Methylcyclohexane

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Only limited information given.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

The physiological response of rabbits to cyclohexane, methylcyclohexane, and certain derivatives of these compounds. I Oral Administration and Cutaneous Administration

Author:

Treon, J. et al.

Year:

1943

Bibliographic source:

J. Indust. Hygiene Toxicol. 25(6), 199-214

Materials and methods

Principles of method if other than guideline:

Subacute (6-day) dermal toxicity study in one rabbit

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methylcyclohexane

EC Number:

203-624-3

EC Name:

Methylcyclohexane

Cas Number:

108-87-2

Molecular formula:

C7H14

IUPAC Name:

methylcyclohexane

Details on test material:

- Name of test material (as cited in study report): methylcyclohexane
- Substance type: pure substance
- Physical state: colourless liquid
- Analytical purity: 97%
- Impurities (identity and concentrations): toluene, 3%
- Specific gravity: 0.767

Test animals

Species:

rabbit

Strain:

other: White

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: ca. 3.185 kg (calculated from the reported results)

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: approx. 24 square inches (corresponding to ca. 155 cm²) of the anterior abdominal wall
- Time intervals for shavings or clipplings: the hair of the animal was closely clipped prior to the first application.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test material was removed by washing with soap and water.
- Time after start of exposure: 1 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 60 mL (twelve 5 mL portions at 5 min intervals)
- Constant volume or concentration used: yes

USE OF RESTRAINERS FOR PREVENTING INHALATION: yes

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

6 days

Frequency of treatment:

daily, 12 applications within 1 h

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
60 mL per 24 square inches per day (specific gravity 0.767)
Basis:
other: reported data

Doses / concentrations 2

Remarks:

Doses / Concentrations:
ca. 300 mg/cm²/day
Basis:
nominal per unit area

Doses / concentrations 3

Remarks:

Doses / Concentrations:
ca. 14450 mg/kg bw/day
Basis:
nominal per unit body weight

No. of animals per sex per dose:

1 animal

Control animals:

no

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DERMAL IRRITATION: Yes
- Time schedule for examinations: daily

BODY WEIGHT: Yes
- Time schedule for examinations: presumably daily (not specified)

RECTAL TEMPERATURE: Yes
- Time schedule for examinations: presumably daily (not specified)

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

slight hypothermia, no mortality

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

local irritation, skin hardening, thickening and ulceration

Mortality:

mortality observed, treatment-related

Description (incidence):

slight hypothermia, no mortality

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

slight loss in weight

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
The treated animal did not die and slight hypothermia (not further specified) was observed during the 6-day study period.

DERMAL IRRITATION
Repeated application of methylcyclohexane to the skin of a rabbit induced local irritation and thickening. The irritation appeared on the second day and increased with succesive treatments. Hardening of the skin, thickening and ulceration appeared later and the experiment was terminated after the 6th day.

BODY WEIGHT AND WEIGHT GAIN
The treated animal showed a slight loss in weight (not further specified) during the 6 day-study period. The loss in body weight was regained within 2 days.

Effect levels

1

Dose descriptor:

conc. level:

Effect level:

300 mg/cm² per day (nominal)

Based on:

test mat.

Sex:

not specified

2

Dose descriptor:

dose level:

Effect level:

14 450 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: succesively increasing local irritation; hardening of the skin, thickening and ulceration appearing within 6 days; slight hypothermia and loss in weight

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The authors reported the "range of lethal dosage" to be > 86.7 g/kg bw.

This is evidently a cumulated dose calculated over the 6 -day study period:

60 mL per day = 46.02 g per day (based on a specific gravity of 0.767)

46.02 g x 6 days = 276.12 g

A cumulated dose of 86.7 g/kg bw is thus calculated assuming a body weight of ca. 3.185 kg.

Applicant's summary and conclusion

Conclusions:

Methylcyclohexane was applied to the clipped skin of one rabbit in twelve 5 ml portions at 5 min intervals within 1 h, after which the material was removed by washing with soap and water. This uncovered skin procedure was done on 6 consecutive days. Based on the reported total amount of test substance applied daily (60 mL), the specific gravity (0.767) and the animal body weight (3.185 kg), the applied dose was roughly equivalent to 14450 mg/kg bw/day. The test substance was applied on a surface of approximately 24 square inches (corresponding to ca. 155 cm²). Thus, the local dose was about 300 mg/cm²/day.
Slight hypothermia and a slight loss in body weight (no further details given) were observed in the treated animal during the 6-day study period. The loss in body weight was regained within 2 days. Repeated application of methylcyclohexane to the skin of a rabbit induced local irritation and thickening. The irritation appeared on the second day and increased with successive treatments. Hardening of the skin, thickening and ulceration appeared later and the experiment was terminated after the 6th day.

Due to deficiencies in study design (one animal, one dose level, 6-day exposure) and limited documentation, the results of this study are not fully sufficient for assessment of toxicity after repeated dermal exposure, not adequate for the purpose of classification and therefore inconclusive.

CLP: inconclusive
DSD: inconclusive