Use of Information on Repeated Dose Toxicity in Hazard Assessment

5 Use of Information on Repeated Dose Toxicity in Hazard Assessment 

If local effects are clearly identified after repeated dosing, a NOAEL and/or LOAEL should be derived for these effects in addition to NOAEL and/or LOAEL derived for systemic effects. Supportive evidence for the occurrence or absence of local effects after repeated dermal and inhalation exposure may be available from the total toxicity profile of the substance. It should be noted that lack of evidence for local effects in any type of study (i.e., skin or eye irritation, sensitization, repeated dose toxicity study by routes other than the route of interest) does not exclude the possible occurrence of local effects upon repeated respiratory or dermal exposure (EC 2003). 

Substances, which are skin or eye irritating or corrosive after single exposure (Section 4.5) should be suspected of inducing local effects upon repeated respiratory exposure to low concentrations. In contrast, local effects reported from skin sensitization studies as well as dermal repeated dose toxicity studies are not predictive of local effects on the respiratory tract. In addition, observations from irritation and/or sensitization studies as well as repeated dose inhalation toxicity studies are not predictive of local effects on the skin upon repeated dermal exposure (EC 2003). 

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