Commission Directive 2004/73/ECShow full title

ANNEX 2 U.K.

CRITERIA FOR CLASSIFICATION OF TEST SUBSTANCES WITH EXPECTED LD₅₀ VALUES EXCEEDING 2000 MG/KG WITHOUT THE NEED FOR TESTING U.K.

Criteria for hazard Category 5 are intended to enable the identification of test substances which are of relatively low acute toxicity hazard but which, under certain circumstances may present a danger to vulnerable populations. These substances are anticipated to have an oral or dermal LD50 in the range of 2000-5000 mg/kg or equivalent doses for other routes. The test substance should be classified in the hazard category defined by: 2000mg/kg < LD₅₀ < 5000mg/kg (Category 5 in the GHS) in the following cases:

a)

If directed to this category by any of the testing schemes of Annex 1a-1d, based on mortality incidences;

b)

if reliable evidence is already available that indicates the LD₅₀ to be in the range of Category 5 values; or other animal studies or toxic effects in humans indicate a concern for human health of an acute nature.

c)

through extrapolation, estimation or measurement of data if assignment to a more hazardous class is not warranted, and

• reliable information is available indicating significant toxic effects in humans, or

• any mortality is observed when tested up to Category 4 values by the oral route, or

• where expert judgement confirms significant clinical signs of toxicity, when tested up to Category 4 values, except for diarrhoea, piloerection or an ungroomed appearance, or

• where expert judgement confirms reliable information indicating the potential for significant acute effects from the other animal studies.

TESTING AT DOSES ABOVE 2000 MG/KG U.K.

Recognising the need to protect animal welfare, testing of animals in Category 5 (5000 mg/kg) ranges is discouraged and should only be considered when there is a strong likelihood that results of such a test have a direct relevance for protecting human or animal health (10). No further testing should be conducted at higher dose levels.

When testing is required a dose of 5000mg/kg, only one step (i.e. three animals) is required. If the first animal dosed dies, then dosing proceeds at 2000mg/kg in accordance with the flow charts in Annex 1. If the first animal survives, two further animals are dosed. If only one of the three animals dies, the LD50 value is expected to exceed 5000mg/kg. If both animals die, then dosing proceeds at 2000mg/kg.