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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:
Oct 1996 - Jan 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to the relevant guidance on dermal toxicity, OECD 402.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

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

Test material

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

- Lot/batch No.: HCE 0995
- Specific gravity: 1.02
- purity: 94% (GC)

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Animals were received from Ace Animals, Boyertown, PA. Following the quarantine period of at least one week, five healthy male and five non-pregnant, nulliparous, healthy female were randomly assigned to the treatment groups.The pretest body weight range was 2.0-2.5 kg for males and 2.0-2.6 kg for females. the w eight variation of the animals used did not exceed +/- 20% of the mean body weight.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test artice was used as received. It had been applied to the clipped site by a syringe at 1000 mg/kg bw and 2000 mg/kg bw. The doses were based upon the sample weight as calculated from the specific gravity. The test article was applied on the top of a four layered surgical gauze patch measurig 10x15cm. *Gentle pressure was applied to the gauze to aid in the distribution of the test substance over the prepared site. The torso was wrapped with plastic which was secured with non-irritating tape. The test article remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test article was removed by gentle washing with distilled water.
Duration of exposure:
24 hrs
Doses:
1000 mg/kg bw and 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: The animals were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for 14 days for mortality. The test sites were scored for dermal irritation at 24 hrs postdose and on days 7 and 14 using the numerical Dreize scoring code.
- Frequency of weighing: Body weights were recorded pretest, weekly and at death, or termination of the survivors.
- Necropsy of survivors performed: All animals were examined for gross pathology. Abnormal tissues were preserved in 10% buffered formalin for possible future microscopic examination.
Statistics:
None: the estimate of the LD50 was made based on the survivals during the study.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Dose group 1000 mg/kg bw
females 0/5
males 0/5
Dose group 2000 mg/kg bw
females 1/5
males 3/5
Clinical signs:
Lethargy, soiling on the anogenital area, ataxia, flaccid muscle tone, emaciation, wetness of the nose/mouth and breathing difficulties.
Body weight:
Body weight changes in the low dose group were normal. Body weight changes of the survivors (6) in the high dose group were normal in 2/6 animals, however instances of weight loss were noted in four animals.
Gross pathology:
Animals died during the study revealed abnormalities of the lungs, dosed site, liver and gastrointestinal tract as well as wetness of the nose/mouth and anogenital area, emacination and soiling of the anogenital area. Necropsy of survivors revealed abnormalities of the treated skin, kidneys, liver, lungs, intestines, peritoneal cavity and soiling of the anogenital area.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 is greater than 2000 mg/kg body weight for female rabbits
The LD50 is in the range of 1000 - 2000 mg/kg bw for male rabbits.
Fullfil the criteria for classification as Acute Tox 4; H312
Executive summary:

An OECD 402 study was perfomed with rabbits (5 males, 5 females) at dose levels of 1000 mg/kg bw and 2000 mg/kg bw.

The LD50 was greater than 2000 mg/kg body weight for female rabbits

The LD50 was in the range of 1000 - 2000 mg/kg bw for male rabbits.

The LD50 value for male rabbits fullfils the criteria for classification as Acute Tox 4; H312.