Registration Dossier

Administrative data

Description of key information

Substance was shown to be sensitising in the GPMT.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
May - June 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
HYPOTHESIS FOR THE ANALOGUE APPROACH
Read across is done from C14-Alkyl polyethoxy glycidylether (C14-GEE) to C12-14 Alkyl polyethoxy glycidylether (C12-14-GEE)

The production of both substances is identical: Alkyl alcohol ethoxylate (2EO) oligomers are reacted with epichlorohydrin (in slight molar excess) in the presence of a catalyst to form the corresponding epoxides. The substances are in principle UVCB because of variation in alkyl chain, number of EO (range 0 to 4, average 2) and possibility of 0 to two glycidyl (most 1) and all possible combinations.

However, the only difference between the two substances is the alkyl chain lengths distribution of the Alkyl alcohol (2EO) starting material, being either a (predominantly) 14-carbon chain length or a mixture of 12 and 14-carbon chain length in the ratio of 3:1 (C12:C14).
As consequence, these products are for 25% completely identical, whereas for the other 75% the C12-14-GEE has a slightly shorter alkyl chain compared to the C14-GEE.
For all other aspects, the substances are identical. As both have the same chemical structure they both have identical functional groups, show the same chemical reactivity and have very comparable physicochemical properties as can be seen in the comparative profiling included to the endpoint summary of chapter 7.1 on toxicokinetics. Consequently, they share the same mechanism of action. This is similarly applicable to all constituents of these UVCBs.

Related to the (small) difference in average alkyl chain-lengths between the two substances, the C12-14-GEE with on average a slightly shorter chain-length than the C14-GEE, is expected to be slightly better bioavailable (slightly smaller molecule also leading to more moles per unit of weight, slightly higher solubility, slightly lower Kow, and slightly higher vp) and is expected to have (a slightly) higher toxicity profile compared to C14-GEE.

Specifically for skin sensitisation, the molecular structure with functional groups are essential with respect to the identification of possible skin sensitizing properties. In that respect, C12-14-GEE and C14-GEE are identical. Even more, the dermal absorption of C14-GEE is expected to be slightly higher for C14-GEE (as shown by estimations from Potts & Guy derived calculations). Additionally, the dosing with C14-GEE was limited by the level of irritation, so the potential effects were not limited by insufficient level of dosing.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Already available study
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd., Burton on Trent, UK
- Age at study initiation: ca. 8-12 weeks
- Weight at study initiation: 317-430 g
- Housing: up to 2 in solid-floor polypropylene cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 4 May 1999 To: 14 June 1999
Route:
other: intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal Induction : 5% w/v in distilled water
Topical Induction : 25% v/v in distilled water
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Topical Challenge : 25% and 10% v/v in distilled water
No. of animals per dose:
10 females in test group; 5 females in control group
Details on study design:
RANGE FINDING TESTS:
intradermal induction: (4 additional animals): 1, 5, 10 and 25% w/v (5% w/v was selected)
topical induction: (2 additional animals): 25, 50, 75% v/v and undilited (25% v/v was selected)
topical challenge (2 additional animals): 5, 10, 25, and 50% v/v (10 and 25% v/v were selected)

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: single intradermal injection (with and without FCA), single epicutaneous application
- Exposure period: day 0 and day 7, respectively
- Test groups: yes
- Control group: no (vehicle only)
- Site: shoulder region
- Frequency of applications: see above
- Duration: single injection and 48-h occlusive epicutaneous application
- Concentrations: 5% w/v and 25%, respectively

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24 h (occlusive)
- Test groups: yes
- Control group: yes
- Site: flanks
- Concentrations: 25 and 10% v/v
- Evaluation (hr after challenge): 24 and 48 h after dressing removal

OTHER:
EVALUATION OF SKIN REACTIONS
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by
definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and
extending beyond area of exposure) 4



Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole
Positive control results:
2-mercaptobenzothiazole
Induction:
Intradermal: 10% in arachis oil BP
Topical: 50% in acetone:PEG 400 (70:30)
Challenge: 50% and 25% in acetone: PEG 400 (70:30)
Test: females: 10 test animals, 5 control animals
Results: 9/10 positive (90%)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25% v/v
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Other skin reactions 24 and/or 48-hour observations included small superficial scattered scabs and desquamation.
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25% v/v
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10% v/v
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Other skin reactions noted at the challenge sites of test group animals at the 24 and/or 48-hour observations included small superficial scattered scabs, desquamation and a hardened dark brown/black-coloured scab.
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10% v/v
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25% v/v
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
One animal showed erythema 1 after 24hr only.
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% v/v
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% v/v
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
One animal showed erythema 1 after 24hr only.
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10% v/v
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
other: final results
Group:
positive control
Dose level:
50% and 25% in acetone: PEG 400 (70:30)
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Summary of dermal lesions (following topical challenge) in control and test animals

Animal no.

Days after challenge application (patch removal)

Score

1

2

25% v/v

10% v/v

25% v/v

10% v/v

Control

E

O

E

O

E

O

E

O

1

1

0

1

0

0

0

0

0

-

2

0

0

0

0

0

0

0

0

-

3

0

0

0

0

0

0

0

0

-

4

0

0

0

0

0

0

0

0

-

5

0

0

0

0

0

0

0

0

-

Test 

 

 

 

 

 

 

 

 

 

1

2

2

2

2

2SsD

2

2SsD

2

+

2

2

1

2

1

2D

2

2D

2

+

3

2

1

2

1

2D

2

2D

2

+

4

2Ss

2

2Ss

2

2SsD

2

2SsD

2

+

5

2

1

2

1

2D

2

2D

2

+

6

2

1

2Ss

2

2SsD

2

2DSt

2

+

7

2

2

2

1

2Ss

2

2

2

+

8

2

2

2

1

2SsD

2

2D

2

+

9

2Ss

2

2

2

2SsD

2

2Ss

2

+

10

2Ss

2

2

1

2SsD

2

2

2

+

E= erythema, O= oedema; D= desquamation; Ss = small superficial scattered scabs

St = hardened dark brown/black-coloured scab;  + = positive effect;

Discrete or patchy erythema was noted at the challenge sites of one control group animal at the 24-hour observation at both 25% and 10% challenge. No skin reactions were noted at the challenge sites of control group animals at the 48-hour observation.

Summary of dermal lesions (following topical challenge) in control animals

 

Skin Reactions Observed After Topical Induction

Moderate and confluent to intense erythema with slight oedema was noted at the topical induction sites of all test group animals at the 1-hour observation. A hardened dark brown-coloured or light brown-coloured scab was noted at the topical induction sites of all test group animals at the 24-hour observation and precluded the evaluation of erythema and oedema at this time.

Bleeding from the intradermal induction sites was noted in six test group animals with a bleeding wound, caused by the animal scratching, also noted at the topical induction site of one of these test group animals, at the 1-hour observation.

Discrete or patchy erythema was noted at the topical induction sites of three control group animals at the 1-hour observation and four control group animals at the 24-hour observation.

Bleeding from the intradermal injection sites was noted in four control group animals at the 1-hour observation with dried blood or bleeding from the intradermal injection sites in all control group animals at the 24-hour observation.

Skin Reactions Observed After Topical Challenge

25% v/v in Distilled Water

Positive skin responses (moderate and confluent erythema with very slight to slight oedema) was noted at the challenge sites of all test group animals at the 24—hour observation. Positive skin responses (moderate and confluent erythema with slight oedema) were noted at the challenge sites of all test group animals at the 48-hour observation.

Other skin reactions noted at the challenge sites of test group animals at the 24 and/or 48-hour observations included small superficial scattered scabs and desquamation.

Discrete or patchy erythema was noted at the challenge sites of one control group animal at the 24-hour observation. No skin reactions were noted at the challenge sites of control group animals at the 48-hour observation.

10% v/v in Distilled Water

Positive skin responses (moderate and confluent erythema with very slight to slight oedema) was noted at the challenge sites of all test group animals at the 24—hour observation. Positive skin responses (moderate and confluent erythema with slight oedema) were noted at the challenge sites of all test group animals at the 48-hour observation.

Other skin reactions noted at the challenge sites of test group animals at the 24 and/or 48-hour observations included small superficial scattered scabs, desquamation and a hardened dark brown/black-coloured scab.

Discrete or patchy erythema was noted at the challenge sites of one control group animal at the 24-hour observation. No skin reactions were noted at the challenge sites of control group animals at the 48—hour observation.

Bodyweight

Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The (corrected) sensitisation rate was 100% (10/10) under the conditions of this test.
Executive summary:

A study was performed to assess the contact sensitisation potential of the test material,C12 Alkyl polyethoxy glycidylether, in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 671548lEEC). Ten test and five control animals were used for the main study. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

Intradermal Induction : 5% w/v in distilled water

Topical Induction : 25% v/v in distilled water

Topical Challenge : 25% and 10% v/v in distilled water

 

The test material produced a 100% (10/10) sensitisation rate.

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

A study was performed to assess the contact sensitisation potential of the test material, C14 Alkyl polyethoxy glycidylether, in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 671548lEEC). Ten test and five control animals were used for the main study. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:

Intradermal Induction : 5% w/v in distilled water

Topical Induction : 25% v/v in distilled water

Topical Challenge : 25% and 10% v/v in distilled water

 

The test material produced a 100% (10/10) sensitisation rate.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Substance is classified as skin sensitiser Cat.1B as it was shown to be sensitising in the GPMT with ≥ 30 % responding (i.e. 100%) at > 1 % intradermal induction dose (i.e. 5%).

As no data on respiratory sensitization is available for the substance a classification for respiratory sensitisation is not possible.