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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
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
No claim of GLP complaince or adherence with an official test guideline is made in the report. Comparison of the test methodology used to modern OECD guidelines highlights a number of significant discrepancies between the method employed in the test and the modern guideline, and the study report was considered generally not sufficiently detailed to consider the study data reliable. Note that as the material is classified as corrosive to skin (refer to dossier section 7.3), further acute toxicity testing cannot be justified, and so the result of this study is the only one available for acute toxicity testing by the dermal route. On this basis, this study was considered the key study, in spite of the poor reliability of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Animals: Sixteen albino rabbits of the New Zealand variety were obtained from the Skippack Farms and individually housed in suspended cages. All rabbits were fed Purina Rabbit Pellets and tap water on an ad libitum basis
Preparation and Treatment: Following a brief acclimation period, and prior to treatment, the backs of all rabbits were clipped free of fur; the animals were assigned to four treatment groups. Two rabbits in each group were abraded with a burred needle and two remained intact. Treatment consisted of a single dermal application of the 1,3-bis aminomethyl cyclohexane (1,3-BAC) to the skin. The test site was completely occluded with an impervious dam. After 24 hours, the wrapping was removed and the residue gently washed off.
Laboratory Observations
Animals were examined daily for abnormal behaviour or mortality. Skin reactions of erythema and edema were scored at 24 hours and daily thereafter for 14 days according to the method of Draize. Body weights were recorded on Days 0, 7, and 14. At termination or death, each animal was subjected to a gross examination of the viscera, except in cases of advanced autolysis of the tissue.

Note that according to OECD test guideline 402, skin should not be abraded and only animals with intact skin should be used. This guideline also recommends the use of at least 5 animals per dose level, unless a reason for the use of fewer animals can be justified. As half of the animals in each dose level had abraded skin, the results obtained from these animals should not be considered, as abrasion of the skin is likely to affect absorbtion of the test material, and as only two animals at each level had unabraded skin the sample size for each dose level is substantially smaller than the guideline recommendation. As a result of these aspects, this study must be consodered less reliable than one conducted according to the guideline.
GLP compliance:
not specified
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,3-Bis aminomethyl cyclohexane
- Substance type: clear colourless liquid
- Physical state: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: not specified
- Weight at study initiation: 2.77-3.90 kg
- Fasting period before study: not specified
- Housing: suspended cages
- Diet: ad libitum- Purina Rabbit Pellets
- Water: ad libitum

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: not specified
- Type of wrap if used: "impervious dam"

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Concentration (if solution): 1260, 1580, 2000, 2510 mg/kg
- Constant volume or concentration used: yes


Duration of exposure:
24 hours
Doses:
1260, 1580, 2000, 2510 mg/kg
No. of animals per sex per dose:
4 animals per dose, 2 with abraded skin
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 700 mg/kg bw
95% CL:
1 417 - 2 040
Mortality:
1260 mg/kg: no mortality; 1580 mg/kg: one death day 2, one death day 3; 2000 mg/kg:one death day 2, one death day 3; 2510 mg/kg: one death day 1, two death day 2, one death day 4.
Body weight:
Bodyweight tended to decrease in animals exposed above 1580 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information According to Directive 67/548/EEC. Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 was calculated to be 1700 mg/kg of body weight.* The 95% confidence limits are 1417 - 2040 mg/kg. 
Executive summary:

An acute dermal toxicity study was conducted by Huntingdon Research Centre, registered in Maryland, USA, on behalf of Sherwin-Williams Chemicals, Ohio, USA, to determine the acute toxic effects by dermal exposure of the test substance 1,3 -Bis Aminomethyl Cyclohexane.

Four groups of two rabbits with unabraded skin and two with abraded skin were exposed to the test material for a period of 24 hours, then the dressing removed and the exposure site washed. Dose levels assessed were 1260, 1580, 2000, and 2510 mg/kg. The exposure sites were observed for signs of skin reactions at 24 hours, and daily thereafter for 14 days. Animals were observed for clinical signs and mortality for 14 days.

After 24 hours of exposure, all rabbits (intact and abraded) exhibited severe erythema and edema. Within a few days, the edema subsided and the skin became "leathery" in appearance and to the touch. All surviving rabbits tended to lose weight during the 14-day post-exposure period. All rabbits died at the 2510 mg/kg level, 2/4 rabbits died at each of the 2000 and 1580 mg/kg levels, and all rabbits at the 1260 mg/kg level survived until the end of the 14 -day observation period.

The dermal LD50 was calculated to be 1700 mg/kg of body weight.