Registration Dossier

Administrative data

Description of key information

An analogue test item (EC 265-205-1) was determined to be non-sensitising (EPA OPPTS 870.2600 and OECD 406).

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:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
(the environmental conditions deviated from the guideline as the ranges used were larger)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Testing for other compliance purposes outside EU
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hilltop Lab Animals, Inc., Scottdale, PA
- Animal husbandry was based on the standards recommended by the Guide for the Care and Use of Laboratory Animals
- Age at study initiation: 6 weeks (males); 8 weeks (females)
- Weight at study initiation: 366-439 g (males); 319-380 g (females)
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): PMI Certified Guinea Pig Chow #5026 (Purina Mills, Inc.), ad libitum
- Water (e.g. ad libitum): municipal tap water treated by reverse osmosis, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 60-77 ºF (16-25 ºC)
- Humidity (%): 23-49 %
- Air changes (per hr): 10-15 air charges per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: 05/12/2000 To: 11/01/2001
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction exposure: 50% or 40 % w/v in the vehicle
1st Challenge and challenge control: 25% w/v in the vehicle
2nd Challenge: 20 and 10% w/v in the vehicle
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction exposure: 50% or 40 % w/v in the vehicle
1st Challenge and challenge control: 25% w/v in the vehicle
2nd Challenge: 20 and 10% w/v in the vehicle
No. of animals per dose:
- Twenty animals were used in the test group, 10 males and 10 females
- Ten animals were used for the positive control, 5 males and 5 females
- Ten animals were used for the challenge control group, 5 males and 5 females
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three, on days 1, 7 and 14
- Exposure period: 6 hours, after which the site was wiped down with gauze moistened in deionised water to remove any residue
- Site: left dorsal side of the animal, called site 1
- Test groups: 50% in the first induction then 40% for the second and third induction exposures, which were all applied at site 1
- Control group: animals were exposed three times to 0.1% concentration of the test material in the same manner as the test group
- Frequency of applications: every seven days until all three consecutive applications have been administered

B. CHALLENGE EXPOSURE
- Rest time before challenge: approximately 2 weeks
- No. of exposures: two, the Challenge and the Rechallenge
- Exposure period: 6 hours, after which the site was wiped down with gauze moistened in deionised water to remove any residue
- Day(s) of challenge: application on Day 28 and Day 35 for the challenge and rechallenge respectively
- Site: three sites were used, for exposure, on the right dorsal side of the animal, called site 2, 4 and 6
- Test groups: 25% w/v of the test material was applied to site 2 in the challenge, then 20% and 10% w/v was applied at sites 4 and 6 during the rechallenge
- Challenge control group: the challenge control was performed concurrently with the test and applied in the same manner as the test material
- Positive Control group: the DNCB control and DNCB challenge were performed on Day 28 only, at site 2 and 4. 0.1% was applied at site 2 and 0.05% was applied at site 4
- Wrapping: following application of the test material, challenge control or positive control the trunk of the animal was wrapped in an occlusive manner

C. OBSERVATIONS
-Dermal reactions were recorded at 24 and 48 hours following application of the test material during induction exposure and both the challenge and rechallenge
-Clinical observations and mortality were recorded twice daily
-Body weights were recorded on the day before dosing in the induction, challenge and rechallenge
- All animals were euthanized after the final scoring
Positive control substance(s):
yes
Remarks:
DNCB (1-chloro-2,4-dinitrobenzene) in acetone/ethanol: 0.1% w/v for the induction exposure and then 0.1% and 0.05% w/v in the challenge exposure
Reading:
other: challenge
Hours after challenge:
24
Group:
test group
Dose level:
25 % w/v
No. with + reactions:
6
Total no. in group:
20
Reading:
other: challenge
Hours after challenge:
48
Group:
test group
Dose level:
25 % w/v
No. with + reactions:
9
Total no. in group:
20
Reading:
other: challenge control
Hours after challenge:
24
Group:
other: challenge control
Dose level:
25 % w/v
No. with + reactions:
2
Total no. in group:
10
Reading:
other: challenge control
Hours after challenge:
48
Group:
other: challenge control
Dose level:
25 % w/v
No. with + reactions:
1
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
20% w/v
No. with + reactions:
0
Total no. in group:
20
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
20% w/v
No. with + reactions:
0
Total no. in group:
20
Reading:
rechallenge
Hours after challenge:
24
Group:
other: rechallenge control
Dose level:
20 % w/v
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
48
Group:
other: rechallenge control
Dose level:
20% w/v
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
10% w/v
No. with + reactions:
2
Total no. in group:
20
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
10% w/v
No. with + reactions:
1
Total no. in group:
20
Reading:
rechallenge
Hours after challenge:
24
Group:
other: rechallenge control
Dose level:
10% w/v
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
48
Group:
other: rechallenge control
Dose level:
10% w/v
No. with + reactions:
0
Total no. in group:
10
Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test there is no significant difference in the dermal response after the challenge or rechallenge applications of the test material. The test material was determined to be not sensitising and therefore does not require classification according to Regulation (EC) 1272/2008.
Executive summary:

In a GLP compliant Buehler test, the skin sensitisation potential was assessed according to standardised guidelines OECD 406 and EPA OPPTS 870.2600. Twenty Guinea pigs were exposed to the test material first using three induction exposures at 50 and 40 % w/v, then in a challenge and rechallenge exposure at 25, 20 and 10 % w/v. None of the test animals displayed a dermal reaction greater than the challenge control during the challenge or rechallenge. Under the conditions of the test, the test material was determined to be not sensitising and therefore does not require classification according to Regulation (EC) 1272/2008.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See read-across justification attached in Section 13.
Reason / purpose:
read-across source
Reading:
other: challenge
Hours after challenge:
24
Group:
test group
Dose level:
25 % w/v
No. with + reactions:
6
Total no. in group:
20
Reading:
other: challenge
Hours after challenge:
48
Group:
test group
Dose level:
25% w/v
No. with + reactions:
9
Total no. in group:
20
Reading:
other: challenge control
Hours after challenge:
24
Group:
other: challenge control
Dose level:
25% w/v
No. with + reactions:
2
Total no. in group:
10
Reading:
other: challenge control
Hours after challenge:
48
Group:
other: challenge control
Dose level:
25% w/v
No. with + reactions:
1
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
20% w/v
No. with + reactions:
0
Total no. in group:
20
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
20% w/v
No. with + reactions:
0
Total no. in group:
20
Reading:
other: rechallenge control
Hours after challenge:
24
Group:
other: rechallenge control
Dose level:
20% w/v
No. with + reactions:
0
Total no. in group:
10
Reading:
other: rechallenge control
Hours after challenge:
48
Group:
other: rechallenge control
Dose level:
20% w/v
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
10% w/v
No. with + reactions:
2
Total no. in group:
20
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
10% w/v
No. with + reactions:
1
Total no. in group:
20
Reading:
other: rechallenge control
Hours after challenge:
24
Group:
other: rechallenge control
Dose level:
10% w/v
No. with + reactions:
0
Total no. in group:
10
Reading:
other: rechallenge control
Hours after challenge:
48
Group:
other: rechallenge control
Dose level:
10% w/v
No. with + reactions:
0
Total no. in group:
10
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a GLP compliant Buehler test, the skin sensitisation potential of an analogue substance (EC 265-205-1) was assessed according to standardised guidelines OECD 406 and EPA OPPTS 870.2600. Twenty Guinea pigs were exposed, first using three induction exposures at 50 and 40 % w/v, then in a challenge and rechallenge exposure at 25, 20 and 10 % w/v. None of the test animals displayed a dermal reaction greater than the challenge control during the challenge or rechallenge. Under the conditions of the test, the test material was determined to be not sensitising and therefore does not require classification according to Regulation (EC) 1272/2008.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on results from a modified Buehler assay involving an analogue substance (EC 265-205-1), the criterion for skin sensitisation was not met (≤ 15% of the test animals responded to rechallenge when topical induction dose was > 20 %). In accordance with ECHA Guidance on the Application of the CLP Criteria (Version 4.1; June 2015), classification as a skin sensitiser is not required under the terms of Regulation (EC) No 1272/2008.