Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

The toxicological database for inhaled NDI 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 two- or multi-generation studies are available for NDI, acute and subchronic inhalation studies show toxicity confined to the respiratory tract. However, neither gross pathological nor histopathological changes of the reproductive organs were reported at exposure concentrations revealing respiratory tract toxicity. Therefore, based on the studies performed with NDI, there is no indication of a reproductive toxicity potential.

In general, the toxicological effects observed resulting from inhalation exposure of NDI, reveal a pattern characteristic for local irritation and its sequelae with lack of systemic toxicity. This mode of action is in line with other diisocyanates and wholly consistent with the chemical reactivity of the isocyanate functional group. From that perspective any NOAEL established on pulmonary endpoints is highly protective for extrapulmonary and gonadal toxicity.

While there are no reproductive toxicity studies with NDI there are investigations with other diisocyanates, TDI and HDI. Both of these diisocyanates, like NDI, produce toxicological effects only at the portal site of entry. Any other manifestations of toxicity are secondary to this. Neither is a reproductive toxicant. Therefore, it is proposed that, based on the similar major mode of action as port of entry toxicant, the lack of reproductive toxicity seen with TDI and HDI applies equally to NDI (read across). Therefore, based on read across there is no indication of a reproductive toxicity potential.

Overall it can be concluded that the available data from NDI and other diisocyanates are adequate for the purpose of classification and labeling.

Protection against respiratory tract toxicity will protect against any secondary effects. In addition, the need to adopt risk management measures to protect against the sensitising potential of these chemicals provides enhanced safeguards. Therefore, it can be concluded that the available data on NDI are adequate for the purpose of risk assessment.

In line with Annex XI, Section 1.1.2 the available information on the reproductive toxicity potential of NDI is adequate for the purpose of classification and labeling and/or risk assessment. Taking all these points into account (weight of evidence), it is concluded that reproductive toxicity is not an endpoint of concern for NDI and therefore according to Annex XI, Section 1.2 further testing for that property shall be omitted.


Short description of key information:
Neither two- nor multi-generation studies are available for NDI. Data waiver is claimed.

Effects on developmental toxicity

Description of key information
Neither developmental toxicity nor teratogenicity studies are available for NDI. Data waiver is claimed.
Additional information

The toxicological database for inhaled NDI 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 developmental toxicity studies are available for NDI, acute and subchronic inhalation studies show toxicity confined to the respiratory tract.

In general, the toxicological effects observed resulting from inhalation exposure of NDI, reveal a pattern characteristic for local irritation and its sequelae with lack of systemic toxicity. This mode of action is in line with other diisocyanates and wholly consistent with the chemical reactivity of the isocyanate functional group. From that perspective any NOAEL established on pulmonary endpoints is highly protective for extrapulmonary toxicity.

While there are no developmental toxicity studies with NDI there are investigations with the diisocyanates MDI, TDI and HDI. All these diisocyanates, like NDI, produce toxicological effects only at the portal site of entry. Any other manifestations of toxicity are secondary to this. Developmental toxicity studies with MDI, TDI and HDI have shown no evidence of any diisocyanate being a developmental toxicant. Mild effects on the foetuses seen with high level exposures to these diisocyanates are considered secondary to the toxicity to the respiratory system of the exposed dams. Therefore, it is proposed that, based on the similar major mode of action as port of entry toxicant, the lack of developmental toxicity seen with MDI, TDI and HDI applies equally to NDI (read across). Therefore, based on read across there is no indication of a developmental toxicity potential.

Overall it can be concluded that the available data from NDI and other diisocyanates are adequate for the purpose of classification and labeling.

Protection against respiratory tract toxicity will protect against any secondary effects. In addition, the need to adopt risk management measures to protect against the sensitising potential of these chemicals provides enhanced safeguards. Therefore, it can be concluded that the available data on NDI are adequate for the purpose of risk assessment.

In line with Annex XI, Section 1.1.2 the available information on the developmental toxicity potential of NDI is adequate for the purpose of classification and labeling and/or risk assessment. Taking all these points into account (weight of evidence), it is concluded that developmental toxicity is not an endpoint of concern for NDI and therefore according to Annex XI, Section 1.2 further testing for that property shall be omitted.

Justification for classification or non-classification

Toxicity to reproduction (fertility, developmental toxicity/teratogenicity)

Not classified under Annex I of Directive 67/548/EEC. According to Annex I of Regulation (EC) No 1272/2008 no classification is required for toxicity to reproduction.