User Guide to Thresholds and Classification - Environmental ...

270User Guide for Thresholds and Classificationscrosses into6.9BHarmful (Xn)A substance is determined to be hazardous and classified as Harmful (Xn) and assigned one ormore of the following risk phrases in accordance with the criteria given below.R48 Danger of serious damage to health by prolonged exposureSerious damage (clear functional disturbance or morphological changes that have toxicologicalsignificance) is likely to be caused by repeated or prolonged exposure by an appropriate route.Substances are classified at least as Harmful (Xn) when these effects are observed at thefollowing dose ranges:inhalation, rat 0.25 mg/L, 6 hours/day;oral, rat 50 mg/kg bw/day; anddermal, rat or rabbit 100 mg/kg bw/day.These guide values can apply directly when severe lesions have been observed in a subchronic(90 days) toxicity test. As a guideline, when interpreting the results of a sub-acute (28 days)toxicity test these figures should be increased at least threefold. If a chronic (two years) toxicitytest is available, it should be evaluated on a case-by-case basis. If results of studies of more thanone duration are available, then those from the study of the longest duration should normally beused.6.9ANotes: bw = bodyweight; LC 50 = median lethal concentration; LD 50 = median lethal dose; mg/kg = milligrams perkilogram; mg/L = milligrams per litre.Source: EC (1967).ReferencesEC 1967. General classification and labelling requirements for dangerous substances and preparations.Council Directive 67/548/EEC of 27 June 1967 on the Approximation of Laws, Regulations andAdministrative Provisions Relating to the Classification, Packaging and Labelling of Dangerous Substances.European Commission, Annex VI. http://ec.europa.eu/environment/dansub/consolidated_en.htm.January 2012 EPA0109