Reaction mass of 2,4,6-tris(1-phenylethyl)phenol and bis(1-phenylethyl)phenol and o-(1-phenylethyl)phenol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March - April 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP OECD 404 guideline-compliant study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 2,4,6-tris(1-phenylethyl)phenol and 2,6-bis(1-phenylethyl) phenol

EC Number:

915-333-5

IUPAC Name:

Reaction mass of 2,4,6-tris(1-phenylethyl)phenol and 2,6-bis(1-phenylethyl) phenol

Specific details on test material used for the study:

Of note, in the absence of specific data on the registered Reaction mass of o-(1-phenylethyl) phenol and bis(1-phenylethyl) phenol and 2,4,6-tris(1-phenylethyl)phenol and the obligation to generate some data for intermediates, data from the Reaction mass of 2,4,6-tris(1-phenylethyl)phenol and 2,6-bis(1-phenylethyl) phenol have been included in the dossier by default as comparable hazard profile could be expected between both substances.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Conelli S.n.c., Via Milano 61, 28341 Arona (Novara) Italy
- Age at study initiation: 2 to 3 months
- Weight at study initiation: 2.5 to 2.8 kg
- Housing: in 62 x 47.5 x 38 cm metal cages with stainless steel feeders
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Yes (exact duration not specified)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 50 +/- 15
- Air changes (per hr): approximately 20/hour
- Photoperiod (hrs dark / hrs light): 12 / 12 (7 a.m. / 7 p.m.)


IN-LIFE DATES: From: March 4, 1997 To: March 7, 1997

Test system

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration (if solution): Not applicable


VEHICLE
Not applicable

Duration of treatment / exposure:

- 3 minutes (without patch) on one test site in one animal
- 1 hour (occlusive patch) on a second test site in the same animal
- 4 hours (occlusive patch) on a third test site in the same animal + 2 extra animals (3 total)

Observation period:

- Immediately and 72 hours after application following 3-minute and 1-hour exposures
- 1, 24, 48 and 78 hours after application following 4-hour exposure

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: approximately 6 cm²
- % coverage: Not specified
- Type of wrap if used: gauze patch loosely held in skin contact by an impermeable, non-irritant, hypoallergenic tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual substance wiped away
- Time after start of exposure: At the end of each exposure period


SCORING SYSTEM:
Skin reaction was scored using the following scale (according to Draize) :

- Erythema and eschar formation (maximum possible 4):

0 = No erythema
1 = Very slight (barely perceptible) erythema
2 = Well-defined erythema
3 = Moderate to severe erythema
4 = Severe erythema (beef redness) to slight eschar formation (injuries in depth)

- Edema formation (maximum possible 4):

0 = No edema
1 = Very slight (barely perceptible) edema
2 = Slight edema (area edges well defined by definite raising)
3 = Moderate edema (raised approximately 1 mm)
4 = Severe edema (raised more than 1 mm and extending beyond exposure area)

Dermal irritation was evaluated in conjunction with the nature and reversibility or otherwise of the responses observed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

See table below

Other effects:

No other effect observed

Any other information on results incl. tables

Animal number		1			2	3
Exposure duration		3 min	1 h	4 h	4 h	4 h
Erythema score at	3 min	0	NP	NP	NP	NP
	1 h	NP	0	0	1	0
	24 h	NP	NP	0	0	0
	48 h	NP	NP	0	0	0
	72 h	0	0	0	0	0
Edema score at	3 min	0	NP	NP	NP	NP
	1 h	NP	0	0	0	0
	24 h	NP	NP	0	0	0
	48 h	NP	NP	0	0	0
	72 h	0	0	0	0	0

NP: Not Performed

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The very slight erythema observed in 1 out of 3 rabbits one hour after a 4-hour occlusive patch application of the test substance was isolated, reversible and was therefore considered incidental. As no other local change was observed, the test item was considered as non irritant and therefore not classified for skin irritation according to the criteria of Annex VI Directive 67/748/EEC or UN/EU GHS.

Executive summary:

In a primary dermal irritation study (RBM study No. 970073), three male New Zealand White rabbits (2- to 3-month old), were dermally exposed to 0.5 mL of Tristyrenated phenol/Distyrenated phenol (75/25 molar %) applied as such for 3 minutes (one rabbit), 1 hour (same rabbit) or 4 hours (all 3 rabbits) to a clipped skin surface area of approximately 6 cm² on the trunk of the animals. Test sites were covered with an occlusive dressing for the duration of exposure. Local changes at application sites were then observed immediately and 72 h after the 3-min and 1-h exposures, and 1, 24, 48 and 72 h after the 4-h exposure. Local irritation was evaluated by scoring erythema/eschar and edema formation for each rabbit, according to Draize's method.

 

A very slight erythema (grade 1) was observed in one out of 3 rabbits one hour after the 4-hour occlusive patch application. As this finding was isolated and reversible, it was considered incidental. As no other local change was observed, the test item was considered as non irritant to the skin.

 

In this study, Tristyrenated phenol/Distyrenated phenol (75/25 molar %) is not a dermal irritant based on the absence of relevant local changes following occlusive patch application for up to 4 hours.

TSP/DSP is not classified for skin irritation according to the criteria of Annex VI Directive 67/748/EECor UN/EU GHS.