Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

There is no evidence from the experimental studies to indicate that MDI category members are absorbed systemically. No information on distribution, metabolism or excretion can be derived from the experimental data.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Experimental data for the mammalian toxicity Annex VII and VIII endpoints have been generated on substances within the MDI category.

 

The following conclusions can be drawn on the basis of a review of available key experimental data from physico-chemical and toxicological studies on the isolated substances performed according to international technical guidelines and in compliance with GLP:

 - MDI category substances do not appear to be absorbed via the gastrointestinal tract. This is supported by the lack of systemic toxicity at single doses of up to 2000 mg/kg bw, as suspension via oral gavage in the acute oral toxicity studies with Wistar rats and the repeat oral toxicity studies with Wistar rats at concentrations up to 1000 mg/kg/bw. Additionally, this conclusion is supported by the data from the read-across study conducted on Diurea 8, following repeated daily oral gavage dosing at lower concentrations to male and female rats for at least 42 days. Alternatively the lack of toxicity via the oral route may also be indicative of high-threshold toxicity for the substance over the relatively short-term exposures examined.

 

- MDI substances do not appear to be absorbed via the skin. This is supported by the lack of any systemic effects following occluded, or semi-occluded, application of 0.5 g to rabbit skin in vivo studies. Similarly, there was no dose dependent increases in stimulation index following topical application of MDI substance in a local lymph node assay. Additionally, in modified Buehler tests and guinea-pig maximisation tests no classifiable response was observed. There is also a lack of systematic toxicity in acute dermal toxicity studies conducted on four MDI category members. Although lack of dermal absorption is the likely scenario for the absence of systemic effects via this route of exposure, the alternative explanation of high threshold toxicity over the short-term exposure examined cannot be ruled out.

No available data from these studies allows conclusions to be drawn regarding distribution, metabolism or excretion of the polyurea MDI substances in the marketed grease base.