Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 January 1994 to 10 February 1994
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

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))
Version / remarks:
Commission Directive 92/69/EEC
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
SPECIFICATION
- Five male and five female Sprague-Dawley rats were supplied by Harlan UK Ltd, Blackthorn, Bicester, Oxon, UK.
- At the start of the study animals were 213-234 g (males) or 210-232 g (females) and were 10-14 weeks old.
- After an acclimatisation period of at least 5 days, animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and recording of the number on a cage card.

HUSBANDRY
- Animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes.
- 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 (Rat and Mouse Expanded Diet No 1, Special Diets Services Limited, Witham, Essex, UK) was allowed during the study.
- The animal room was maintained at a temperature of 19 to 22 °C and humidity of 30 to 51 %.
- Rate of air exchange was approximately 15 changes per hour.
- Lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
PROCEDURE
- On the day before treatment, the back and flanks of each animal were clipped free of hair using veterinary clippers to expose a skin area of approximately 5 cm x 4 cm.
- Five male and five female rats were treated with the test item at a dose level of 2000 mg/kg.
- The appropriate amount of the test material (as received) was pre-weighed into a glass vial.
- Test material was applied uniformly to an area of shorn skin (approximating to 10 % of the total body surface area) which had been previously moistened with distilled water.
- A piece of surgical gauze measuring 7 cm x 4 cm was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end.
- The animals were caged individually for the 24-hour exposure period.
- Shortly after dosing the dressings were examined to ensure 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 item.
- Animals were returned to group housing for the remainder of the test period.
- Test sites were examined for evidence of primary irritation and scored according to the Draize evaluation scheme (attached).
- Animals were observed for deaths or overt signs of toxicity at 0.5, 1, 2 and 4 hours after dosing then once daily for the subsequent 14 days.
- The animals were also observed for any dermal reactions after removal of the dressings and subsequently once daily for the remainder of the study.
- Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five male and five female
Control animals:
no
Statistics:
EVALUATION OF DATA
- Data evaluations included any relationship between exposure of animals to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
- Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- No animal deaths took place during the study.
- Mortality data is given in Table 1 (attached).
Clinical signs:
- No signs of systemic toxicity were noted during the study.
- Individual clinical observations are given in Table 1 (attached).
Body weight:
- All animals showed expected gain in bodyweight during the study except for one female which showed bodyweight loss during the first week and expected bodyweight gain during the second week.
- Individual bodyweights are given in Table 3 (attached) together with weekly bodyweight gains.
Gross pathology:
- No abnormalities were noted at necropsy.
- Individual necropsy findings are given in Table 4 (attached).
Other findings:
DERMAL REACTIONS
- Very slight to well-defined erythema was noted at the treatment sites of all animals.
- Very slight oedema was noted at the treatment sites of two males.
- Desquamation and/or slight haemorrhage of dermal capillaries was noted at the treatment sites of three animals.
- Loss of skin elasticity was confined to one male.
- Treatment sites appeared normal three to seven days after dosing.
- Individual dermal reactions are given in Table 2 (attached).

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley rat was determined to be > 2000 mg/kg bw.
Executive summary:

A study was performed in accordance with OECD 402 and EU Method B.3 to assess the acute dermal toxicity of the test material in Sprague-Dawley rats. A group of ten animals (five males and five females) was given a single 24 -hour semi-occluded dermal application of test material to intact skin at a dose level of 2000 mg/kg bw. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination. No animal deaths took place during the study. No signs of systemic toxicity were noted and signs of skin irritation were very slight to well-defined erythema, very slight oedema, slight haemorrhage of dermal capillaries, desquamation and loss of skin elasticity. The treatment sites appeared normal 3 to 7 days after dosing. All animals showed expected gain in bodyweight during the study except for one female which showed bodyweight loss during the first week and expected bodyweight gain during the second week. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley rat was determined to be > 2000 mg/kg bw.