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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:
key study
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results. Study does not meet guideline requirements for minimum number of animals/dose level. .

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The dermal LD50 was examined using epichlorohydrin, neat, or diluted with propylene chloride with rabbits. Animals were observed until they died or regained pre-treatment weight.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
>99% purity

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Weight at Study Initiation: 2.43-3.50 kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Dosed undiluted and as a 20% solution in propylene glycol
Details on dermal exposure:
Single dose

Area Covered: Unknown

Occlusion: Impervious cuff held in place with cloth bandage taped to hair

Removal of Test Material: Washing with soap and water 24 hours post-dosing

Maximum Volume Administered: 2.38 ml

Post-Dose Observation Period: 2 weeks

Duration of exposure:
24 hours
Doses:
Undiluted: 100, 200, 465, 795 mg/kg
20% solution in propylene glycol: 252, 500, 630 or 795 mg/kg
No. of animals per sex per dose:
2/sex/dose
Control animals:
no
Details on study design:
Approximately 24 hours prior to dosing, the hair was removed from the trunk of 2 laboratory white rabbits/dose level with electric clippers. The test material was applied at 100, 200, 465, or 795 mg/kg body weight under an impervious cuff held in place with a cloth bandage taped to the hair.
Following application the animals were returned to holding cages and allowed to eat and drink ad libitum. Following a 24-hour exposure period, the cuffs were removed and the skins washed with soap and water. The animals were observed during and after exposure and weighed at intervals up to two weeks post-application. The animals were then submitted for necropsy examination at death or at scheduled study termination.
Statistics:
LD50 calculation method not specified

Results and discussion

Preliminary study:
not applicable
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
515 mg/kg bw
Remarks on result:
other: Undiluted
Sex:
male/female
Dose descriptor:
LD50
Effect level:
250 - 500 mg/kg bw
Remarks on result:
other: 20% solution in propylene glycol
Mortality:
Undiluted

# Dead/# Treated
Dose Male Female
(mg/kg)
100 0/2 0/2
200 0/2 0/2
465 1/2 0/2 Found dead 24 hours post-dosing
795 2/2 2/2 Found dead 24 hours post-dosing

20% solution in propylene glycol

# Dead/# Treated
Dose Male Female
(mg/kg)
252 0/2 0/2
500 2/2 2/2 Found dead 24-48 hours post-dosing
630 - 2/2 Found dead 24 hours post-dosing
795 - 2/2 Found dead 24 hours post-dosing
Clinical signs:
Severe redness and swelling and slight necrosis were observed when the cuffs were removed after the 24-hour exposure to either test material.
Body weight:
Survivors dosed at 200 mg/kg and higher of either solution required 3 to 6 weeks to regain pre-treatment weight; animals dosed at 100 mg/kg required 2 to 3 weeks to regain pre-treatment weight.
Gross pathology:
no data
Other findings:
no additional information available

Any other information on results incl. tables

Two male and two female rabbits per dose level were exposed to undiluted epichlorohydrin or a 20% solution of epichlorohydrin in propylene glycol in acute percutaneous absorption tests. The LD50 for undiluted epichlorohydrin was 515 mg/kg and for the 20% solution in propylene glycol was between 250 and 500 mg/kg epichlorohydrin. Propylene glycol may enhance the toxicity of epichlorohydrin by this route as in the previous Dow Test.

Survivors dosed at 200 mg/kg and higher of either solution required 3 to 6 weeks to regain pre-treatment weight; animals dosed at 100 mg/kg required 2 to 3 weeks to regain pre-treatment weight. Severe redness and swelling and slight necrosis were observed when the cuffs were removed after the 24-hour exposure to either test material.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Based on the results of the study LD50 for undiluted epichlorohydrin was 515 mg/kg and for the 20% solution in propylene glycol was between 250 and 500 mg/kg.
Executive summary:

Two male and two female rabbits per dose level were exposed to undiluted epichlorohydrin or a 20% solution of epichlorohydrin in propylene glycol in acute percutaneous absorption tests. The LD50 for undiluted epichlorohydrin was 515 mg/kg and for the 20% solution in propylene glycol was between 250 and 500 mg/kg epichlorohydrin. Propylene glycol may enhance the toxicity of epichlorohydrin by this route as in the previous Dow Test.

Survivors dosed at 200 mg/kg and higher of either solution required 3 to 6 weeks to regain pre-treatment weight; animals dosed at 100 mg/kg required 2 to 3 weeks to regain pre-treatment weight. Severe redness and swelling and slight necrosis were observed when the cuffs were removed after the 24-hour exposure to either test material.