Cyclohexanemethanol, 4-(1-methylethyl)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

OECD guideline equivalent study with deviations from current methodology. Considered sufficiently reliable for the purpose of hazard assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

purity, solubility, melting/boiling point, pH of the test material not reported; sex, acclimatization period, randomization not reported; fur was removed from ventral surface; skin abraded; shaved area not measured.

GLP compliance:

no

Remarks:

Study pre-dates GLP

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

cis-4-(isopropyl)cyclohexanemethanol

EC Number:

237-539-8

EC Name:

cis-4-(isopropyl)cyclohexanemethanol

Cas Number:

13828-37-0

Molecular formula:

C10H20O

IUPAC Name:

cis-(4-propan-2-ylcyclohexyl)methanol

Constituent 2

Reference substance name:

trans-(4-propan-2-ylcyclohexyl)methanol

Cas Number:

13674-19-6

Molecular formula:

C10H20O

IUPAC Name:

trans-(4-propan-2-ylcyclohexyl)methanol

Test material form:

not specified

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: New England Rabbitry Supply Inc.
- Age at study initiation: no data
- Fasting period before study: 24 hours
- Housing: no data
- Diet :ad libitum
- water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Hair was removed from the ventral surface of the four animals and shaved areas were abraded. Note that the report description of methods and data values clearly show 6 animals in the test group but describes shaving and abrasion of the test site for 4 animals. The status of the remaining 2 animals is unclear and the report does not provide information on these remaining animals. Therefore it seems likely that all 6 animals had shaved and abraded skin and the statement regarding just 4 was erroneous.

TEST SITE
- Area of exposure: ventral surface
- % coverage: no data
- Type of wrap if used: gauze bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Constant concentration used: 100% test material

VEHICLE: no

Duration of exposure:

24 hours

Doses:

2,000 mg/kg

No. of animals per sex per dose:

6 per group

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily observations for signs of dermal irritation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (recorded 2 and 4 hours post-application and daily thereafter) and body weight (recorded prior to application, 7 days post-application, and at termination).

Statistics:

not required

Results and discussion

Preliminary study:

not applicable

Effect levels

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 mg/kg bw

Based on:

test mat.

Mortality:

One animal died on Day 8 (post-application).

Clinical signs:

other: At 24 hours post-application, all animals were noted to be lethargic and these observations persisted until Day 4 post-application. There also was a decrease in food and water consumption observed from Day 1 to Day 5 post-application.

Gross pathology:

At necropsy, findings in the premature decedent were limited to an enlarged gall bladder. Macroscopic examinations of the remaining animals did not reveal any adverse findings.

Other findings:

The test compound induced dermal irritation (erythema and edema) in the treated animals; see Table 1 and Table 2 below.

Any other information on results incl. tables

Table 1       Erythema Scores of Test Compound 0778/3 in the Rabbit*

Animal No.	19	20	21	22	23	24
Day No.
1	2	2	1	2	2	1
2	4	4	2	3	2	3
3	4	4	2	3	2	3
4	4	4	2	3	2	3
5	4	4	2	3	2	3
6	4	4	1	3	2	3
7	4	4	1	3	2	3
8	3	3	0	-	1	3
9	3	3	0	-	1	2
10	2	2	0	-	0	2
11	2	2	0	-	0	2
12	1	1	0	-	0	1
13	1	1	0	-	0	1
14	1	0	0	-	0	0

* The degree of dermal irritation was scored according to the Draize method.

Table 2       Edema Scores of Test Compound 0778/3 in the Rabbit*

Animal No.	19	20	21	22	23	24
Day No.
1	2	2	0	1	1	0
2	3	3	0	1	2	2
3	3	3	0	1	2	2
4	4	4	0	1	2	2
5	3	3	0	0	1	1
6	2	2	0	0	1	1
7	0	0	0	0	0	0
8	0	0	0	-	0	0
9	0	0	0	-	0	0
10	0	0	0	-	0	0
11	0	0	0	-	0	0
12	0	0	0	-	0	0
13	0	0	0	-	0	0
14	0	0	0	-	0	0

  * The degree of dermal irritation was scored according to the Draize method.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 dermal, rabbit > 2,000 mg/kg

Executive summary:

The dermal LD50 of the test compound was determined to be greater than 2,000 mg/kg body weight in this study. The one mortality noted during this study was considered unrelated to the application of the test compound as similar gross pathological findings (enlarged gall bladder) were not observed in the remaining animals at necropsy. While dermal irritation (erythema and/or edema) was observed in all animals, it should be noted that the test compound was applied to the ventral surface of the animals on shaved and abraded skin (a deviation according to OECD Guideline 402). It is worth noting that there is an apparent inaccuracy in the study report. The report states that there were six animals in the treatment group while a subsequent sentence states that "the four" animals were shaved and had shaved skin abraded. As the remainder of the report does not differentiate between animals with shaved/abraded skin and any that might have been unshaven/unabraded, it is assumed that all animals were in fact shaved and their shaved skin was abraded. Abrading the skin could have altered its permeability. It also was unclear in the study report whether residual test substance was removed (with water or an appropriate solvent) at the end of the 24-hour exposure period. Despite the deviations noted in the study design, the LD50 is considered not to be affected.