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Key value for chemical safety assessment

Effects on fertility

Additional information

Effects on fertility - read-across with other MDI substances:

The toxicological database for inhaled MDI demonstrates consistently that toxicity is associated only with the portal of entry (respiratory tract), any other manifestations of toxicity are secondary to this. While no fertility studies are available for MDI, subchronic and chronic studies all show toxicity confined to the respiratory tract. Fertility studies with TDI and HDI show no effects on reproductive parameters, all effects are confined to the respiratory tract. Hence the databases for MDI, TDI and HDI all show that primary toxicity for diisocyanates is to the respiratory tract, other effects, such as fetotoxicity in developmental studies, are secondary to this. This relationship applies to TDI and HDI when tested in fertility studies in the rat and is considered to apply equally to MDI, i.e., if any effects were to be seen in a fertility study, these would occur only as a secondary effect of the toxicity to the respiratory system of the exposed rats. Protection against respiratory tract toxicity will protect against any secondary effects.

Using the weight of evidence, it is concluded that reproductive toxicity is not an endpoint of concern for MDI and additional toxicity testing is not necessary. 

Short description of key information:
No fertility nor multigeneration studies are available for MDI. Data waiver is claimed

Effects on developmental toxicity

Description of key information
MDI is not a developmental toxicant. 
Additional information

Developmental toxicity / teratogenicity - read-across with other MDI substances:

Based on the available data on polymeric MDI from the study by Gamer et al., 2000, the NOAEL for maternal and fetal toxicity is 4 mg/m3. This key study was conducted according to OECD Guideline 414 (Prenatal Developmental Toxicity Study and GLP with reliability 1). The NOAEL for development/teratogenicity is observed at 12 mg/m3 (Gamer et al., 2000). As the observed fetotoxic effects and adverse effects on the embryonic development are considered as minor signs of developmental toxicity and as these effects occur at the concentration inducing maternal toxicity, they are considered to be secondary to maternal toxicity. As a consequence, polymeric MDI is considered not to be a developmental toxicant.

Justification for classification or non-classification

According to CLP Regulation (EC) No.1272/2008 the non-classification of 4,4'-MDI (CAS No.101-68-8) was considered for the non-classification of MDI MT (CAS No.147993-65-5):

4,4'-MDI was not classified as a reproductive toxicant by DSD or GHS.

Additional information