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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not reported
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies

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 application
Author:
Treon JF, Crutchfield Jr WE & Kitzmiller KV
Year:
1943
Bibliographic source:
J. Ind. Hyg. Toxicol. 25: 199-214

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was reported in 1943 before GLP and OECD guidelines were introduced. Rodent exploratory toxicity study on single animals per dose to determine the minimum lethal dose.
GLP compliance:
no
Test type:
other: cutaneous application
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Supplier: commercial product, not specified.
Specially prepared and of high purity.

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Anterior abdominal wall, clipped
- % coverage: Approximately 24 square inches
- Type of wrap if used: None

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, washed with soap and water and the skin dried
- Time after start of exposure: 20 minutes after the last dose for surviving animals

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 35, 65 and 130 mL for the 12 400, 22 700 and 45 600 mg/kg dose levels, respectively.
Duration of exposure:
The test material was applied in 5 mL aliquots at 20 minute intervals, therefore the exposure periods were assumed to be approximately 2 hours, 4 hours and 8 hours and 20 minutes for the 12 400, 22 700 and 45 600 mg/kg dose levels, respectively. The skin was kept moist for the entire period.
Doses:
12 400, 22 700 and 45 600 mg/kg
No. of animals per sex per dose:
1 animal per dose
Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: No data
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No
- Other experimental details: To avoid the possibility of inhalation, the animals were kept in a well ventilated hood with their heads pointed into the airstream.

Results and discussion

Effect levels
Key result
Sex:
not specified
Dose descriptor:
LDLo
Effect level:
12 400 - 22 700 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The minimum lethal dose for rabbits by cutaneous application lies between 12 400 and 22 700 mg/kg
Mortality:
The animals receiving the two higher doses died.
Clinical signs:
Marked hypothermia, convulsive movements and narcosis resulted from cutaneous application. Rabbit C73, to which the smallest dose was given, was only slightly anaesthetised for about 1 and a half hours, near the end of the experiment. The rectal temperature, which was only slightly reduced by the experimental procedure, began to rise about 2 hours later. No convulsive movements were noted and the rabbit survived. The other two rabbits (C64 and C65) showed a considerable drop in body temperature and died in 7 to 8 and a half hours. They became slightly anaesthetised in about 2 hours and deeply so in another hour. The animal that received the largest dose (C65) exhibited involuntary jerking and twitching of the forelegs and chest muscles during the three hours preceding death. In all these rabbits there was slight local erythema of the skin and considerable lacrimation. The lacrimation was considered to be due to transport of the compound by the blood stream and not to the direct action of vapour on the eyes as the animals were kept hooded to avoid inhalation of vapour.
Other findings:
Application caused death following a marked decrease in body temperature, demonstrating the permeability of the skin for the test material. Death is not ascribed solely to the hypothermia; however, this may increase the susceptibility of the animals to the toxic action of the substance.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
Under the conditions of this study, the minimum lethal dose of the test material when administered cutaneously to rabbits lies between 12 400 and 22 700 mg/kg.
Executive summary:

The toxicity of the test material was investigated via the dermal route. The study was reported in 1943 before GLP and OECD guidelines were introduced and a non-rodent exploratory toxicity study was carried out on single animals per dose to determine the minimum lethal dose. The test material was applied to the clipped anterior abdominal wall (approximately 24 square inches) of one rabbit per dose level. The three dose levels were 12 400, 22 700 and 45 600 mg/kg. The test material was applied in 5 mL aliquots at 20 minute intervals, therefore the exposure periods were assumed to be approximately 2 hours, 4 hours and 8 hours and 20 minutes for the 12 400, 22 700 and 45 600 mg/kg dose levels, respectively (35, 65 and 130 mL). The skin was kept moist for the entire period. 20 minutes after the last dose for surviving animals the skin was washed and dried. To avoid the possibility of inhalation, the animals were kept in a well ventilated hood with their heads pointed into the airstream.

The animals receiving the two higher doses died. Marked hypothermia, convulsive movements and narcosis resulted from cutaneous application. Rabbit C73, to which the smallest dose was given, was only slightly anaesthetised for about 1 and a half hours, near the end of the experiment. The rectal temperature, which was only slightly reduced by the experimental procedure, began to rise about 2 hours later. No convulsive movements were noted and the rabbit survived. The other two rabbits (C64 and C65) showed a considerable drop in body temperature and died in 7 to 8 and a half hours. They became slightly anaesthetised in about 2 hours and deeply so in another hour. The animal that received the largest dose (C65) exhibited involuntary jerking and twitching of the forelegs and chest muscles during the three hours preceding death. In all these rabbits there was slight local erythema of the skin and considerable lacrimation. The lacrimation was considered to be due to transport of the compound by the blood stream and not to the direct action of vapour on the eyes as the animals were kept hooded to avoid inhalation of vapour.

Under the conditions of this study, the minimum lethal dose of the test material when administered cutaneously to rabbits lies between 12 400 and 22 700 mg/kg.