conducted to ascertain the potential effects of inhalation exposure to the test material vapour upon reproductive performance, growth, and development of 2 consecutive generations of rats including neurotoxicity.

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

see chapter Toxicity to reproduction

Route of administration:

inhalation: vapour

Details on exposure:

see chapter Toxicity to reproduction

Duration of treatment / exposure:

2 generations

Frequency of treatment:

6 h/d

Dose / conc.:

250 ppm (nominal)

Remarks:

approximately 1.02 mg/L

Dose / conc.:

500 ppm (nominal)

Remarks:

approximately 2.04 mg/L

Dose / conc.:

1 000 ppm (nominal)

Remarks:

(resp. 1400 ppm) approximately 4.1 mg/L

No. of animals per sex per dose:

see chapter Toxicity to reproduction

Control animals:

yes, concurrent no treatment

Observations and clinical examinations performed and frequency:

see chapter Toxicity to reproduction

Specific biochemical examinations:

see chapter Toxicity to reproduction

Neurobehavioural examinations performed and frequency:

Assessments for potential neurotoxicologic/neuropathologic effects were conducted pre-weaning and post-weaning in each F1a litter.

Sacrifice and (histo)pathology:

see chapter Toxicity to reproduction

Other examinations:

Neurotoxicity: brain (forebrain, center of cerebrum, midbrain, cerebellum and pons, medulla oblongata and Gasserian ganglia.

Statistics:

see chapter Toxicity to reproduction

Description (incidence and severity):

Further observations for developmental neurotoxicity study

Details on results (for developmental neurotoxicity):Evaluation of the specified tissues of the nervous system of untreated control and and 1000 ppm F1a progeny selected for neurotoxicologic testing did not reveal lesions in any of the tissues. Microscopic examinations of the eyes from the F1a progeny revealed lenticular vacuolation (vacuolation of a few outer cortical fibers in the lens) for 2/115 of the 500 ppm progeny and 3/114 of the 1000 ppm progeny.
For details see chapter Toxicity to Reproduction.

Conclusions:

The examining pathologist concluded that based on the low indicence and minimal nature of these changes, they were not treatment-related.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

4 100 mg/m³

Study duration:

subacute

Species:

rat

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Evaluation of the specified tissues of the nervous system of untreated control and 1000 ppm F1a progeny selected for neurotoxicity testing did not reveal lesions in any of the tissues. Microscopic examinations of the eyes from the F1a progeny revealed lenticular vacuolation (vacuolation of a few outer cortical fibers in the lens) for 2/115 of the 500 ppm progeny and 3/114 of the 1000 ppm progeny (ABC, 1986).