Monopentaerythritol tetraesters and dipentaerythritol hexaesters of 2-ethylhexanoic and n-valeric acids

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

14 Dec 1998-01 February 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted in 1992

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

draft

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom, UK

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.

Test material

Test material information

Constituent 1

Reference substance name:

647028-25-9

Cas Number:

647028-25-9

IUPAC Name:

647028-25-9

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, United Kingdom
- Age at study initiation: 8–12 weeks
- Weight at study initiation: 335 – 440 g
- Housing: individually or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet: Guinea Pig FD1, Special Diets Services Limited, Witham, United Kingdom; ad libitum
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 44-57
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: unchanged and arachis oil BP

Concentration / amount:

intradermal: 25%
epicutaneous: undiluted

Challenge

Route:

epicutaneous, occlusive

Vehicle:

other: unchanged and arachis oil BP

Concentration / amount:

100% and 75%

No. of animals per dose:

5 (controls), 10 (test group)

Details on study design:

RANGE FINDING TESTS (selection of concentration):
INDUCTION EXPOSURE (INTRADERMAL)
Four guinea pigs were intradermally injected with 1%, 5%, 10% and 25% w/v in arachis oil BP. The grade of erythema at the injection site was assessed approximately 24, 48 and 72 hours and 7 days after injection according to the Draize scale. The highest concentration that caused only mild to moderate skin irritation, and was well tolerated systemically, was selected for the intradermal induction phase of the main study.
INDUCTION EXPOSURE (TOPICAL)
Two guinea pigs, previously injected with Freund’s Complete Adjuvant (eighteen days earlier), were applied to the clipped flanks under occlusive dressing with undiluted test item and 75%, 50% and 25% v/v of the test item in arachis oil BP for 48 hours. The degree of erythema and oedema was assessed approximately 1, 2 and 48 hours after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.
CHALLENGE
Two guinea pigs were treated with undiluted test material and 75%, 50% and 25% v/v in arachis oil BP to the clipped flanks under occlusive conditions for an exposure period of 24 hours. Erythema and oedema score were observed approximately 1, 24, and 48 hours after dressing removal. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge phase of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 hours
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: test substance in arachis oil BP
Injection 3: test substance in a 1:1 mixture (v/v) FCA/water

Epicuteneous: test substance in arachis oil BP

- Control group:
Intradermal (3 pairs of injections)
Injection 1: a 1:1 mixture (v/v) FAC/water
Injection 2: arachis oil BP
Injection 3: arachis oil BP at 50% in a 1:1 mixture (v/v) FCA/water
Epicuteneous: arachis oil BP

- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-7
- Concentrations: intradermal 25%, epicutaneous undiluted

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: right flank (test substance undiluted) and left flank (test substance 75%)
- Concentrations: undiluted and 75%
- Evaluation (hr after challenge): 24 and 48 h after patch removal

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole (Intradermal induction concentration of 10% in arachis oil, topical induction concentration of 50% in acetone/PEG400; challenge concentration of 50 and 25% in acetone/PEG400)

Results and discussion

Positive control results:

The incidence of sensitisation in the historical positive controls was 70-100 % (based on 6 individual experiments).

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

induction: 0%; challenge: 100%

No. with + reactions:

0

Total no. in group:

5

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

induction: 0%; challenge: 100%

No. with + reactions:

0

Total no. in group:

5

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction: 25%; challenge: 75 and 100%

No. with + reactions:

0

Total no. in group:

10

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction: 25%; challenge: 75 and 100%

No. with + reactions:

0

Total no. in group:

10

Results 5

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

50%

No. with + reactions:

10

Total no. in group:

10

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.