p-isopropylphenyl isocyanate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: cited in BG 249 (Hoechst study)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

1988 OECD 406 was the standard test for skin sensitisation, LLNA test guidance OECD 429 was not available at that time.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Route:

intradermal

Vehicle:

paraffin oil

Concentration / amount:

1st: induction: 0.1 ml of a 0.5% p-isopropylphenyl isocyanate solution + freund complete adjuvans
2nd: induction: 0.5 ml of a 10% sodiumlaurylsulfat solution (day 8)
3rd induction: 0.5 ml of a 10% p-isopropylphenyl isocyanate solution (day 9)
challenge: 0.5 ml of 10% p-isopropylphenyl isocyanate solution (day 15)

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Concentration / amount:

1st: induction: 0.1 ml of a 0.5% p-isopropylphenyl isocyanate solution + freund complete adjuvans
2nd: induction: 0.5 ml of a 10% sodiumlaurylsulfat solution (day 8)
3rd induction: 0.5 ml of a 10% p-isopropylphenyl isocyanate solution (day 9)
challenge: 0.5 ml of 10% p-isopropylphenyl isocyanate solution (day 15)

No. of animals per dose:

10 males and 10 females

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 ml of 10% p-isopropylphenyl isocyanate solution

No. with + reactions:

20

Total no. in group:

20

Clinical observations:

pronounced erythema and oedema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 ml of 10% p-isopropylphenyl isocyanate solution. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: pronounced erythema and oedema.

Within 48 hours after the challenge all treated animals (20 guinea pigs) revealed a pronounced erythema and oedema. The control animals (5 male and 5 female guinea pigs) had no skin reactions.

Interpretation of results:

sensitising

Remarks:

Migrated information

Executive summary:

10 males and 10 females received a single intradermal induction with 0.1 ml of a 0.5 % solution of substance in paraffin simultaneous with Freunds complete adjuvans. On day 8 the animals were treated with a 10% solution of sodium laurylsulfate. On day 9 the animals received another dermal induction with 0.5 ml of a 10 % solution of test substance (occlusive application). Challenge was done 15 days after the dermal induction with 0.5 ml of a 10% solution (24 h occlusive). As a result p-isopropylphenyl isocyanate was classified as highly sensitizing.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The sensitisation potential of p-isopropylphenyl isocyanate was evaluated in the guinea-pig by intradermal route and cutaneous application, according to the maximisation method of Magnusson and Kligman. A positive result was found under the experimental conditions.

Migrated from Short description of key information:
maximisation test equivalent to guideline
result: substance is strong sensitising

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

T Due to regulation 67/548/EEC isocyanates have to be classified as respiratory sensitisers with R 42. Based on comparative analysis regarding studies on skin sensitisation with other isocyanates (p-isopropylphenylisocyanate_CAS 31027-31-3, n-butylisocyanante_CAS 111-36-4, 3,4-dichlorphenylisocyanante_CAS 102-36-3, 3,5-dichlorphenylisocyanate_CAS 28479-22-3, phenylisocyanate_CAS 103-71-9, trifluormethoxyphenylisocyanate_CAS 35037-73-1) which all have strong skin sensitisation properties, monoisocyanates without reliable studies will be additionally classifified with R43.

According RL 1272/2008/EG (GHS) a classification as Skin Sens.1A (H 317: May cause an allergic skin reaction) is warranted, based on comparative analysis regarding other isocyanates isocyanates (p-isopropylphenylisocyanate_CAS 31027-31-3, n-butylisocyanante_CAS 111-36-4, 3,4-dichlorphenylisocyanante_CAS 102-36-3, 3,5-dichlorphenylisocyanate_CAS 28479-22-3, phenylisocyanate_CAS 103-71-9, trifluormethoxyphenylisocyanate_CAS 35037-73-1 are all strong sensitisers, classified as Skin Sens. 1A). No classification for respiratory sensitisation is necessary (see discussion below).

There are no data on respiratory sensitization available. p-tolyl isocyanate is a monoisocyanate. The UK Health and Safety Commission Working Group on the Assessment of Toxic Chemicals, Working Group on Action to Control Chemicals concluded performed an assessment of the potential for isocyanic acid and other monoisocyanates to cause respiratory irritation and sensitization (WATCH Committee Paper WATCH/2008/4, 17 Jun., 2008; http://www.hse.gov.uk/aboutus/meetings/iacs/acts/watch/170608/p4.pdf) and came to the following conclusion: “With the exception of methyl isocyanate, information on the toxicity of the monoisocyanates is sparse. There is no direct evidence that any of the monoisocyanates can cause respiratory sensitisation. … However, this indirect information on the allergenicity and immunoreactivity of the monoisocyanates is very limited, and insufficient to reliably inform on their potential to cause respiratory sensitisation.” A similar conclusion was drawn by the German MAK commission concerning the monoisocyanates in 2009 (MAK- und BAT-Werteliste 2009).

 

In addition it should be also mentioned that the ‘default’ assumption of the former EU hazard classification systems that all isocyanates have the potential to cause respiratory sensitisation is not in agreement with the strategy for evaluating respiratory sensitisation data in the Technical Guidance Document (TGD) on information requirements for REACH (R.7a; page 256ff). The TGD proposes that, in the absence of specific health effects data, only diisocyanates that also meet the criteria for classification for skin sensitisation are presumed to be respiratory sensitisers.

Migrated from Short description of key information:
no data

Justification for classification or non-classification

The compound will be classified Skin Sens 1A (H317; may cause an allergic skin readion)

Due to regulation 67/548/EEC isocyanates have to be classified as respiratory sensitisers with R 42. Based on comparative analysis regarding studies on skin sensitisation with other isocyanates (p-isopropylphenylisocyanate_CAS 31027-31-3, n-butylisocyanante_CAS 111-36-4, 3,4-dichlorphenylisocyanante_CAS 102-36-3, 3,5-dichlorphenylisocyanate_CAS 28479-22-3, phenylisocyanate_CAS 103-71-9, trifluormethoxyphenylisocyanate_CAS 35037-73-1) which all have strong skin sensitisation properties, monoisocyanates without reliable studies will be additionally classifified with R43.

According RL 1272/2008/EG (GHS) a classification as Skin Sens.1A (H 317: May cause an allergic skin reaction) is warranted, based on comparative analysis regarding other isocyanates isocyanates (p-isopropylphenylisocyanate_CAS 31027-31-3, n-butylisocyanante_CAS 111-36-4, 3,4-dichlorphenylisocyanante_CAS 102-36-3, 3,5-dichlorphenylisocyanate_CAS 28479-22-3, phenylisocyanate_CAS 103-71-9, trifluormethoxyphenylisocyanate_CAS 35037-73-1 are all strong sensitisers, classified as Skin Sens. 1A). No classification for respiratory sensitisation is necessary (see discussion).