Alcohols C13-15 (branched and linear, odd numbered), reaction product with 1-chloro-2,3-epoxypropane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1990-08-14 to 1990-11-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted in compliance with GLP principle and Guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study had been conducted in 1990, before development of the LLNA method

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C13-15 (odd numbered, branched and linear)

Molecular formula:

C13H28O and C15H32O

IUPAC Name:

Alcohols, C13-15 (odd numbered, branched and linear)

Constituent 2

Reference substance name:

Alcohols, C13, branched glycidyl ethers

Molecular formula:

C16H32O2

IUPAC Name:

Alcohols, C13, branched glycidyl ethers

Constituent 3

Reference substance name:

[(tridecyloxy)methyl]oxirane

EC Number:

276-765-1

EC Name:

[(tridecyloxy)methyl]oxirane

Cas Number:

72689-40-8

Molecular formula:

C16H32O2

IUPAC Name:

2-[(tridecyloxy)methyl]oxirane

Constituent 4

Reference substance name:

Alcohols, C15, branched glycidyl ethers

Molecular formula:

C18H36O2

IUPAC Name:

Alcohols, C15, branched glycidyl ethers

Constituent 5

Reference substance name:

[(pentadecyloxy)methyl]oxirane

EC Number:

302-058-5

EC Name:

[(pentadecyloxy)methyl]oxirane

Cas Number:

94088-56-9

Molecular formula:

C18H36O2

IUPAC Name:

2-[(pentadecyloxy)methyl]oxirane

Constituent 6

Reference substance name:

secondary reaction products of Oxirane, mono{[C13-15 (odd numbered, linear and branched)-alkyloxy)methyl] derivs.

Molecular formula:

UVCB, not applicable

IUPAC Name:

secondary reaction products of Oxirane, mono{[C13-15 (odd numbered, linear and branched)-alkyloxy)methyl] derivs.

Constituent 7

Reference substance name:

unknown constituents

IUPAC Name:

unknown constituents

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material: ALKYL (C13-C15) - GLYCIDYLETHER
- Physical state: Liquid
- Lot/batch No.: DC 1295.3
- Storage condition of test material: At room temperature, in the dark.

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Albino

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: BRL Bio1ogica1 Research Laboratories Ltd. Wölferstrasse 4 CH - 4414 Füllinsdorf
- Age at study initiation: males (7 weeks); females (8 weeks).
- Weight at study initiation: males (332 - 358 g); females (323 - 342 g)
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding.
- Diet: Pelleted standard Kliba 342 ad libitum
- Water: Community tap water from Itingin ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3 °C
- Humidity (%): 40 - 70%
- Air changes (per hr): Air-conditioned with 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light/12 hours dark

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: Oleum arachidis

Induction 2

Concentration / amount:

Intradermal injections: 5% with oleum arachidis
Epidermal applications: 75% in vaseline
Challenge: 25% in vaseline

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: Oleum arachidis

Challenge 2

Concentration / amount:

Intradermal injections: 5% with oleum arachidis
Epidermal applications: 75% in vaseline
Challenge: 25% in vaseline

No. of animals per dose:

Control group: 5 males and 5 females
Test group: 10 males and 10 females

Details on study design:

RANGE FINDING TESTS:
Intradermal injections: Intradermal injections (0.1 ml/site) were made into the clipped flank of two guinea-pigs at concentrations of 5, 3 and 1% of the test article in oleum arachidis. The resulting dermal reactions were assessed 24 hours later.
Epidermal applications: Patches of filter paper (2 x 2 cm) were saturated with the undiluted test article and with concentrations of 75%, 50% and 25% of the test article in vaseline 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 trunk and covered with impervious adhesive tape. The dressings were removed after an exposure period of 24 hours and the reaction sites were assessed.
MAIN STUDY:
Induction
Intradermal injections: An area of dorsal skin from the scapular region (approximately 6 x 8 cm) was clipped from the hair. Three pairs of intradermal injections ( 0.1 ml/site) were made at the border of a 4 x 6 cm area in the clipped region as follows:
Test group:
1) Freund’s complete adjuvant 50:50 with physiological saline.
2) The test article, dilute to 5% with oleum arachidis.
3) The test article at the concentration used in (2), emulsified in a 50:50 mixture of Freund’s complete adjuvant and the vehicle used in (2).
Control group:
1) Freund’s complete adjuvant 50:50 with physiological saline.
2) Vehicle used in (2) for test group.
3) Freund’s complete adjuvant 50:50 with physiological saline.
Epidermal applications: One week after the injections, the scapular area (approximately 6 × 8 cm) was again clipped and shaved free of hair. A 2 × 4 cm patch of filter paper was saturated with the test article (75% in vaseline) and placed over the injection sites of the test animals. The patch was covered by aluminum foil and firmly secured by an elastic plaster wrapped around the trunk of the animal and secured with impervious adhesive tape. The dressings were left in place for approximately 48 hours.
The guinea-pigs of the control group were treated as described above with the omission of test article.
Reaction sites were assessed for erythema and edema 24 and 48 hours after removal of the dressing.
Challenge:
The test and control guinea-pigs were challenged two weeks after the epidermal induction application.
Hair was clipped and shaved from a 5 × 5 cm area on the left and right flank of each guinea-pig. Two patches (2 × 2 cm) of filter paper were saturated with a) non-irritant concentration (25% in Vaseline) of the test article and b) with the vehicle only and applied to the (a) left flank and (b) right flank using the same method as for the epidermal application.
The dressings were removed approximately 24 hours later. The sites were assessed for erythema and edema 24 and 48 hours after removal of the dressing.
The control guinea-pigs were treated in the same way as described as above.
Re-challenge:
A second challenge was performed two weeks after the first challenge. The treatment procedure for the animals of the test group was similar as described for the first challenge with the exception that the flanks of the guinea-pigs and the vehicle used for the test article dilution were changed (a – vehicle; b- 25% test article in oleum arachides).
The control animals were treated with the vehicle alone on the left flank.

Positive control substance(s):

yes

Remarks:

Formaldehydloesung (HCHO)

Results and discussion

Positive control results:

HCHO possess an strong skin sensitizing potential in the guinea pig.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.1 ml/site

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.1 ml/site. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.1 ml/site

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.1 ml/site. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25% in vaseline

No. with + reactions:

20

Total no. in group:

20

Clinical observations:

slight to moderate erythema/Edema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% in vaseline. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: slight to moderate erythema/Edema.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25% in vaseline

No. with + reactions:

20

Total no. in group:

20

Clinical observations:

slight to moderate erythema/Edema

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% in vaseline. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: slight to moderate erythema/Edema.

Results 5

Reading:

rechallenge

Hours after challenge:

24

Group:

negative control

Dose level:

0.1ml/site

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.1ml/site. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 6

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

25% in oleum arachides

No. with + reactions:

17

Total no. in group:

20

Clinical observations:

slight to moderate erythema/Edema

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 25% in oleum arachides. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: slight to moderate erythema/Edema.

Results 7

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

25% in oleum arachides

No. with + reactions:

11

Total no. in group:

20

Clinical observations:

slight to moderate erythema/Edema

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 25% in oleum arachides. No with. + reactions: 11.0. Total no. in groups: 20.0. Clinical observations: slight to moderate erythema/Edema.

Results 8

Reading:

rechallenge

Hours after challenge:

24

Group:

positive control

Dose level:

20% HCHO in water

No. with + reactions:

7

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Remarks:

Subproject 270066, Appendix E in test report

Any other information on results incl. tables

Sensitizing effects Positive erythema reactions after the first challenge procedure   after 24 hours after 48 hours   Positive / total ———————— % positive of total Positive / total ———————— % positive of total Control group     ALKYL (C13-C15)- GLYCIOYLETHER (left flank) 0 / 10 ——— 0 0 / 10 ——— 0 vehicle only (right flank) 0 / 10 ——— 0 0 / 10 ——— 0 Test group     ALKYL (C13-C15)- GLYCIOYLETHER (left flank) 20 / 20 ———— 100 20 / 20 ———— 100 vehicle only (right flank) 0 / 20 ———— 0 0 / 20 ———— 0 Positive erythema reactions after the second challenge procedure   after 24 hours after 48 hours   Positive / total ———————— % positive of total Positive / total ———————— % positive of total Control group vehicle only (left flank) 0 / 10 ——— 0 0 / 10 ——— 0 Test group ALKYL (C13-C15)- GLYCIOYLETHER (right flank) 17 / 20 ———— 85 11 / 20 ———— 55 vehicle only (left flank) 0 / 20 ———— 0 0 / 20 ———— 0 Mortality / Viability No death occurred during the study. Symptoms, systemic No systemic symptoms were observed in the animals. Body weights The body weight gain of the animals was not affected adversely during the study.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

This study was conducted according to Maximization test and the result indicated that test substance may cause skin sensitization to guinea pigs.

Executive summary:

This study was conducted to evaluate the potential of the test article to induce hypersensitivity in guinea pigs using the Maximization test.

For the intradermal induction phase of the study, three pairs of intradermal injections were made at the scapular skin of test group and control group as above mentioned method in which the test article was diluted to 5% with oleum arachidis. One week later, the epidermal induction started. Scapular skin was clipped and shaved free of hair. A patch was saturated with 75% the test article in vaseline and placed over the injection sites of test group and only vaseline was placed on the skin of control group.

The test and control group were challenged two weeks after the epidermal induction application. Two patches were saturated with a) 25% in vaseline of the test article and b) with the vehicle only and applied to the left flank and right flank using the same method as for the epidermal application.

A second challenge was performed two weeks after the first challenge. The treatment procedure was similar as described for the first challenge with the exception that vehicle was applied to the left flank and 25% test article in oleum arachides was applied to the right flank.

The challenge site was evaluated 24 and 48 hours after removal of the patch. The reactions were scored on the basis of the Draize score.

The test result of the first challenge in test group showed positive erythema reactions at 24h and 48h when treated with 25% test article in vaseline. The test result of the second challenge in test group showed positive erythema reactions at 24h and 48h when treated with 25% test article dilution in oleum arachides.

Based on the study results, it is concluded that test substance can be classified as skin sensitizer (category 1) in accordance with CLP (Regulation EC No. 1272/2008).