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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Cross-reference
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 10 - April 26, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Age and weight at the beginning of treatment : young adults, 5 to 7 weeks old (the individual weights should not vary by more than 20% of the average weight of the animals for each sex).
- Number and sex : 5 males, 5 non-pregnant females
- Cages : individual housing, in polycarbonate cages of type FI, and of internal dimensions 305 x 180 x 184 mm.
- Environment :
Temperature : 22• ~ 3·c.
Humidity : 30 to 70 % RH.
Lighting : a 12-hour light-dark cycle was maintained (photoperiod
= 7h30- 19h30).
- Rat-mouse pelleted complete maintenance diet, ad libitum (U.A.R. formule
"A. 04 CR" - U .A.R., Villemoisson sur Orge - 91360 Epinay sur Orge -
France).
- Softened and filtered drinking water (15 pm), ad libitum.
Bacteriological and chemical controls every six months.
Pretreatment procedures
- Acclimatization period : minimum of 5 days before the beginning of treatment.
- Clinical examinations on delivery, then before the beginning of treatment, in order to keep only healthy animals for the test.
- Identification : ear perforation before the beginning of treatment.
- Allocation to groups : the animals were allocated to groups, as they came to hand.
- Preparation of the animals : the day before the application of the test article, the back and the flanks of the animals were carefully clipped, to obtain an area of skin which should not be less than 10% of the total body surface area. An electric clipper (Aesculap - Type V 42 947 : Ets. Lepine - 7, rue du Vinatier - 69300 Lyon Bran) equipped with a very fine comb (cutting height : 1/20th mm) was used, in order to get a very precise cut, with no mechanical irritation. Only the animals showing a perfectly healthy skin and with no sign of macroscopic irritation after a rest period of 24 hours, were kept for the test.
Type of coverage:
semiocclusive
Details on dermal exposure:
- Methods of application
The test article was spread over an area equal to approximately 10% of the total body surface. It was spread evenly using a finger covered with a thin natural latex glove and was lightly massages for about 15 seconds, to ensure the penetration of the total or the maximum possible quantity of the test article.
The test article was held in contact with the skin with a bandage composed of a 10 em wide adhesive and perforated tape (Peloplast : M.S.R., Laboratoires Fournier- 9, rue Petitot- 21000 Dijon- France), applied on a crimped gauze bandage (Creplux - Molinier, Laboratoires Molypharm - Rue des Siccards - 42340 Veauche - France) covering the whole clipped area to prevent possible reactions of irritation and surrounding the trunk of the animal without blocking the respiratory and abdominal movements. This bandage entirely covered the treated area, in order to prevent the animals from ingesting the test article . At the end of the application period of the test article, taking into account the lesions observed, no rinsing was carried out.
Duration of exposure:
24 h
Doses:
2003 mg/kg bw
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 003 mg/kg bw
Mortality:
no
Clinical signs:
No behavioural abnormality was noted in the animals at the end of the application of the /test article and for the 14 following days. But, as far as cutaneous tolerance is concerned, a deep eschar formation was observed in all the animals, at the end of application of the test article and until the end of the observation period (Day 15) .
Body weight:
The body weight changes of the treated animals were rather identical to that of non-treated rats housed under the same conditions for the 2 week observation period which followed treatment.
Gross pathology:
The significant macroscopic abnormalities which were noted in all the animals killed at the end of the observation period are characterized by a total necrosis of the tissues to the application area ; adhesion of the skin to the subjacent tissues ; severe congestion and oedema of the sub-cutaneous tissue.

Male No 1101

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Male No 1102

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Male No 1103

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Male No 1104

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Male No 1105

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Female No 1201

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Female No 1202

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Female No 1203

Subcutaneous tissue - application site : marked congestion

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Female No 1204

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Female No 1205

Subcutaneous tissue - application site : marked congestion.

Adherence of the skin to the subjacent tissues.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Oedema of the sub-cutaneous tissue.

Total necrosis of the tissue to the application area.

Interpretation of results:
GHS criteria not met
Conclusions:
The macroscopic examination showed a necrosis of the tissues to the application area. No mortality was noted. From the results obtained under the experimental conditions, only the LD 0 can be expressed as follows: LD 0, by the cutaneous route, in the rat (male + female) ~ 2003 mg/kg.
Executive summary:

The test article was applied as supplied, once only and at the dose level of 2003 mg/kg, by the cutaneous route, in the Sprague-Dawley rat (5 males +5 females).

The mortality and abnormal clinical signs were noted 15 minutes after application, then at 1, 2 and 4 hours, and then daily for the 14 day study period. All the animals were weighed immediately before application of the test article (Day 1), on Day 8 and Day 15. A necropsy was performed for all the animals after the 14 day study period and the

final observation (Day 15).

The macroscopic examination showed a necrosis of the tissues to the application area. No mortality was noted. From the results obtained under the experimental conditions, only the LD 0 can be expressed as follows: LD 0, by the cutaneous route, in the rat (male + female) ~ 2003 mg/kg.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion