Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
yes
Remarks:
(Extention of the exposure period, additional repeated dose group for females and a 4-week recovery period (males))
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Cyclohexanol
EC Number:
203-630-6
EC Name:
Cyclohexanol
Cas Number:
108-93-0
Molecular formula:
C6H12O
IUPAC Name:
cyclohexanol

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Males: 16 wks (10 weeks premating)
Females: 13 wks
(post exposure observation time: 4 weeks)
Frequency of treatment:
6 hours/day, 5 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
0 ppm
Dose / conc.:
50 ppm
Remarks:
0.21 mg/L nominal conc.
Dose / conc.:
150 ppm
Remarks:
0.61 mg/L nominal conc.
Dose / conc.:
450 ppm
Remarks:
After 10 weeks exposure, the level was reduced to 400 ppm due to slight mortality and the perceived additional stress of mating (females).
1.84/1.64 mg/L nominal conc.
No. of animals per sex per dose:
15 (10 animals/sex/dose in the main group; 5 animals/sex/dose in the recovery group)
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: no data
- Post-exposure recovery period in satellite groups: 4 weeks, 5 rats/sex/dose

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

OPHTHALMOSCOPIC EXAMINATION: Yes

HAEMATOLOGY: Yes
- Time schedule for collection: After 5 weeks (5 animals/sex/group), 13 weeks (10/females/group), 18 weeks (10 males/group), and after the 4-week recovery period (5 animals/sex/group) were selected for blood collection

CLINICAL CHEMISTRY: Yes
- Time schedule for collection: After 5 weeks (5 animals/sex/group), 13 weeks (10/females/group), 18 weeks (10 males/group), and after the 4-week recovery period (5 animals/sex/group) were selected for blood collection

URINALYSIS: Yes

NEUROBEHAVIOURAL EXAMINATION: Yes
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Complete necropsies were performed on all rats and specific organs and tissues were weighed and examined microscopically.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
In the weekly detailed clinical observations, no compound related effects were seen. However, in observations conducted immediately post-exposure, adverse clinical signs such as decreased activity and prostration were seen in a few animals (both sexes) in the 450/400 ppm exposure group. Please also refer to Table 1.
Mortality:
mortality observed, non-treatment-related
Description (incidence):
Single males were found dead at 450 ppm on Days 37,38 and 60 of the study. A single female rat was euthanized in extremis on Day 17. One female was found dead on Day 31. No cause of death could be determined.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Haematological findings:
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Urinalysis findings:
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No compound related effects were seen.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEC
Remarks:
(systemic toxicity)
Effect level:
0.61 mg/L air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
Dose descriptor:
LOAEC
Effect level:
1.64 mg/L air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality

Target system / organ toxicity

Key result
Critical effects observed:
no

Any other information on results incl. tables

Table 1: Mortality

 

Test group 0

0 ppm

(0 mg/L)

Test group 1

50 ppm#

(0.21 mg/L)

Test group 2

150 ppm

(0.610 mg/L)

Test group 3

450/400 ppm+

(1.84/1.64 mg/L)

Males

0/15

1/15

0/15

3/15

Females

0/15

1/15

0/15

2/15

#50 ppm group: incidentally, one male died during blood collection on Day 126 and one female was found dead on Day 32.

+450/400 ppm: 3 males were found dead on Days 37, 38 and 60; 1 female was found dead on Day 31 and 1 female was euthanizedin extremison Day 17. Clinically decreased activity, prostration, and difficult breathing were seen prior to death.

Applicant's summary and conclusion