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: GLP study, OCDE guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

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)
Remarks:
2003-02-13
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Description : yellow solid block
Batch number : 173 JG1
Date received : 13 October 2004
Storage conditions : room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Five male and five female Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rats were supplied
by Charles River (UK) Ltd, Margate, Kent, UK. On receipt the animals were randomly allocated
to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at
least five days 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 weighed at least 200 g, and were eight to twelve weeks of age. The weight variation
did not exceed ± 20% of the mean weight for each sex.
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. Free access to mains drinking water and
food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK)
was allowed throughout the study. The diet, drinking water and bedding were routinely analysed
and were considered not to contain any contaminants that could reasonably be expected to affect
the purpose or integrity of the study.
The temperature and relative humidity were set to achieve 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 exchange was at least fifteen changes per
hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00
to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to
contain any 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:
The appropriate amount of test material was applied as evenly as possible to an area of shorn skin
(approximately 10% of the total body surface area). A piece of surgical gauze was placed over
the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were
caged individually for the 24-hour exposure period. Shortly after dosing the dressings were
examined to ensure that they were securely in place.
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 returned to group housing for the remainder of the study period.
Duration of exposure:
24 h
Doses:
2000 mg/kg pc
Details on study design:
The animals were observed for deaths or overt signs of toxicity ½, 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

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
There were no signs of dermal irritation.

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) and the maximum sub-lethal dose (LD0) of the test
material in the Sprague-Dawley CD strain rat were found to be greater than 2000 mg/kg
bodyweight.
Executive summary:

Introduction.

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD 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

Method.

A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight.

Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths. Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. There were no signs of dermal irritation.

Bodyweight. All animals showed expected gains in bodyweight over the study period. Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute dermal median lethal dose (LD50) and the maximum sub-lethal dose (LD0) of the test material in the Sprague-Dawley CD strain rat were found to be greater than 2000 mg/kg bodyweight.