esterification product of 2-hydroxypropane-1,3-diyl-bis(2-methylprop-2-enoate) and 3-hydroxypropane-1,2-diyl-bis(2-methylprop-2-enoate) and diphosphorus pentoxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September-October 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: OECD Guidelines for Testing of Chemicals, Number 406 "Skin Sensitization", adopted by the Council on July 17, 1992 (reported Paris, April 29, 1993).

Deviations:

yes

Remarks:

Stability of test item in 1:1 (v/v) mixture of FCA/physiol saline is unknown. Formulation trials were not inspected by quality assurance unit.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Directive 96/54/EEC, B.6 "Acute Toxicity- Skin Sensitization", July 30, 1996.

Deviations:

yes

Remarks:

Stability of test item in 1:1 (v/v) mixture of FCA/physiol saline is unknown. Formulation trials were not inspected by quality assurance unit.

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

Glypho

IUPAC Name:

Glypho

Details on test material:

- Name of test material (as cited in study report:Glypho
- Substance type:Yellowish liquid
- Physical state:Liquid
- Lot/batch no.:AH2/170
- Expiration date of the lot/batch: 01-Feb-2002
- Stability under test conditions:Stable in polyethylene glycol for at least 48 hours at room temperature.
- Storage condition of test material: In the original container, in the refrigerator (range of 5 +/- 3 degrees C), away from direct sunlight.

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Ibm: GOHHI; SPF-quality guinea pigs (synonym: Himalayan spotted)

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation:4-6 weeks
- Weight at study initiation:391-410 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418, batch no. 91/01, guinea pig breeding/maintenance diet containing Vitamin C, ad libitum
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, ad libitum
- Acclimation period:1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 +/- 3 degrees C
- Humidity (%):30-70%
- Air changes (per hr):10-15
- Photoperiod (hrs dark / hrs light):12/12
IN-LIFE DATES: From:12 Sept 2001 To: 22 Oct 2001

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Induction 2

Concentration / amount:

50% dilution of the test article in PEG 300 and in an emulsion of Freund's Complete Adjuvant (FCA)/physiological saline for the induction exposure. 25% dilution fo the test article in PEG 300 was used in the challenge exposure.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Challenge 2

Concentration / amount:

50% dilution of the test article in PEG 300 and in an emulsion of Freund's Complete Adjuvant (FCA)/physiological saline for the induction exposure. 25% dilution fo the test article in PEG 300 was used in the challenge exposure.

No. of animals per dose:

10 males/treatment, 5 males/control

Details on study design:

- Duration of observation period following administration:At times specified during pretest, induction, and challenge periods
- Frequency of observations and weighing: Viability/Mortality: Daily from delivery to termination. Clinical signs: Daily from delivery to termination. Skin reactions: 24 and 48 hours after test article administration. Body Weights: At pretest and acclimation start, day 1 and termination of the test.
- Necropsy of survivors performed: no

Challenge controls:

Administered PEG 300 only

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole

Results and discussion

Positive control results:

10/10, 100% response

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25% test article in PEG 300

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No toxic sympotoms were evident in the guinea pigs of the control or test groups.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% test article in PEG 300. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No toxic sympotoms were evident in the guinea pigs of the control or test groups..

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Based on the results this study, there was no evidence of skin sensitization following treatment with the test article.

Executive summary:

The dermal sensitization potential of the test article (liquid, purity >98%, batch no. AH2/170) was evaluated in the Maximization Test using male Himalayan spotted guinea pigs. This study was performed in accordance with Swiss GLP (2000) and OECD GLP (1997). The study design was based on OECD 406 (1993) and Directive 96/54/EEC, B.6 (1996). The test article was prepared in PEG 300 (vehicle) just prior to each dosing procedure. A pre-test rangefinder determined the appropriate doses for the intradermal and epidermal inductions and challenge phase. The test group (10 animals) received intradermal induction injections of 0.1 ml/site of a 1:1 mixture of Freund’s Complete Adjuvant (FCA):saline, 50% test article in vehicle, and 50% test article in 1:1 FCA/saline. A control group (5 animals) received the same induction treatment with the exclusion of test article. Pre-test results: The epidermal induction of sensitization was conducted under occlusion with 75% MTDID 16591 in vehicle (test group) or vehicle only (control group) one week after the intradermal induction. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of 25% of the test article and vehicle only under occlusive dressing. Skin reactions were evaluated at 24 and 48 hours after removal of the dressing. A positive control (2-mercaptobenzothiazole) is tested by this contract lab approximately every 6 months and the most recent test confirmed the validity of the experimental technique. There was no evidence of skin sensitization following treatment with the test article. No erythema or edema was observed at any site in either the control or test article group (0/10). A loss of body weight (7.4%) was observed in 1 test group animal during the acclimatization period; the animal recovered between the treatment start and the end of the study. Based on the results this study, there was no evidence of skin sensitization following treatment with the test article.