Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983-09-22 to 1983-10-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Principles of method if other than guideline:
14-day repeat dermal test
GLP compliance:
yes
Test type:
other: 14-day repeat dermal test

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain:Sprague-Dawley
- Sex. male
- Age: adult
- Weight at study initiation: Males: 400 - 450 g
- Housing: single
- Diet: ad libitum, Rat and Mouse Expanded Diet No. 1, Special Diet, Services Limited, Witham, Essex, U.K.)K,
- Water (e.g. ad libitum): tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3 °C
- Humidity (%): 50 - 80 %
- Photoperiod (hrs dark / hrs light): 12 hours daily

Administration / exposure

Type of coverage:
semiocclusive
Details on dermal exposure:
- The hair was shaved from the back and flanks of all animals approximately 24 hr before first treatment.
- Each day for 14 days each animal was subject to the following procedure.
Animal weighed and weight recorded.
Animals condition and behaviour observed.
The appropriate volume of test-article was dispensed onto a predetermined quarter of the shaved area.
Care was taken to avoid application of test-article to skin which had visible damage from a previous treatment.
Control animals received no treatment.
The treated area was covered with a gauze patch, held in place by non-irritant adhesive tape
After 6 hr the rat was released from the restraining cage and the dressings removed.
The treated area was washed gently with tap-water to remove any remaining test-article.
Duration of exposure:
6 hours
Doses:
4
No. of animals per sex per dose:
8
Control animals:
yes
Details on study design:
The rat was observed and any abnormalities of behaviour or condition not noted at the morning examination were recorded.

Assessment of degree of irritation
The degree of irritation present in the treated skin was scored numerically

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 1 mL/kg bw
Based on:
test mat.
Remarks on result:
other: No animals died but skin effects were so severe that treatment was stopped after 4 days. More prolonged treatment with test item was not possible.
Mortality:
No deaths occurred during the study.
Clinical signs:
There were no visible signs of systemic toxicity during the study
At a dose of 1.0 ml/kg/day the test-article produced a very severe skin response consisting of extensive eschar formation and ulceration. This response was so severe that treatment was discontinued after 4 days, both to avoid unnecessary suffering and because there was insufficient unaltered skin to which treatment could be applied.
Body weight:
The rats given the 1.0 ml/kg/day dose of test item lost an average of 60 g during the four-day treatment compared with a slight (4 g) gain by the controls. The treated rats gained weight when dosing was stopped and although the gain over the 14-day period of the study was less than the control the gain over the last ten days was higher than control.
Gross pathology:
At post-mortem examination no difference was seen between treated and control animals in the appearance of any of the tissues apart from the treated areas of skin.

Any other information on results incl. tables

No deaths occurred during the study, however at a dose of 1.0 ml/kg/day the test-article produced a very severe skin response consisting of extensive eschar formation and ulceration. This response was so severe that treatment was discontinued after 4 days, both to avoid unnecessary suffering and because there was insufficient unaltered skin to which treatment could be applied.

There were no visible signs of systemic toxicity during the study and, within the limits of a gross examination, no organ damage was seen at autopsy. The rats given the 1.0 ml/kg/day dose of test item lost an average of 60 g during the four-day treatment

compared with a slight (4 g) gain by the controls. The treated rats gained weight when dosing was stopped and although the gain over the 14-day period of the study was less than the control the gain over the last ten days was higher than control.

These changes of weight gain possibly reflect a toxic change but might be due to a reduced food intake resulting from the discomfort caused by the severe irritation. Without more detailed data it is not possible to separate these two possibilities.

Applicant's summary and conclusion

Conclusions:
The dermal LD50 is > 1 ml/kg in rats.
Executive summary:

The test material is corrosive and with the exception of local effects at the site of administration the test material doesn't appear to cause systemic effects when applied dermally to the skin of rats.