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Registration Dossier
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EC number: 942-422-6 | CAS number: -
Endpoint summary
Administrative data
Description of key information
non-sensitising, Guinea Pig (male), eq. to OECD TG 406, 1978
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1978
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Pre-GLP study following a method equivalent to a recognised guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- Principles of method if other than guideline:
- Method employed in this study for the detection of delayed contact hypersensitivity was the guinea-pig maximization test described by B. Magnusson and A.M. Kligman (1970) in "Allergic Contact Dermatitis in the Guinea-Pig: Identification of contact allergens"; C.C. Thomas, USA.
- GLP compliance:
- no
- Remarks:
- In accordance with REACH Regulation (EC) 1907/2006: Annex XI: section 1.1.2 adequate and reliable (with restrictions) study information has been provided (not in accordance with GLP) but which can be considered equivalent to the relevant test method.
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- In accordance with REACH Regulation (EC) 1907/2006: Annex VII: column 2 as amended by Commission Regulation (EU) 2017/706, a well documented study report conducted before 10 May 2017, following a method equivalent or similar to guideline with acceptable deviations is available. This is sufficient to fulfil the standard information requirement in accordance with REACH Regulation (EC) 1907/2006: Annex XI: section 1.1.2 since adequate and reliable (with restrictions) study information has been provided suitable for classification and labelling and/or risk assessment.
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Recognised supplier
- Housing: Throughout the investigation the guinea-pigs were housed in a suspended cage with a wire mesh floor.
- Diet (e.g. ad libitum): vitamin-C enriched guinea pig pelleted diet ad libitum; hay once per week
- Water (e.g. ad libitum): tap water ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): Not reported - Route:
- intradermal and epicutaneous
- Vehicle:
- other: dipropylene glycol (DIPG) (10%) aqueous
- Concentration / amount:
- Preliminary irritation testing: intradermal: 1% (maximum non-irritating dose) ; topical: 100% (undiluted)
Induction:
- Intradermal: 1% test material
- Topical: 100% test material (undiluted)
- Challenge: 25% - Route:
- epicutaneous, occlusive
- Vehicle:
- other: dipropylene glycol (DIPG) (10%) aqueous
- Concentration / amount:
- Preliminary irritation testing: intradermal: 1% (maximum non-irritating dose) ; topical: 100% (undiluted)
Induction:
- Intradermal: 1% test material
- Topical: 100% test material (undiluted)
- Challenge: 25% - No. of animals per dose:
- Test group: 10
- Details on study design:
- RANGE FINDING TESTS:
Preliminary Investigations: The intradermal and topical irritancy of a range of dilutions of the test substance was investigated. The maximum concentration suitable for intradermal injection was found to be 1% v/v in 10% aqueous dipropylene glycol (DIPG), and for topical application to be undiluted test substance. These concentrations were subsequently utilised in the induction phase of the main study. A sub-erythemal concentration of test substance 25% v/v in DIPG was selected for the challenge application.
MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal induction: intradermal injections of a 1% v/v mixture of the test substance in 10% aqueous DIPG, a 1% v/v mixture of the test substance 10% aqueous DIPG 50:50 with Complete Freund's Adjuvant, and 50% aqueous Complete Freund's Adjuvant alone into the shaved 4x6 cm dorsal area of each of 10 guinea pigs.
Topical Application: Seven days after intradermal injections, the topical induction phase was conducted. Prior to the topical induction, the 4x6cm injection sites were clipped free of hair. A volume of 0.4 ml of undiluted test substance was spread over a 3 x 6 cm patch of Whatman No.3 MM paper. The patch was placed on the skin and covered by a 6 cm length of impermeable plastic adhesive tape (4 cm width "Blenderm"). This in turn was firmly secured by elastic adhesive bandage ("Elastoplast" 6.4 cm width) wound round the torso. The dressing was left in place for 48 hours.
B. CHALLENGE EXPOSURE
14 days after the induction period, Hair was removed with electric clippers from a 5 x 5 cm area on the left flank of each guinea pig. The test sample (0.1 ml) was applied to a 2 x 2 cm Whatman No, 3 MM paper in a similar fashion to that used for topical induction application. The patch was sealed to the flank for 24 hours under o 4 cm strip of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek" impervious plastic adhesive tape. The challenge site was evaluated 24, 48 end 72 hours after removal of the patch. The scoring system for responses was fully described within the study report. - Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- 1 test animal died prior to challenge; death was not considered as test substance related
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: 1 test animal died prior to challenge; death was not considered as test substance related.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- 1 test animal died prior to challenge
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: 1 test animal died prior to challenge.
- Reading:
- other: 3rd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- 1 test animal died prior to challenge
- Remarks on result:
- other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: 1 test animal died prior to challenge.
- Interpretation of results:
- GHS criteria not met
- Remarks:
- EU criteria not met
- Conclusions:
- Under the conditions of this study used, the test material is not considered to be a contact sensitizer.
- Executive summary:
The study was performed according to a method equivalent to guideline OECD TG 406 consistent with Magnusson-Kligman maximisation test to assess the skin sensitisation potential of the test substance. The study was conducted using a preliminary irritation screen, a two-stage induction phase and a challenge phase. Preliminary irritation testing was for use in the induction phases of the study and the challenge phase of the study. The first stage of the induction phase involved intradermal injections of a 1% v/v mixture of the test substance in 10% aqueous DIPG, a 1% v/v mixture of the test substance 10% aqueous DIPG 50:50 with Complete Freund's Adjuvant, and 50% aqueous Complete Freund's Adjuvant alone into the dorsal area of each of 10 guinea pigs. After 7 days the second stage of the induction phase entailed the topical application of the undiluted test substance onto the shaved dorsal area of the test group animals using occlusive dressings for 48 hours. 14 days after the induction period, a challenge dose of the test substance 25% v/v in DIPG was selected for the challenge application to the left flank on each test animal using the same procedure as in the topical induction. The site was inspected at 24, 48 and 72 hours for the presence of erythema and oedema. Under the conditions of this study, the test material is not considered to be a contact skin sensitizer.
Reference
Table 1. Dermal reactions elicited in challenge application
No. |
E/O scores |
24 hours |
48 hours |
72 hours |
Results (positive or negative) |
1 |
E O |
0 0 |
0 0 |
0 0 |
- |
2 |
E O |
0 0 |
0 0 |
0 0 |
- |
3 |
E O |
* |
* |
* |
N/A |
4 |
E O |
0 0 |
0 0 |
0 0 |
- |
5 |
E O |
0 0 |
0 0 |
0 0 |
- |
6 |
E O |
0 0 |
0 0 |
0 0 |
- |
7 |
E O |
0 0 |
0 0 |
0 0 |
- |
8 |
E O |
0 0 |
0 0 |
0 0 |
- |
9 |
E O |
0 0 |
0 0 |
0 0 |
- |
10 |
E O |
0 0 |
0 0 |
0 0 |
- |
* died prior to challenge; reported as not test substance related
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
eq. or similar to OECD TG 406, 1978: The study was performed according to a method equivalent to guideline OECD TG 406 consistent with Magnusson-Kligman maximisation test to assess the skin sensitisation potential of the test substance. The study was conducted using a preliminary irritation screen, a two-stage induction phase and a challenge phase. Preliminary irritation testing was for use in the induction phases of the study and the challenge phase of the study. The first stage of the induction phase involved intradermal injections of a 1% v/v mixture of the test substance in 10% aqueous DIPG, a 1% v/v mixture of the test substance 10% aqueous DIPG 50:50 with Complete Freund's Adjuvant, and 50% aqueous Complete Freund's Adjuvant alone into the dorsal area of each of 10 guinea pigs. After 7 days the second stage of the induction phase entailed the topical application of the undiluted test substance onto the shaved dorsal area of the test group animals using occlusive dressings for 48 hours. 14 days after the induction period, a challenge dose of the test substance 25% v/v in DIPG was selected for the challenge application to the left flank on each test animal using the same procedure as in the topical induction. The site was inspected at 24, 48 and 72 hours for the presence of erythema and oedema. Under the conditions of this study, the test material is not considered to be a contact skin sensitizer.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for skin sensitisation.
In the GPMT test the severity of effects were non-existent (erythema score < 0.5) in all organisms. The test was consistent with established adjuvant-test methodology. Under EU criteria no significant effects were observed in the in vivo GPMT study on exposure to the substance at > 1% v/v intradermal induction dose. The substance cannot be considered a skin sensitiser.
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