reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

between 12 January 2000 and 19 January 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): OS 144267
- Molecular formula (if other than submission substance): C21H34O3
- Molecular weight (if other than submission substance): 334.491
- Smiles notation (if other than submission substance): Oc1c(C(C)(C)C)cc(cc1C(C)(C)C)CCC(=O)OCCCC
- InChl (if other than submission substance): 1S/C21H34O3/c1-8-9-12-24-18(22)11-10-15-13-16(20(2,3)4)19(23)17(14-15)21(5,6)7/h13-14,23H,8-12H2,1-7H3
- Structural formula attached as image file (if other than submission substance): see Fig.1
- Substance type: alkylated phenol
- Physical state: yellow crystalline solid block
- Analytical purity: Data relating to the identity, purity and stability of the test material are the
responsibility of the Sponsor.
- Storage condition of test material: room temperature in the dark
- Other: For the purpose of this study the test material was warmed in a water bath set at 60°C to produce a liquid. The test material was allowed to cool to room temperature before use.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.80 to 2.87 kg
- Housing: individually in suspended metal cages.
- Diet (e.g. ad libitum): ad libitum (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: From: To:

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: fur was clipped from the dorsal/flank area using veterinary clippers.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): neat substance

Duration of treatment / exposure:

4 h

Observation period:

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale of Draize (1977).
An additional observation was made on Day 7 to assess the reversibility of skin reactions.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: not reported
- % coverage: not reported
- Type of wrap if used: an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no. The residual test material was removed by gentle swabbing with cotton wool soaked in 74% industrial Methylated Spirits.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
The test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H, (1977) "Dermal
and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington
DC p.31:
EVALUATION OF SKIN REACTIONS:
Erythema and Eschar Formation:
0 - No erythema
1 - Very slight erythema (barely perceptible)
2 - Well-defined erythema
3 - Moderate to severe erythema
4 - Severe erythema (beet redness) to slight eschar formation (injuries in depth)

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: overall at 24, 48 and 72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: max.score at 24 and 48 h

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: overall at 24, 48 and 72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: max. score at 24 and 48 h

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: overall at 24, 48 and 72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: max. score at 24 and 48 h

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

0

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: overall at 24, 48 and 72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: max.score at 24 and 48 h

Irritant / corrosive response data:

Very slight erythema was noted at all treated skin sites at the 1-hour observation with very slight to well defined erythema at the 24 and 48-hour observations. Very slight erythema was noted at one treated skin site at the 72-hour observation.
Very slight oedema was noted at one treated skin site at the 24 and 48-hour observations.
Loss of skin elasticity was noted at two treated skin sites at the 48-hour observation.
All treated skin sites appeared normal at the 7-day observation.

Other effects:

No

Any other information on results incl. tables

Table 1. The individual scores for erythema/eschar and oedema

INDIVIDUAL SKIN REACTIONS
Skin Reaction	Observation Time	Individual Scores - Rabbit Number and Sex (Bodyweight kg)			Total
		134 Male (2.87)	135 Male (2.80)	137 Male (2.81)
Erythema/Eschar Formation	1 Hour	1	1	1	( 3 )
	24 Hours	1	1	2	4
	48 Hours	1	1 Le	2 Le	( 4 )
	72 Hours	0	0	1	1
	7 Days	0	0	0	0
Oedema Formation	1 Hour	0	0	0	( 0 )
	24 Hours	0	0	1	1
	48 Hours	0	0	1	( 1 )
	72 Hours	0	0	0	0
	7 Days	0	0	0	(0)
Sum of 24 and 72-hour Readings (S): 6
Primary Irritation Index (S/6): 6/6 = 1.0
Classification: MILD IRRITANT
(    ) = Total values not used for calculation of primary irritation index Le = loss of skin elasticity

Table 2. Mean values required for EU labelling regulations

INDIVIDUAL DAILY AND MEAN SCORES FOR DERMAL IRRITATION FOLLOWING 4-HOUR EXPOSURE REQUIRED FOR EU LABELLING REGULATIONS
Skin Reaction	Reading (Hours)	Individual Scores - Rabbit Number and Sex (Bodyweight kg)
		134 Male (2.87)	135 Male (2.80)	137 Male (2.81)
Erythema/Eschar Formation	24	1	1	2
	48	1	1	2
	72	0	0	1
Total		2	2	5
Mean Score		0.7	0.7	1.7
Oedema Formation	24	0	0	1
	48	0	0	1
	72	0	0	0
Total		0	0	2
Mean Score		0.0	0.0	0.7

Applicant's summary and conclusion

Interpretation of results:

other: not classified as irritant or corrosive according to the EU Directive 67/548/EEC.

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The test material, OS 144267, produced a primary irritation index of 1.0 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive
according to EU labelling regulations. No symbol and risk phrase are required.

Executive summary:

A GLP study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight oedema. Loss of skin elasticity was noted at two treated skin sites. All treated skin sites appeared normal at the 7-day observation. The test material produced a primary irritation index of 1.0 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations (EU Directive 67/548/EEC). No symbol and risk phrase are required.