Registration Dossier

Administrative data

Description of key information

Two reliable studies are available for the analogue 1,3-H6XDI. The data are read across to 1,4-H6XDI.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
In Section 13 of the IUCLID dossier, a report is attached in which the analogue approach is reported according to ECHA Guidance for the implementation of REACH, Guidance on information requirements and chemical safety assessment, Chapter R.6.
Reason / purpose:
read-across source
Positive control results:
Summary of positive control data from 1995 and 1996: 6/10 for benzocaine, 8/10 and 10/10 for HCA, 10/10 (twice) for MBT.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.01% intradermal, 20% epidermal, 2.5% and 5% challenge
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Necrotic effects (necrosis/ necrotic edges/ necrotic patches) in all animals, dryness and sloughinig of the epidermis in one animal, blanching in two animals.
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
n.a.
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Localized dermal reaction (restricted to a small area of the challenge site) was seen in one animal at 24 and 48 hours; dryness and sloughing of the epidermis was observed at 72 hours for another animal.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Not specified
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
Historical data

No signs of ill health or toxicity were noted. Bodyweight increases in test group animals were comparable to control group animals.

Intradermal injections resulted in necrosis at sites receiving Freund's Complete Adjuvant in test and control animals. Slight irritation was seen in test animals at sites receiving Takenate 600, 0.01% v/v in Alembicol D and slight irritation was observed in control animals receiving Alembicol D.

Slight erythema was observed in test animals following topical induction application with Takenate 600, 20% v/v in Alembicol D. Slight erythema was seen in the control guinea pigs.

After challenge, dermal reactions (erythema and oedema) were seen in all of the ten test animals at 24 and 48 hours after challenge, compared to none in the controls. Well-defined erythema was seen in 9/10 animals, in one animal slight erythema was seen.

Oedema formation was slight in one animal, well-defined (edges of area well-defined by definite raising) in 6 animals and moderate (raised approximately 1 mm) in 3 animals.

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
In a skin sensitising test in guinea pigs performed according to OECD guidance and GLP principles, Takenate 600 produced evidence of skin sensitisation (delayed contact hypersensitivity) in all of the ten test animals. This result is read across to 1,4-H6XDI.
Executive summary:

A skin sensitising test in guinea pigs was performed according to OECD guidance and GLP principles. Based on a dose range finder experiment, concentrations for intradermal injection, topical application and challenge application were established at 0.01% v/v, 20% v/v and 2.5%/5% v/v Takenate 600. No signs of ill health or toxicity were noted. Bodyweight increases in test group animals were comparable to control group animals. After challenge, dermal reactions (erythema and oedema) were seen in all of the ten test animals at 24 and 48 hours after challenge, compared to none in the controls. Well-defined (or slight) erythema was seen in 10/10 animals.

Oedema formation was slight in one animal, well-defined (edges of area well-defined by definite raising) in 6 animals and moderate (raised approximately 1 mm) in 3 animals. As the test substance produced evidence of skin sensitisation (delayed contact hypersensitivity) in all of the ten test animals, Takenate 600 was found to be a skin sensitiser (cat. 1A). This result is read across to 1,4-H6XDI.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

For substance analogue 1,3-H6XDI, two studies are available, both performed according to OECD/EC test guidelines and GLP principles. In the first study, a skin sensitising test in guinea pigs, after challenge, dermal reactions (erythema and oedema) were seen in all of the ten test animals at 24 and 48 hours after challenge, compared to none in the controls. In the second, a test for delayed contact hypersensitivity was performed with 1,3-XDI according to Magnusson and Kligman (1970). Challenge resulted in slight to severe dermal reactions (erythema and oedema), in part accompanied by thickening, dryness and sloughing of the skin in 9/10 test animals. Only slight skin effects were seen in one control animal. Based on these data, 1,3-XDI was found to be a skin sensitiser.

These results are read across to 1,4 -H6XDI.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

In accordance with the ECHA Guidance document "Guidance on information requirements and chemical safety assessment, Chapter R.7a: Endpoint specific guidance" of July 2017, diisocyanates need to be considered for classification as a respiratory sensitiser. In the scientific literature diisocyanates are identified as chemicals causing the development of occupational asthma after workplace exposure. There are no data available that show that such a classification is not warranted for 1,4-H6XDI.

Justification for classification or non-classification

Based on the available studies on a substance analogue, 1,4-H6XDI is classified cat.1A for skin sensitising properties according to the CLP Regulation (EC) No. 1272/2008.

As 1,4-H6XDI is a diisocyanate, it is classified according to the CLP Regulation (EC) No. 1272/2008 and ECHA Guidance as

a respiratory sensitiser cat. 1.