Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 12 to February 26, 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline test with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

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:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Identity:BM1-Resin
Chemical identity:Epoxide resin based on Bisphenol A and epichlorohydrin blocked with paraphenylphenol
Intended use:Resin in toner for use in copier/printers
Appearance: White (slightly yellow) powder
Storage conditions:Room temperature
Batch number: 20001097/B160295/111
Expiry:Not advised
Purity:>98%
Date received:15 January 1996

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
ANIMAL MANAGEMENT
Equal numbers of healthy male and female CD rats of Sprague-Dawley origin (Hsd:Sprague- Dawley(CD)) were obtained from Harlan U.K. Ltd., Bicester, Oxon, England.
They were in the weight range of 228 to 300 g and approximately seven to ten weeks of age prior to dosing (Day 1). Rats were acclimatised to the experimental environment for a minimum period of 25 days prior to the Start of the study.
The rats were allocated without conscious bias to cages within the treatment group. They were housed individually in meta1 cages with wire mesh floors in Building R14 Room 6.
A standard laboratory rodent diet (SDS LAD 1) and drinking water were provided ad libitum. Each batch of diet used for the study was analysed for certain nutrients, possible contaminants and micro-organisms.
Results of routine physical and chemical examination of drinking water at source as conducted, usually weekly by the supplier are made available to Huntingdon Life Sciences Ltd. as quarterly summaries.
Animal room temperature was Set to achieve a temperature of 22 ± 3°C. Relative humidity was not controlled but was anticipated to be in the range 30 - 70% RH. Permanent daily recordings of these Parameters were made and these are archived with other Department raw data. Any slight deviatiori
in temperature and humidity that may have occurred was not considered to have affected the integrity or validity of the study. Air exchange was maintained at 10 to 15 air changes per hour and lighting controlled by means of a time switch to provide 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.
Each animal was identified by cage number and ear punching. Each cage was identified by a coloured labe1 displaying the dose level, study schedule number, animal mark and the initials of the Study Director and Home Office licensee.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight.
One day prior to treatment hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to approximately 10% of the total body surface. The test substance was applied by spreading it evenly over the prepared skin. The treated area (approximately 50 mm X 50 mm) was then promptly covered with gauze which was held in place with a non- irritative dressing encircled firmly around the trunk.
At the end of the 24 hours exposure period, the dressings were carefully removed and the treated area of skin was washed with warm (30 to 40°C) water and blotted dry with absorbent Paper.
The day of dosing was designated Day 1 .
Duration of exposure:
24 hours
Doses:
2.0 g/kg bodyweight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
TEST SUBSTANCE PREPARATION
BM1-Resin was formulated at a maximum practical concentration of 70% w/v in 1 % w/v aqueous methylcellulose and administered at a volume of 2.9 ml/kg bodyweight.
The test substance was prepared on the day of dosing. The absorption of the test substance was not determined. The homogeneity, stability and purity of the test substance were the responsibility of the Sponsor.
Mortality
Cages of rats were checked at least twice daily for any mortalities.
Clinicai signs
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of four hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturdays and Sundays. The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing.
Dermal responses
Local dermal irritation at the treatment site was assessed daily using the following numerical System:
Erythema and eschar formation:
No erythema 0
SI ight erythema 1
Well-defined erythema 2
Moderate erythema 3
Severe erythema @eet redness) to slight
eschar formation (injuries in depth) 4
Oedema formation:
No oedema 0
Slight oedema 1
Well-defined oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre
and extending beyond the area of exposure) 4
Bodyweight
Individual bodyweights were recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
Macroscopic examination
All animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all examined tissues was recorded.
Statistics:
no data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No treat-related effects were observed during the test.
Mortality:
No death
Clinical signs:
There were no signs of systemic reaction to treatment.
DERMAL RESPONSES
Sites of application of BM1-Resin showed no irritation or other dermal changes (scores of zero for erythema and oedema were recorded for all animals).
Body weight:
In comparison with historical data from the Department of Industrial Toxicology, a slightly low bodyweight gain was recorded for two males and two females on Day 8, with a similar trend noted for one male and two females on Day 15. All other rats achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for animals killed on Day 15.
Other findings:
no data

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of acute dermal toxicity to rats was found to be greater than 2000 mg/kg body weight based on this results given in this report.
Executive summary:

This study was performed to assess the acute dermal toxicity of test article to the rat. The method followed was that described in OECD Guideline for Testing of Chemicals No. 402.

A group of ten rats (five males and five females) was given a single dermal application of the test substance, formulated at a maximum practical concentration of 70% w/v in 1 % w/v aqueous methylcellulose and administered at a dosage of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths and no signs of systemic reaction to treatment. Sites of application of test article showed no irritation or other dermal changes. In comparison with historical data from the Department of Industrial Toxicology, a slightly low bodyweight gain was recorded for two males and two females on Day 8, with a similar trend noted for one male and two females on Day 15. All other rats achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15.

Therefore, the acute lethal dermal dose to rats of test substance was found to be greater than 2.0 g/kg bodyweight.