EVALUATION OF ACUTE DERMAL TOXICITY

OECD 402

PRINCIPLE OF THE TEST

The test substance is applied to the skin in one dose (limit test) or graduated doses to several groups of experimental animals (full test), one dose being used per group. Subsequently, observations of effects and deaths are made. Animals which die during the test are necropsied, and at the conclusion of the test the surviving animals are sacrificed and necropsied. Animals showing severe and enduring signs of distress and pain may need to be humanely killed. Dosing test substances in a way known to cause marked pain and distress due to corrosive or irritating properties need not be carried out.

Performance of the test

The test substance should be applied uniformly over an area which is approximately 10 per cent of the total body surface area. With highly toxic substances the surface area covered may be less, but as much of the area should be covered with as thin and uniform a film as possible.

Test substances should be held in contact with the skin with a porous gauze dressing and non-irritating tape throughout a 24-hour exposure period. The test site should be further covered in a suitable manner to retain the gauze dressing and test substance and ensure that the animals cannot ingest the test substance. Restrainers may be used to prevent the ingestion of the test substance, but complete immobilisation is not a recommended method. At the end of the exposure period, residual test substance should be removed, where practicable using water or an appropriate solvent.

Observation RESULTS

Observations should be recorded systematically as they are made. Individual records should be maintained for each animal. Following application of the test substance, the animals should be observed frequently during the first day and then a careful clinical examination should be made at least once each day. Additional observations should be made daily with appropriate actions taken to minimise loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals. Cageside observations should include changes in fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention should be directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The time of death must be recorded as precisely as possible.

Individual weights of animals should be determined shortly before the test substance is applied, weekly thereafter, and at death; changes in weight should be calculated and recorded when survival exceeds one day. At the end of the test surviving animals are weighed and then sacrificed.

CONCLUSION

According to directives 93/21/E.E.C, 2001/59/EC and 99/45/EC concerning the labelling and classification of dangerous substances and preparations, the item under investigation could be classified as follows:

 

LD50

Classification

Symbol

Indication of danger

LD50 £ 50 mg/kg

R27 very toxic in contact with the skin

T+

Very toxic

50mg/kg < LD50£ 400mg/kg

R24 : toxic in contact with the skin

T

Toxic

400mg/kg < LD50 £ 2000 mg/kg

R21 : harmful in contact with the skin

Xn

Harmful

LD50 > 2000 mg/kg

 

According to the Regulation (EC) No. 1272/2008, the item under investigation could be classified as follows:

LD50

Classification

Signal word

LD50 £ 50 mg/kg

Category 1

“H310 Fatal in contact with the skin”

Danger

50 mg/kg < LD50 £ 200 mg/kg

Category 2

“H310 Fatal in contact with the skin”

Danger

200 mg/kg < LD50 £ 1000 mg/kg

Category 3

“H311 Toxic in contact with the skin”

Danger

1000 mg/kg < LD50 £ 2000 mg/kg

Category 4

“H312 Harmful in contact with the skin”

Warning

LD50 > 2000 mg/kg

Price

Turnaround

3 weeks

€ : < 1500 € €€ : between 1500 and 4000 € €€€ : between 4000 and 20000 € €€€€ : > 20000 €
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