Registration Dossier

Administrative data

Description of key information

- Skin sensitisation:

The sensitisation potential of 3,4-dichlorphenyl isocyanate was evaluated in the guinea-pig by intradermal route and cutaneous application, according to the maximisation method of Magnusson and Kligman (OECD 406). A positive result was found under the experimental conditions.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

- Skin sensitisation:

The sensitisation potential of 3,4-dichlorphenyl isocyanate was evaluated in the guinea-pig by intradermal route and cutaneous application, according to the maximisation method of Magnusson and Kligman (OECD 406). A positive result for all animals (10/10) was found under the experimental conditions. Therefore, a classification as category 1A / H317 is warranted.

- Respiratory sensitisation:

No study available; based on Expert Judgement in a Weight of Evidence approach (ASS 1800110 -1, 04/2018), a classification as category 1 / H334 is assigned.

"The unique feature common to all isocyanates is that they contain N=C=O (isocyanate) functional groups attached to an aromatic or aliphatic parent compound. Isocyanates can cause skin sensitization, asthma, skin or mucous membrane irritation, and, rarely hypersensitivity pneumonitis. However, the most common adverse health outcome associated with isocyanate exposure is asthma due to sensitization.

 

Evidence exists that respiratory sensitization is triggered by dermal induction. In addition, vice versa, topical contact hypersensitivity was observed after previous induction by inhalation. The Technical Guidance Document (TGD) on information requirements for REACH (R.7a; page 256ff) proposes that, in the absence of specific health effects data, only diisocyanates that also meet the criteria for classification for skin sensitization are presumed to be respiratory sensitizers. It is assumed that this recommendation also applies to monoisocyanates such as 3,4-dichlorophenyl isocyanate. 3,4-Dichlorophenyl isocyanate is a strong skin sensitizer in the Magnusson & Kligman Test. It is therefore concluded that 3,4-dichlorophenyl isocyanate is contributing to the development of isocyanate asthma, presumably by inducing systemic sensitization.

 

According to the recent background document to the opinion on the Annex XV dossier proposing restrictions on diisocyanates (https://echa.europa.eu/documents/10162/ddc6108d-a33e-3087-6a6a-8754783c2aa8) RAC considers that for monoisocyanates, based on indirect evidence from humans and animals referenced in that document, the risk of respiratory sensitization in humans cannot be excluded.

 

The German Commission for Investigation of Health Hazards of Chemical Compounds in the Work Area also concluded (see p. 201: https://onlinelibrary.wiley.com/doi/pdf/10.1002/9783527812127.ch4) that sensitizing effects of monoisocyanates on the respiratory tract cannot be ruled out. However, data for the diisocyanates, which are assessed as potent respiratory allergens, would not justify classifying monoisocyanates as substances causing airway sensitization solely in analogy; an evaluation of the individual case is necessary.

 

Information on the individual structural analogues phenyl isocyanate (CAS 103-71-9) and 4-chlorophenyl isocyanate (CAS 104-12-1) support the conclusion that 3,4-dichlorophenyl isocyanate may pose a respiratory health hazard. Workers exposed to phenyl isocyanate showed specific IgE for isocyanate-albumin conjugates. These workers also developed asthmatic symptoms (BG Chemie, Phenylisocyanate Nr. 198, 1997). Furthermore, phenyl isocyanate is classified by German Commission for Investigation of Health Hazards of Chemical Compounds in the Work Area as respiratory sensitizer. 4-Chlorophenyl isocyanate, a close analogue to 3,4-dichlorophenyl isocyanate, is not skin-sensitizing when tested in a split adjuvant test in guinea pigs. However, 4-chlorophenyl isocyanate is classified as respiratory sensitizer according to CLP, Annex VI.

 

Taking all available information into account 3,4-dichlorophenyl isocyanate is classified as respiratory sensitizer in a Weight of Evidence assessment."