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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation: Similar to OECD 406; Guinea pig; 24h and 48h 15/15 animal responded to the 1% intradermal induction

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
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
A Guinea Pig Maximization Test according Magnusson and Kligman was performed on male guinea pigs to determine whether the test substance exhibits skin-sensitizing properties.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The LLNA method was not available.
Species:
guinea pig
Strain:
other: Pirbright white W 58
Sex:
male
Route:
intradermal and epicutaneous
Vehicle:
other: acetone/oil
Concentration / amount:
Intradermal induction: 1.0 %
Topical induction: 12 %
Challenge: 6 %


Topical induction: 5% (=25 mg test substance/ animal)
Challenge: 3% (=15 mg test substance/ animal)
Route:
epicutaneous, semiocclusive
Vehicle:
other: acetone/oil
Concentration / amount:
Intradermal induction: 1.0 %
Topical induction: 12 %
Challenge: 6 %


Topical induction: 5% (=25 mg test substance/ animal)
Challenge: 3% (=15 mg test substance/ animal)
No. of animals per dose:
15 animals (test and control group)
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
not measured/tested
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
not measured/tested
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
6 %
No. with + reactions:
15
Total no. in group:
15
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
6 %
No. with + reactions:
15
Total no. in group:
15
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
15
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
15

A clear evidence for a sentitising effect of 4-trifluoromethoxyphenyl isocyanate was found in the GPMT

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Remarks:
Based on EU GHS criteria
Conclusions:
4-Trifluoromethoxyphenyl isocyanate showed sensitising results.
Executive summary:

The Guinea Pig Maximization test was performed similarly to OECD Guideline 406 on male guinea pigs. 4-Trifluoromethoxyphenyl isocyanate showed sensitising results.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The Guinea Pig Maximization test was performed similarly to OECD guideline 406 on male guinea pigs. 4-Trifluoromethoxyphenyl isocyanate showed sensitising results.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

According Regulation (EC) No 1272/2008 (CLP) 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.


 

Justification for classification or non-classification

According to the classification criteria outlined in the section 3.4.2.2.3.2. (Guidance on the Application of CLP criteria, 2012), substance is classified as Category 1A 'skin sensitizer'.