Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 November 2008 and 10 December 2008.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols with no deviations from standard test guidelines and/or minor methodological deficiences which do not affect the quality of the relevant results

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
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:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age.
- Weight at study initiation: Males:254-337g; Females: 213 - 234 g
- Fasting period before study: No
- Housing: The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed
individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Free access to food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was
allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: Minimum of 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and
twelve hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: On the day before treatment the back and flanks of each animal were clipped free of hair.
- % coverage: approximately 10% of the total body surface area.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive
bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 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.
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw.
The appropriate amount of test material, moistened with distilled water, was applied as evenly as possible to an area of shorn skin
VEHICLE
The appropriate amount of test material, moistened with distilled water, was applied as evenly as possible to an area of shorn skin
Duration of exposure:
24h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen
days.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for
Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
Statistics:
n/a

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Bodyweight at 14 days:
Males - 283 to 372 g
females - 217 - 241 g
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Red coloured staining, which prevented evaluation of erythema, was noted at the treatment sites of all animals during the study. Small superficial scattered scabs were noted at the treatment site of one female nine to fourteen days after dosing

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 substance in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

In an Acute dermal toxicity (limit test) in the rat study (Harlan project number: 0959/0237) the test material was determined to have an LD50of greater than 2000 mg/kg bodyweight. The study was performed to assess the acutedermaltoxicity of the substance in the Wistar strain rat.

The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987).

- Method B3 Acute Toxicity (Dermal) of Commission Directive 92/69/EEC. There were no deaths. No signs of systemic toxicity were noted.

Red coloured staining, which prevented evaluation of erythema, was noted at the treatment sites of all animals during the study. Small superficial scattered scabs were noted at the treatment site of one female nine to fourteen days after dosing. No abnormalities were noted at necropsy. There were no signs of systemic toxicity and there were no uscheduled deaths during the study.