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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Clear liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hours prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact. The dose was based on the sample weight as calculated from the specific gravity. The test article was applied to the prepared dermal site, one time, by syringe type applicator on a g/kg basis. The test site was covered with a gauze patch, secured with non-irritating tape and gentle pressure was applied to the gauze to aid the distribution of the test article over the area. The torso was wrapped with plastic which was secured with non-irritating tape. At 24 hours, the patches were removed. The residual test article was gently washed off with distilled water prior to dermal observations.
Duration of exposure:
24 hours
Doses:
1000, 1600, 2000, 2500 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The test sites were scored for dermal irritation at 24 hours post dose and on days 7 and 14 using the numerical Draize scale. Additional signs were described. The animals were observed 1, 2 and 4 hours post dose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for 14 days for mortality. Body weights were recorded pretest, weekly and at death or termination. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.
Statistics:
The LD 50, 95% Confidence Limits, dose response curve and slope were calculated by the method of
Litchfield, J.T., Jr., & Wilcoxon, F., JPET 96:99, 1949.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 700 mg/kg bw
Based on:
test mat.
95% CL:
> 1 300 - < 2 200
Sex:
female
Dose descriptor:
LD50
Effect level:
1 800 mg/kg bw
Based on:
test mat.
95% CL:
> 1 300 - < 2 500
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 700 mg/kg bw
Based on:
test mat.
95% CL:
> 1 300 - < 2 200
Mortality:
1000 mg/kg bw: 0/5 males, 0/5 females
1600 mg/kg bw: 3/5 males, 3/5 females
2000 mg/kg bw: 3/5 males, 2/5 females
2500 mg/kg bw: 4/5 males, 4/5 females
Clinical signs:
The deaths occurred by day 4 and were preceded by physical signs of diarrhea, lethargy, ptosis, dyspnea, negative righting reflex, ataxia, few feces, yellow nasal discharge, red discharge and soiling of the anogenital area, convulsions and mucoid diarrhea. Necropsy of the dead animals revealed abnormalities of the lungs, liver, spleen, pleural cavity, eyes, treated skin, kidneys, heart and gastrointestinal tract, as well as soiling of the anogenital area, wetness of the nose/mouth area, wetness of the anogenital area and red staining of the anogenital area.
Physical signs noted in survivors included lethargy, ptosis, yellow nasal discharge, diarrhea, ataxia, dyspnea, few feces, emaciation, soiling of the anogenital area, red discharge, ocular discharge, red staining of the anogenital and mucoid diarrhea.
Body weight:
Body weight changes of survivors were generally normal, although instances of weight loss were noted in survivors of all groups.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The LD50 was determined to be 1700 mg/kg bw (males/females combined)
Executive summary:

Five healthy male and five healthy female New Zealand Albino rabbits were dosed dermally with the test substance at 1000, 1600, 2000 and 2500 mg/kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded on days 1, 7 and 14. Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours post dose and once daily for 14 days. All animals were observed twice a day for mortality. Body weights were recorded pretest, weekly and at death or termination in the survivors. All animals were examined for gross pathology. The deaths occurred by day 4 and were preceded by physical signs of diarrhea, lethargy, ptosis, dyspnea, negative righting reflex, ataxia, few feces, yellow nasal discharge, red discharge and soiling of the anogenital area, convulsions and mucoid diarrhea. Necropsy of the dead animals revealed abnormalities of the lungs, liver, spleen, pleural cavity, eyes, treated skin, kidneys, heart and gastrointestinal tract, as well as soiling of the anogenital area, wetness of the nose/mouth area, wetness of the anogenital area and red staining of the anogenital area. Physical signs noted in survivors included lethargy, ptosis, yellow nasal discharge, diarrhea, ataxia, dyspnea, few feces, emaciation, soiling of the anogenital area, red discharge, ocular discharge, red staining of the anogenital and mucoid diarrhea. Body weight changes of survivors were generally normal, although instances of weight loss were noted in survivors of all groups. Necropsy results of survivors revealed abnormalities of the treated skin, gastrointestinal tract, lungs, liver and kidneys. The LD 50's and 95 Confidence Limits are: males · 1700 (1300 · 2200) mg/kg; females · 1800 (1300 · 2500) mg/kg; and males & females combined · 1700 (1300 - 2200) mg/kg.