Registration Dossier

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: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Description: clear colourless liquid
Storage conditions: room temperature in the dark
Purity: 99.4 %
Water content: 0.02 %

Test animals

Species:
rabbit
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of et least five dayx the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The animal weighted at least 200g, and the bodyweight variation did not exceed ± 20% of the mean bodyweight for female animals. For male animals, the bodyweight variation of one male did exceed ↑1 20% of the mean bodyweight. This deviation from the Standard test Method was considered not to affect the purpose or intergrity of the study.

The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
The animals were housed individually during the 24-hour exposure period and in groups of up to four, by sex, for the remainder of the study. Free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to acheive limits of 19 to 25°C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchenge was at least fifteen changes per hour and the ligjting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain anay contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair.
The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10 % of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.
Duration of exposure:
The animals were caged individually for the 24-hour exposure period and for the remainder of the test.
Shortly after dosing the dressings were examined to ensure that they were securely in place.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
The animals were observed for overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity/mortality inspections were also performed twice daily, eraly and late, during normal working days and once daily at weekends.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored.
Individual bodyweights were recorder on day 0 and on days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:
No mortalities were noted after the 24-hour contact period in one male and one female
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no death
Clinical signs:
There were no signs of systemic toxicity.
There were no signs of dermal irritation.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found greater than 2000 mg/kg bodyweight.
Executive summary:

In a GLP-compliant acute toxicity study conducted in accordance with standardised guideline OECD 402, the LD50 of the test material was calculated by exposing 5 males and 5 females Wistar rats to a dose of 2000 mg/kg of body weight by contact. Under the conditions of the test no systemic signs of toxicity were reported over a period of 14 days and the LD50 was determined to be > 2000 mg/kg.