Reaction Mass of 4-tert-butyl-2-hydroxycyclohexyl methacrylate and 5-tert-butyl-2-hydroxycyclohexyl methacrylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 September 1998 - 04 March 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

other: Waxy solid

Details on test material:

Test material name: TBE

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three male young adult New Zealand White rabbits were used. They were within the weight range 2.55-2.70 kg on arrival, and were supplied by Harlan UK, Shaw's Farm, Blackthorn, Bicester, OX6 0TP. They arrived at Elphinstone Research Centre (Inveresk) on 18 August 1998.Animals were acclimatised for at least 7 days prior to commencement of the study.Animals were housed individually in stainless stell cages (77 x 70 x 50 cm) with a Noryl moulded dual lever interior and perforated floor beneath which was an absorbent paper lined tray. Each cage was supplied with an automatic watering valve and a food hopper. Water (mains supply) and Tekland Diet food were supplied ad libitum throughout the study. Cabbage and hay were offered as a supplement to each animalca. twice weekly. Food and water were analysed and were not considered to contain any additional substances in sufficient concentration to have any influence on the outcome of the study.Mean environmental temperatures ranged from minimum and maximum values of 19-20 °C. Mean relative humidity was 47 %. A 12 h light/dark cycle was utilised (light hours 0700-1900) with a minimum of 15 air changes per hour.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 g TBE was applied topically to each animal to the wetted dorsal trunk and covered with a water moistened gauze patches (2.5 cm x 2.5 cm), semi-occlusive tape and elastic bandage.

Duration of treatment / exposure:

After a contact period of 4 h, the patch was removed and remaining test item washed from the contact area using distilled water. The test sites were delineated.

Observation period:

Test sites were examined 1, 24, 48 and 72 h after patch removal. Observations continued up to Day 18 to fully evaluate the reversibility of the reactions, however, as the reactions were deemed irreversible the study was concluded.

Number of animals:

3

Details on study design:

0.5 g TBE was applied topically to each animal to the wetted dorsal trunk and covered with a water moistened gauze patches (2.5 cm x 2.5 cm), semi-occlusive tape and elastic bandage.After a contact period of 4 h, the patch was removed and remaining test item washed from the contact area using distilled water. The test sites were delineated.Test sites were examined 1, 24, 48 and 72 h after patch removal. Skin reactions were graded according to the scoring system detailed in Table 1 and Table 2.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

2.3

Max. score:

3

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

2.7

Max. score:

3

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

2.3

Max. score:

3

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

7 d

Score:

1.3

Max. score:

2

Results 5

Irritation parameter:

erythema score

Basis:

mean

Time point:

14 d

Score:

0.3

Max. score:

1

Irritant / corrosive response data:

Erythema and oedema skin reaction scores are presented in Table 3 and Table 4, respectively.No oedema was noted in any animal during the observation period.Very slight Erythema was noted in 2 animals and well defined in the third animal 1 h after patch removal. Well defined erythema was noted from 24 h after patch removal up to Day 6 in all animals. Very slight to well defined erythema was noted from Day 7 up to Day 14 in all aniamls.

Other effects:

Additional observations (dry and flaky skin) was noted from Day 6 to 18 in two animals and from Day 7 to 18 in the third animal.

Any other information on results incl. tables

Table 3       Erythema Reaction Scores and Body Weight

Animal	Body Weight at Dosing (kg)	Time After Patch Removal (or Day of Study) Reaction Scores
		1 h	24 h	48 h	72 h	Day 5	Day 6*	Day 7	Day 9	Day 11	Day 14	Day 15
1	3.35	2	3	3	2	2	2	1	1	0	0	-
2	3.07	1	2	3	3	3	2	2	1	1	0	-
3	3.23	1	2	2	2	2	2	2	1	1	1	0

* animal shaved

- animal not observed

see Table 1 for scoring system

Table 4       Oedema Reaction Scores

Animal	Time After Patch Removal (or Day of Study) Reaction Scores
	1 h	24 h	48 h	72 h	Day 5	Day 6*	Day 7	Day 9	Day 11	Day 14	Day 15
1	0	0	0	0	0	0	0	0	0	0	-
2	0	0	0	0	0	0	0	0	0	0	-
3	0	0	0	0	0	0	0	0	0	0	0

* animal shaved

- animal not observed\

see Table 2 for scoring system

Table 5       Additional Observations

Animal	Observation	Day of Study
1	Dry flaky skin evident at test sight	7, 9, 11, 14, 15, 18
2	Dry flaky skin evident at test sight	6, 7, 9, 11, 14, 15, 18
3	Dry flaky skin evident at test sight	6, 7, 9, 11, 14, 15, 18

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Under the conditions of the study , TBE is considered to be irritating to rabbit skin.

Executive summary:

The acute dermal irritation of TBE was investigated in New Zealand White rabbits.

One group of 3 male rabbits was subjected to a 4 h exposure of 0.5 g of TBE, as supplied, on to the wetted dorsal trunk under a water moistened semi-occlusive patch. The test sites were examined for evidence of irritation 1, 24, 48 and 72 h after patch removal. Observations were continued up to Day 18 to fully evaluate the reversibility of the reactions.

No oedema was noted in any animal during the observation period.

Very slight Erythema was noted in 2 animals and well defined in the third animal 1 h after patch removal. Well defined erythema was noted from 24 h after patch removal up to Day 6 in all animals. Very slight to well defined erythema was noted from Day 7 up to Day 14 in all aniamls.

Dry flaky skin was noted at the test site from Days 6 or 7.

Under the conditions of the study, TBE is considered to be irritating to rabbit skin.