Registration Dossier

Administrative data

Description of key information

There are 4 studies available that address skin sensitisation properties of XDI. Two studies have Klimisch score 1 and two have Klimisch score 2. As all these reliable studies showed a clear positive response in sensitisation (all animals were sensitised), no specific study is selected.

Based on these results, XDI is considered to be a skin sensitiser (sub-category 1A).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
February/March 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older study but performed according to guinea pig maximization test as described by Magnusson and Kligman, comparable to OECD/EC test guidelines. Purity and batch number not given.
Justification for type of information:
The study was performed before non-animal tests or the local lymph node assay were available.
Principles of method if other than guideline:
Guinea pig maximization test as described by B. Magnusson and A.M. Kligman (1970) in 'Allergic Contact Dermatitiis in the Guinea-pig: identification of contact allergens'
GLP compliance:
no
Remarks:
study performed before GLP introduction
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Route:
intradermal and epicutaneous
Vehicle:
other: Alembicol D
Concentration / amount:
Based on irritancy of a range of dilutions, the maximum concentration suitable for intradermal injection was found to be 0.01% v/v and for topical application as supplied. 20% v/v in acetone was selected for challenge.
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Concentration / amount:
Based on irritancy of a range of dilutions, the maximum concentration suitable for intradermal injection was found to be 0.01% v/v and for topical application as supplied. 20% v/v in acetone was selected for challenge.
No. of animals per dose:
10 test and 5 control animals
Positive control substance(s):
no
Reading:
other: reading 24-72 hours after challenge
Group:
test chemical
Dose level:
20%
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
One animal showed equivocal results. One animal showed localised dermal reaction, several animals showed dryness and sloughing of the epidermis which in one animal was accompanied by thickening of the epidermis obscuring erythema.
Remarks on result:
other: see Remark
Remarks:
Reading: other: reading 24-72 hours after challenge. Group: test group. Dose level: 20%. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: One animal showed equivocal results. One animal showed localised dermal reaction, several animals showed dryness and sloughing of the epidermis which in one animal was accompanied by thickening of the epidermis obscuring erythema. .
Reading:
other: reading 24-72 hours after challenge
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
One animal showed localised dermal reaction at 24 hours, several animals showed dryness and sloughing of the epidermis.
Remarks on result:
other: see Remark
Remarks:
Reading: other: reading 24-72 hours after challenge. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: One animal showed localised dermal reaction at 24 hours, several animals showed dryness and sloughing of the epidermis..
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
1,3-bis (isocyanatomethyl)benzene produced evidence of delayed contact hypersensitivity in 9/10 guinea pigs. Classification with risk phrase R43 is warranted.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 March-18 April 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The study was performed before non-animal tests or the local lymph node assay were available.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
other: Magnusson, B. and Kligman, AM (1970). Allergic Contact Dermatitis in the guinea pig: identification of contact allergens, Thomas, CC Springfield, Illinois, USA
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed before the LLNA was available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, UK
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 451 to 524 g
- Housing: animals were housed in groups of five in suspended metal cages with mesh floors.
- Diet (e.g. ad libitum): ad libitum (Vitamin C enriched guinea pig diet FD2)
- Water (e.g. ad libitum): ad libitum
- Acclimatisation period: twelve days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5-21
- Humidity (%): 24-61
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: Alembicol D
Concentration / amount:
Preliminary study:
For Intradermal concentrations 0.001%, 0.0025%, 0.005%, 0.01%, 0.025%, 0.05%, and 0.1% v/v
For Topical concentrations: 0.5%, 1%, 2.5%, 5%, 7.5%, 10%, 15% and 20%, 30%, 50%, 70%, 100% v/v
Main study:
Intradermal injection: 0.01% v/v (highest concentration in preliminary study, causing irritation but not adversely affecting the animals)
Topical application: 100%
Challenge application: 15 and 7.5% v/v (15% was the highest concentration not giving rise to irritating effects)
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Concentration / amount:
Preliminary study:
For Intradermal concentrations 0.001%, 0.0025%, 0.005%, 0.01%, 0.025%, 0.05%, and 0.1% v/v
For Topical concentrations: 0.5%, 1%, 2.5%, 5%, 7.5%, 10%, 15% and 20%, 30%, 50%, 70%, 100% v/v
Main study:
Intradermal injection: 0.01% v/v (highest concentration in preliminary study, causing irritation but not adversely affecting the animals)
Topical application: 100%
Challenge application: 15 and 7.5% v/v (15% was the highest concentration not giving rise to irritating effects)
No. of animals per dose:
10 test and 5 control
Details on study design:
RANGE FINDING TESTS: Selection of concentrations for main study
Intradermal induction: 0.001%, 0.0025%, 0.005%, 0.01%, 0.025%, 0.05% and 0.1% were injected. The highest concentration causing only mild to moderate skin irritation, and which was well tolerated systemically was selected for intradermal induction.
Topical induction: 0.5%, 1%, 2.5%, 5%, 7.5%, 10%, 15%, 20%, 30%, 50%, 70% and 100% was applied, highest concentration producing only mild to moderate dermal irritation was selected.
Topical challenge: 15%, 7.5% were applied occlusively for a period of 24 hours. The highest non irritant concentration and one lower concentration were selected for the topical challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three injections, 0.1 ml each: Freund's Complete Adjuvant plus water in ratio 1:1, a 0.01% v/v formulation of the test substance in Alembicol D, a 0.01% v/v formulation of the test substance in a 50:50 mixture of Freund's Complete Adjuvant plus Alembicol D.
- Exposure period: One week later Day 7, same region was clipped again and treated with a topical application (0.4 ml) of a paper saturated with the undiluted test material. An occlusive dressing was kept in place for 48 hours.
- Control group: Identical procedure as test animals, except test substance was omitted.
- Site: 40x60 mm area, hair was removed on the shoulder region
- Duration: 21 days

B. CHALLENGE EXPOSURE
- Day(s) of challenge: Day 21, two weeks after topical induction.
- Exposure period: A filter paper saturated with approx. 0.2 ml of 15% v/v test substance was applied to an anterior site of the flank. A filter paper saturated with 7.5% v/v test substance was applied to the posterior site. Patches were occluded. After 24 hours of occlusive dressing this was removed.
- Control group: All animals were treated the same.
- Site: An area on left flank of each animal was clipped free of hair.
- Evaluation (hr after challenge): 24 + 48 after removal of dressing
Positive control substance(s):
yes
Remarks:
periodically checked with known sensitisers, hexyl cinnamic aldehyde (HCA), benzocaine and 2-mercaptobenzothiazole (MBT)
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
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
7.5% and 15%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Same results at 48 hours. Necrosis occured in one animal, necrotic patch in several animals, thickening, dryness and sloughinig of the epidermis occured also in one animal.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 7.5% and 15%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Same results at 48 hours. Necrosis occured in one animal, necrotic patch in several animals, thickening, dryness and sloughinig of the epidermis occured also in one animal. .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
7.5% and 15%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Same results at 48 hours. No observations.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 7.5% and 15%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: Same results at 48 hours. No observations..

No signs of ill health or toxicity were noted. Bodyweight increases in test group animals were comparable to control group animals. During induction, slight irritation was seen in test and control animals after intradermal injections, slight erythema was observed after topical application in test and control animals.

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
Takenate 500 produced evidence of skin sensitisation (delayed contact hypersensitivity) in all of the ten test animals. Classification with risk phrase R43 is warranted.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 June-18 July 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The study was performed before non-animal tests or the local lymph node assay were available.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed before the LLNA was available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation:8-12 weeks
- Weight at study initiation: 300-390 g
- Housing: in groups of up to three in solid floor polypropylene cages furnished with softwood shavings.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 48-68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Sighting study:
For intradermal induction, 0.1%, 0.5%, 1%, 5% w/v; for topical induction, 10%, 25%, 50% and 75% v/v; for topical challenge, 25%, 50% and 75% v/v
Based on the results of the sighting study the following concentrations for the main study were selected:
Intradermal induction: 0.1% (w/v), however no evidence of irritation was seen at this concentration, while irritation was observed at 0.5%
Topical induction 75% (v/v)
Topical challenge 75% and 50% (v/v)
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Sighting study:
For intradermal induction, 0.1%, 0.5%, 1%, 5% w/v; for topical induction, 10%, 25%, 50% and 75% v/v; for topical challenge, 25%, 50% and 75% v/v
Based on the results of the sighting study the following concentrations for the main study were selected:
Intradermal induction: 0.1% (w/v), however no evidence of irritation was seen at this concentration, while irritation was observed at 0.5%
Topical induction 75% (v/v)
Topical challenge 75% and 50% (v/v)
No. of animals per dose:
20 test and 10 control
Details on study design:
RANGE FINDING TESTS: Selection of concentrations for main study
Intradermal induction: 0.1%, 0.5%, 1% and 5% were injected. The highest concentration that did not cause local necrosis, ulceration or systemic toxicity was selected for intradermal induction.
Topical induction: 10%, 25%, 50% and 75% was applied, highest concentration producing only mild to moderate dermal irritation after a 48 hr occlusive exposure was selected.
Topical challenge: 100%, 75%, 50% and 25% were applied occlusively for a period of 24 hours. The highest non irritant concentration was selected for the topical challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three injections, 0.1 ml each: Freund's Complete Adjuvant plus distilled water in ratio 1:1, a 0.1% w/v formulation of the test material in arachis oil BP, a 0.1% w/v formulation of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus arachis oil BP.
- Exposure period: One week later Day 7, same region was clipped again and treated with a topical application of 75% test material which was applied on filter paper, which was kept in place for 48 hours (occlusive dressing). Degree of erythema was quantified 1 and 24 hours following removal of the patches.
- Control group: Identical procedure as test animals, 2nd and 3rd intradermal injections consisted of arachis oil BP, subsequently Freund's Complete Adjuvant and arachis oil BP in the ratio 1:1. Topical applications also same procedure except that vehicle was applied to filter paper.
- Site: 40x60 mm area, hair was removed on the shoulder region
- Duration: 21 days

B. CHALLENGE EXPOSURE
- Day(s) of challenge: Day 21
- Exposure period: A filter paper with 75% test material was applied on the right flank, a filter paper with 50% test material was applied to a separate site on the right skin site. Patches were occluded. After 24 hours, dressing removed, challenge sites swabbed.
- Control group: All animals were treated the same.
- Site: An area of 50x70 mm on both flanks of each animal was clipped free of hair with veterinary clippers.
- Evaluation (hr after challenge): 24 + 48 after dressing removal
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene (DNCB)
Positive control results:
A summary of a positive control substance was included. Experiment dated December 1991, in which DNCB produced a 89% (16/18) sensitisation rate.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75% and 50%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
Scattered mild redness, small areas of grey-coloured dermal necrosis, slight to well defined oedema, loss of skin elasticity and desquamation, small superficial scattered scabs and hardened dark brown/black-coloured scab. Comparable results at 48 hrs.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75% and 50%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: Scattered mild redness, small areas of grey-coloured dermal necrosis, slight to well defined oedema, loss of skin elasticity and desquamation, small superficial scattered scabs and hardened dark brown/black-coloured scab. Comparable results at 48 hrs..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75% and 50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Scattered mild redness was noted of 4 (50%) and 8 (75%) control animals at 24 hr, and in 1 (50%) and 3 (75%) control animal at 48 hr.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75% and 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Scattered mild redness was noted of 4 (50%) and 8 (75%) control animals at 24 hr, and in 1 (50%) and 3 (75%) control animal at 48 hr..

Bodyweight gains in the test group and control group were comparable.

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
XDI produced a 100% (20/20) sensitisation rate and was classified as an extreme sensitiser to guinea pig skin. Classification with risk phrase R43 is warranted.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 January 1998 - 21 March 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The study was performed before non-animal tests or the local lymph node assay were available.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed before the LLNA was available.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 338 to 426 g
- Housing: animals were housed singly or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum (Guinea Pig FD1 Diet, Special diets services limietd, Witham, Essex, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimatisation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 37-58
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Remarks:
BP
Concentration / amount:
Sighting tests:
For Intradermal induction concentrations 0.01%, 0.05%, 0.1%, 0.5%, 1% and 5% w/v
For Topical induction concentration 25%, 50%, 75%, 100% v/v
For Topical challenge concentration 25%, 50%, 75% and 100% v/v
Main test:
Intradermal induction: 0.01% w/v in arachis oil BP, 0.01% w/v in a mixture of Freund's complete adjuvant plus distilled water (1:1)
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied and 75% v/v in arachis oil BP
Topical rechallenge: 50% and 25% v/v in arachis oil BP
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Remarks:
BP
Concentration / amount:
Sighting tests:
For Intradermal induction concentrations 0.01%, 0.05%, 0.1%, 0.5%, 1% and 5% w/v
For Topical induction concentration 25%, 50%, 75%, 100% v/v
For Topical challenge concentration 25%, 50%, 75% and 100% v/v
Main test:
Intradermal induction: 0.01% w/v in arachis oil BP, 0.01% w/v in a mixture of Freund's complete adjuvant plus distilled water (1:1)
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied and 75% v/v in arachis oil BP
Topical rechallenge: 50% and 25% v/v in arachis oil BP
No. of animals per dose:
Main test: 10 test and five control animals were used
Details on study design:
RANGE FINDING TESTS: Selection of concentrations for main study
Intradermal induction: 0.01%, 0.05%, 0.1%, 0.5%, 1% and 5% were injected. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically was selected for intradermal induction.
Topical induction: 25%, 50%, 75% and 100% was applied, highest concentration producing only mild to moderate dermal irritation was selected.
Topical challenge: 100%, 75%, 50% and 25% were applied occlusively for a period of 24 hours. The highest non irritant concentration and one lower concentration were selected for the topical challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three injections, 0.1 ml each: Freund's Complete Adjuvant plus distilled water in ratio 1:1, a 0.01% w/v formulation of the test material in arachis oil BP, a 0.01% w/v formulation of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.
- Exposure period: 24 and 48 hours after intradermal injection degree of erythema was evaluated. One week later Day 7, same region was clipped again and treated with a topical application of the undiluted test material. An occlusive dressing, including a filter paper saturated with undiluted test material, was kept in place for 48 hours. Degree of erythema was quantified 1 and 24 hours following removal of the patches.
- Control group: Identical procedure as test animals, 2nd and 3rd intradermal injections consisted of arachis oil BP, subsequently a 50% w/v formulation of arachis oil BP in Freund's Complete Adjuvant/distilled water 1:1. Topical applications also same procedure except nothing was applied to filter paper.
- Site: 40x60 mm area, hair was removed on the shoulder region
- Duration: 21 days

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge: Day 21
- Exposure period: A filter paper saturated with the undiluted test material on the right flank a filter paper saturated with 75% v/v test material was applied to the left skin site. Patches were occluded. After 24 hours, dressing removed, challenge sites swabbed.
- Control group: All animals were treated the same.
- Site: An area of 50x70 mm on both flanks of each animal was clipped free of hair with veterinary clippers.
- Evaluation (hr after challenge): 24 + 48 after dressing removal

C. RECHALLENGE
- 20 days after original challenge, animals (test and control) were re-challenged on previously untreated areas of skin using 50% and 25% test material.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole
Positive control results:
A summary of positive control data fro the Magnusson and Kligman Maximisation study was included. Last result is from November 1997 restulting in 90% incidence of sensitisation.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50 and 25%
No. with + reactions:
8
Total no. in group:
8
Clinical observations:
Same results 48 hours after challenge. One animal found dead on Day 8 and one animal killed for humane reasons on Day 10.
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50 and 25%. No with. + reactions: 8.0. Total no. in groups: 8.0. Clinical observations: Same results 48 hours after challenge. One animal found dead on Day 8 and one animal killed for humane reasons on Day 10. .
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
50 and 25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Same results 48 hours after challenge. Two animals showed physical damage caused during dressing removal.
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 and 25%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: Same results 48 hours after challenge. Two animals showed physical damage caused during dressing removal..

After challenge, both in test as well as the control group, very slight to well defined erythema were noted at the challenge sites sometimes together with very sligh oedema.

At 50%: After re-challenge very slight erythema was noted in one animal of the control group. Positive oedema responses were noted at challenge sites of all test group animals at the 24-h observation and five test group animals at the 48-h observation (erythema could not be scored due to adverse reactions). At 25%: no skin reactions were noted in the control group. Positive skin responses were noted at the challenge site of all animals at 24 hr observation and in 7/8 animals at 48 hr observation.

Bodyweight gains in test group were comparable to control group animals.

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
XDI produced a 100% (8/8) sensitisation rate and was classified as an extreme sensitiser to guinea pig skin. According to EU labelling regulations: Xi and R43.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Four skin sensitisation studies, all according to Magnusson and Kligman, have been performed of which three have been performed according to OECD test guideline 406 and GLP principles. Different concentrations were used for induction and challenge, ranging from 0.1 -0.01% for induction, 75 -100% for topical induction and 7.5 -100% for topical challenge. When challenged with 75 -100% substance, also the control animals showed irritation resulting in rechallenge with a 25 -50% solution. All studies showed a clear positive response in sensitisation, all animals were sensitised. Positive and negative controls showed the validity of the study. Therefore, XDI is considered to be a skin sensitiser (sub-category 1A).

Respiratory sensitisation

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

In accordance with the ECHA Guidance document "Guidance on information requirements and chemical safety assessment, Chapter R.7a: Endpoint specific guidance"of May 2008 (page 258 - 290), 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. The available data does not show that such a classification is not warranted for XDI.

Justification for classification or non-classification

Skin sensitisation

Based on the available studies, XDI is classified according to the CLP Regulation (EC) No. 1272/2008 with Cat.1A, H317 "May cause an allergic skin reaction".

Respiratory sensitisation

As XDI is a diisocyanate, XDI is classified according to the CLP Regulation (EC) No. 1272/2008 and ECHA Guidance with Cat. 1, H317 "May cause allergy or asthma symptoms or breathing difficulties if inhaled".