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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on GLP, study conducted prior to the advent of GLPs, detailed information on test conditions and results (i.e., individual animal scores for PDII) were not given in the publication.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1967

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
To investigate irritation, the substance was applied to the skin of a rabbit according the methods of Draize and Woodward in quantities of 0.1-0.5 ml for a duration of either 2 or 24 hours.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
technical grade epichlorohydrin (density 1.18 @ 20 C).

Test animals

Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
Test Animals: Rabbits, number tested, strain, sex, age, source and weight at study initiation, unknown

Test system

Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 ml or 0.1 to 0.2 ml
Duration of treatment / exposure:
24 hours (0.5 ml) or 2 hours (0.1 to 0.2 ml)
Observation period:
up to 30 days
Number of animals:
No data
Details on study design:
Administration/Exposure: Draize and Woodard, 1949; Area of Exposure: unknown; Examinations: Draize and Woodard, 1949

Results and discussion

In vivo

Results
Irritation parameter:
other: necrosis
Basis:
mean
Time point:
other: 24 hr
Score:
>= 3
Reversibility:
not fully reversible within: 30 days
Remarks on result:
other: reversibility based on histopathologic examination
Irritant / corrosive response data:
Epichlorohydrin applied on the skin in quantities of 0.5 ml for 24 hours caused appearance of a lesion presenting as a central zone of coagulation necrosis surrounded by hard swelling also affecting the superficial layers of the dermis. At the periphery of the lesion was a zone of erythema of various intensities with numerous petechial hemorrhages covering the application area. The application of smaller quantities, 0.1 to 0.2 ml, for a shorter period, 2 hours, resulted in the appearance of a similar lesion but of less intensity and reduced dimensions. In all cases after two to three days the zones of necrosis and erythema were covered by eschar which healed slowly (after 30 days for the 0.5 ml application). Following recovery the macroscopic appearance of the skin was normal.
Other effects:
Epichlorohydrin, applied to the skin in 0.5 ml aliquots for 24 hours, caused the appearance of a lesion presenting a central zone of necrosis and scabbing, surrounded by firm edema, present also in the underlying superficial dermis. At the edge the lesion had a zone of erythema of varying intensity, with numerous petechial hemorrhages, extending beyond the area in contact with epichlorohydrin. Application of smaller quantities, 0.1-0.2 ml, for a shorter period, 2 hours, resulted in the development of similar lesions, but much reduced in intensity and size. In all cases, after 2-3 days, the zones of necrosis and erythema had resolved to the point of eschar formation which was persistent (30 days after the 0.5 ml application), but in which healing proceeded normally macroscopically.

Any other information on results incl. tables

Doses of 0.1 -0.2 ml applied to the skin for 2 hours was necrotic with healing noted histopathologically. Higher doses for 24 hours resulted in a more severe response.

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test material was corrosive to the skin of rabbits.
Executive summary:

To investigate irritation, the substance was applied to the skin of a rabbit according the methods of Draize and Woodward in quantities of 0.1-0.5 ml for a duration of either 2 or 24 hours. Epichlorohydrin, applied to the skin in 0.5 ml aliquots for 24 hours, caused the appearance of a lesion presenting a central zone of necrosis and scabbing, surrounded by firm edema, present also in the underlying superficial dermis. At the edge the lesion had a zone of erythema of varying intensity, with numerous petechial hemorrhages, extending beyond the area in contact with epichlorohydrin. Application of smaller quantities, 0.1-0.2 ml, for a shorter period, 2 hours, resulted in the development of similar lesions, but much reduced in intensity and size. In all cases, after 2-3 days, the zones of necrosis and erythema had resolved to the point of eschar formation which was persistent (30 days after the 0.5 ml application), but in which healing proceeded normally macroscopically.