416-730-1

Acute Toxicity: dermal

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 and guideline conform

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of healthy male and female CD rats of Sprague-Dawley origin (Hsd/01a:Sprague-
Dawley(CD)) were obtained from Harlan Olac Ltd., Bicester, Oxon, England.
They were in the weight range of 215 to 256 g and approximately seven to ten weeks of age prior
to dosing (Day 1). All the rats were acclimatised to the experimental environment for a period of six
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 metal cages with wire mesh floors in Building R14 Room 6.
A standard laboratory rodent diet (Biosure LAD 1) and drinking water were provided ad libitum.
Each batch of diet used for the smdy 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 Research Centre Ltd. (as quarterly
summaries).
The mean daily minimum and maximum temperamres of the animal room were 21 °C and 24°C
respecdvely and the mean daily relative humidity value was 52% R.H. Air exchange was maintained
at 10 to 15 air changes per hour and lighting was controlled by means of a time switch to provide
12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.
Each animal was identified by cage number and ear punching. Each cage was identified by a
coloured label displaying the dose level, smdy schedule number, animal mark and the initials of the
Smdy Director and Home Office licensee

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

- treated area was covered with gauze which was held in place with a non-irritative dressing encircled firmly around the trunk

Duration of exposure:

24 h

Doses:

2 g/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- duration of observation period following administration: 14d
- frequency of observation : twice a day
- frequency of weighting: at day 1, 8, 15

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no mortality and no signs of specific toxicity observed

Mortality:

none

Clinical signs:

There were no signs of systemic reaction to treatment

Body weight:

A slightly low bodyweight gain was recorded for one male and one female on Day 8 and in three males on Day 15. All other rats achieved the anticipated bodyweight gains throughout the study

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Other findings:

Sites of application of the test substance showed no irritation or other dermal changes. However, a residual yellow staining was evident in a number of animals during the study clearing in all instances by Day 15.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute lethal dermal dose to rats of test item was found to be greater than 2.0 g/kg bodyweight.

Executive summary:

A group of ten rats (five males and five females) was given a single dermal application of the test substance, at a maximum practical concentration of 71.43% w/v in distilled water, and at a dose level 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 the test item showed no irritation or other dermal changes. However, a residual yellow staining was evident in a number of animals during the clearing in all instances by Day 15. A slightly low bodyweight gain was recorded for one male and one female on Day 8 and in three males on Day 15. All other rats achieved the anticipated bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal dermal dose to rats was found to be greater than 2.0 g/kg bodyweight.