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Description of key information

- study conducted according to OECD 406, GLP, himalayan guinea pigs were intradermally and epicutaneous exposed to MDAB at concentrations of 3% and 25%, respectively for induction and 15% and 25% test material in acetone/bi-distilled water 1:1 for challenge, not sensitizing , read-across

- study conducted according to OECD 406, GLP, Dunkin-Hartley guinea pigs were intradermally and epicutaneously exposed to 0.1% (w/v) for induction and with 10% (w/w) for challenge, senitizing, read-across

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:
weight of evidence
Study period:
1989-11-20 to 1990-04-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
12 May, 1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
According to Annex XI section 1.1.2. of Regulation (EC) No 1907/2006 (REACH) testing of skin sensitisation in an in vivo LLNA is not necessary if there are data that is generated by studies not carried out according to GLP or the test methods reffered to in Article 13 (3) of the same regulation if the data is sufficcient for the purpose of classification and labelling and/or risk assessment, if the key parameters foreseen to be investigated in the recommended methods are reliably covered, the exposure duration is similar to that of the recommended methods and if the study is adequate and reliable documented. The present GPMT was conducted according to OECD guideline 406, which is reliable without restrictions and adequate for classification and labelling purposes. It is well documented, measures the recommended key parameters and exposure duration is comparable to an in vivo LLNA. Thus, due to the provided reliable and adequate data the perfomance of an in vivo LLNA is not necessary. Furthermore, the study was conducted prior to regulatory implementation of the LLNA method.
Species:
guinea pig
Strain:
Himalayan
Remarks:
spotted
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 7 weeks, females 8 weeks
- Weight at study initiation: males 357-405 g, females 345-384 g
- Housing: individually in Makrolon type-3 cages with standard soft wooding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet: ad libitum, pelleted standard Kiba 342, Batch 55/89 guinea pig breeding/maintenance diet ("Kliba", Klingentalmühle AG, CH-4303 Kaiseraugst)
- Water: ad libitum, Community tap water from Itingen
- Acclimation period: one week under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: Acetone/bi-distilled water 1:1
Concentration / amount:
intradermal injections: 3% in acetone/bi-distilled water, epicutaneous: 25% in acetone/bi-distilled water
Day(s)/duration:
intradermal: single injection followed by epicutaneous application after 7 days; epicutaneous: 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
other: Acetone/bi-distilled water 1:1
Concentration / amount:
left flank 15%, right flank 25%
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Ten animals (5 males, 5 females) were treated as control group and twenty animals (10 males, 10 females) were treated at test group.
Details on study design:
Preliminary study:
Intradermal injections (0.1 mL/site) were made into the clipped flank of two guinea-pigs at concentrations of 5% (right flank), 3%, 1% and 0.5%
(left flank) of the test article in acetone/bi-distilled water 1:1. The resulting dermal reactions were assessed 24 hours later.
Epidermal applications:
Patches of filter paper (2 x 2 cm) were saturated with concentrations of 25%, 15%, 10% and 5% of the test article in acetone/bi-distilled water 1:1 and applied to the clipped and shaved flanks of each of four guinea-pigs. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wrapped around the trunk and covered with impervious adhesive tape. This procedure ensured the intensive contact of the test articleeven if it is insoluble in the vehicle used. The dressings were removed after an exposure period of 24 hours·and the reaction sites were assessed for erythema and edema on a numerical basis according to the scale described above. Further examination of the sites were performed 24 and 48 hoursafter removal of the dressings. Prior to the first reading, the epidermal application sites were gently washed off excess test article with acetone.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: One intradermal application, one epicutaneous application
- Exposure period: Intradermal: single injection followed by epicutaneous application after one week
- Test groups: Intradermal: 1) Freund´s complete adjuvant 50:50 with bi-distilled water 2) The test article, diluted to 3% with acetone/bi-distilled water 1:1 3) The test article at the concentration used in (2), emulsified in a 50:50 mixture of Freund´s adjuvant and the vehicle used in (2). Epicutaneous: A 2 x 4 cm patch of filter paper saturated with the test article (25% in acetone/bi-distilled water 1:1) placed over the injection sites
- Control group: The control groups were treated according to the test groups with the omission of the test article.
- Site: dorsal skin from the scapular region
- Frequency of applications: Once
- Duration: Intrdermal: single injection followed by epicutaneous application after one week
- Concentrations: Intradermal: 3% with acetone/bi-distilled water 1:1, Epicutaneous: 25% in acetone/bi-distilled water 1:1

B. CHALLENGE EXPOSURE
- No. of exposures: one epicutaneous application of two concentrations
- Day(s) of challenge: day 21
- Exposure period: 24 h
- Test groups: Two patches (2 x 2 cm) of filter paper were saturated with a) non-irritant concentration (15% in acetone/bi-distilled water 1:1) of the test article and b) with the acetone/bi-distilled water 1:1 only and applied to the left flank, the right flank was treated with 25% in acetone/bi-distilled water 1:1.
- Control group: Treated the same way as unter Test groups
- Site: scapular region
- Evaluation (hr after challenge): immediately, 24h and 48h after removal of the patches
Challenge controls:
The control animals were treated in the same way as described above.
Positive control substance(s):
yes
Remarks:
Formaldehyde-solution, 20% dilution in bi-distilled water for induction, 15% dilution for challenge
Positive control results:
9/10 animals induced and challenged with formaldehyde-solution showed positive reactions.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0%; challenge: 15% in acetone/bi-distilled water (1:1)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction: 0%; challenge: 15% in acetone/bi-distilled water (1:1)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
intradermal induction: 3% in acetone/bi-distilled water (1:1); epicutaneous induction: 25% in acetone/bi-distilled water (1:1); challenge: 15% in acetone/bi-distilled water (1:1)
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
no indication of skin sensitisation
Remarks:
1 female animal was killed due to ethical reason on day 10 of the study
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
intradermal induction: 3% in acetone/bi-distilled water (1:1); epicutaneous induction: 25% in acetone/bi-distilled water (1:1); challenge: 15% in acetone/bi-distilled water (1:1)
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
no indication of skin sensitisation
Remarks:
1 female animal was killed due to ethical reason on day 10 of the study
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
induction 20% HCHO in bi-distilled water; challenge 15 % HCHO in bi-distilled water
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
induction 20% HCHO in bi-distilled water, challenge 15% HCHO in bi-distilled water
No. with + reactions:
4
Total no. in group:
9
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, no allergenic potency of the test article was concluded. The results were interpreted according to the rating of Magnusson and Kligman (1970). According to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS), this test article is considered to be not a sensitizer and thus, does not need to be classified.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1990-10-31 to 1990-12-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
not reported
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
not reported
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid GPMT conducted according to guideline is available, which is reliable without restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new Annex of the REACH Regulation entered into force.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation:8-12 weeks
- Weight at study initiation: 300-376g
- Housing:The animals were housed in groups of up to three in solid floor polypropylene cages
- Diet (e.g. ad libitum): ad libitum, mains tap water
- Water (e.g. ad libitum): ad libitum, Guinea pig diet, Special Diet Services Limited, Witham, Essex, U.K.
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 46-67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Remarks:
B.P.
Concentration / amount:
0.1% (w/v)
Day(s)/duration:
9
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Remarks:
B.P.
Concentration / amount:
10% (w/w)
Day(s)/duration:
1
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
Selection of concentration for intradermal injection: Four animals were intradermally injected with 5%, 1%, 0.5% and 0.1% (w/v) preparations of the test material in arachis oil BP. The highest concentration that did not cause local necrosis, ulceration or systemic toxicity, was selscted for the intradermal induction stage of the main study (i.e.: 0.1%).
Selection of concentration for topical induction: Two guinea pigs (intrdermally injected with Freund´s Complete Adjuvant seven days earlier) were treated with 50%, 25%, 10% and 5% (w/w) preparations of the test material in arachis oil BP. The highest practical concentration producing only mild to moderate dermal irritation after 48-hour occlusive exposure, was selected for the topical induction stage of the main study (i.e.: 50%).
Selection of concentrations for topical challenge: 50%, 25%, 10% and 5% (w/w) preparations of the test material in arachis oil BP were applied occlusively to the flanks of two guinea pigs for a period of 24 h. These guinea pigs had been treated identically to the control animals of the main study, up to day 14. The maximum practical non-irritant concentration of the test material was selscted for the topical challenge stage of the main study (i.e.: 10%).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 9 days
- Test groups: FCA + distilled water 1:1; 0.1% (w/v) solution of the test material in arachis oil BP; 0.1% (w/v) solution of the test material in a 1:1 preparation of FCA + arachis oil BP
- Site: shoulder region, 40 mm x 60 mm area
- Frequency of applications: intradermal injection and 7 days after injection topical induction for 48h
- Concentrations: Intradermal injection with 0.1% (w/v) suspension of test material in arachis oil B.P, topical application with 50% (w/w) solution in arachis oil B.P.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24h
- Test groups: 10% test material in arachis oil BP (w/w) on the right flank
- Control group: vehicle alone on the left flank
- Site: shoulder region, 40 mm x 60 mm area
- Concentrations: 10% (w/w) suspension of test substance in arachis oil B.P.
- Evaluation (hr after challenge): 1h, 24h, 48h and 72h

Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% (w/w)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10% (w/w)
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
In the present study conducted according to OECD guideline 406, thirty female guinea pigs were exposed to intradermal and topic induction with either 0.1% (w/v) or 50% (w/w) Compimide 183 in arachis oil (topic induction 1 week). after 14 days of recovery the animals were exposed to 10%(w/w) test item topically and the skin reactions were recorded at 1h, 24h, 48 and 72h. All animals from the test group exhibited an extented reaction site and edema after 24h. After 48h desquamation occurred and the adverse reactions actually prevent the evaluation of erythema after 72 h. Thus, the substance is considered to be sensitizer and is classified into Category 1 A according to Regulation (EC) No 1272/2008 (CLP) and the globally harmonized system for classificagtion of chemicals (GHS).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No experimental data on skin sensitisation are available for the target substance Compimide 183. However, reliable data from skin sensitisation studies conducted with the closely related source substances MDAB and ABH are available. A justification for read-across is given in IUCLID section 13

Skin Sensitisation:

In a skin sensitisation study conducted according to OECD guideline 406, 20 Himalayan guinea pigs were exposed to MDAB using the method of Magnusson and Kligman. Further 10 animals were used for the control group. Positive control substance was Formaldehyde-solution, 20% dilution in bi-distilled water. The animals were exposed intradermally and epicutaneously to 3 % (w/w), single exposure, or 25 % (w/w) solution of the test substance, exposure period of 48 h, respectively. 14 days after the induction procedure the animals were challenged for 24 h with 15 % and 25% (w/w) solution of the test substance applied epicutaneously. The test item was applied in acetone/bi-distilled water (1:1) as solvent. The reading timepoints were 24 h and 48 h after end of the exposure. None of the animals showed any indication of sensitisation.

In this study MDAB is not considered to be a sensitizer.

In a supporting study conducted according to OECD guideline 406, thirty female guinea pigs were exposed to intradermal and topic induction with either 0.1% (w/v) or 50% (w/w) MDAB in arachis oil (topic induction 1 week). After 14 days of recovery the animals were exposed to 10%(w/w) test item topically and the skin reactions were recorded at 1h, 24h, 48 and 72h. All animals from the test group exhibited an extented reaction site and edema after 24h. After 48h desquamation occurred and the adverse reactions actually prevent the evaluation of erythema after 72 h.

Thus, MDAB is considered to be sensitizer.

Under the conditions of the study conducted according to OECD guideline 406, no allergenic potency of MDAB was concluded. The results were interpreted according to the rating of Magnusson and Kligman (1970). According to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS), this test article is considered to be not a sensitizer and thus, does not need to be classified.

In a study conducted according to OECD guideline 406, thirty female guinea pigs were exposed to intradermal and topic induction with either 0.1% (w/v) or 50% (w/w) MDAB in arachis oil (topic induction 1 week). after 14 days of recovery the animals were exposed to 10%(w/w) test item topically and the skin reactions were recorded at 1h, 24h, 48 and 72h. All animals from the test group exhibited an extented reaction site and edema after 24h. After 48h desquamation occurred and the adverse reactions actually prevent the evaluation of erythema after 72 h. Thus, the substance is considered to be sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available results for the structurally similar substance MDAB and because the final product of Compimide 183 still contains 50% free MDAB, Compimide is considered to be a senitizer and classified 'Category 1A' according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) for precautionary reasons.