Condensation products of oil shale alkylresorcinols and formaldehyde

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 March 2004 and 13 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

447-830-3

EC Name:

-

Molecular formula:

Not applicable to this UVCB substance.

IUPAC Name:

2-ethylphenol; 3,5-dimethylphenol; formaldehyde; phenol

Test material form:

other: solid resin

Details on test material:

Date received: 30 January 2004
Storage conditions: room temperature in the dark under nitrogen

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: 12 - 20 weeks old
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): free access to certified rabbit diet
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: at least five days
- Other: The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

IN-LIFE DATES: From: 30 March 2004 To: 13 April 2004

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Distilled

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

Observations made at 1 hour, 24 hours, 48 hours, 72 hours and 7 days after removal of the patch.

Number of animals:

3

Details on study design:

TEST MATERIAL APPLICATION
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 g of the test material, moistened with 0.5 mL of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset and the animal was returned to its cage for the duration of the exposure period.
After consideration of the skin reactions produced in the first animal, two additional animals were treated with 0.5 g of test material moistened with 0.5 mL of distilled water. One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application.

SCORING SYSTEM: Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.47:

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean of time points 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean of time points 24, 48 and 72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 3 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean of time points 24, 48 and 72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean of time points 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean of time points 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean of time points 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritant / corrosive response data:

4 hour exposure:
Very slight erythema was noted at two treated skin sites one hour after patch removal. Very slight to well-defined erythema was noted at all treated skin sites at the 24 and 48-hour observations with very slight erythema at two treated skin sites at the 72-hour observation.
Very slight oedema was noted at one treated skin site one hour after patch removal with very slight to slight oedema at two treated skin sites at the 24-hour observation and very slight oedema at one treated skin site at the 48-hour observation.
One treated skin site appeared normal at the 72-hour observation and the remaining two treated skin sites appeared normal at the 7-day observation.

1 hour exposure:
Very slight erythema was noted at the treated skin site at the 24 and 48-hour observations.
The treated skin site appeared normal at the 72-hour observation.

3 minutes exposure:
No evidence of skin irritation was noted during the study.

Other effects:

None

Any other information on results incl. tables

Table 1: Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex			Total
		Rabbit #1	Rabbit #2	Rabbit #3
Erythema/Eschar Formation	1 hour	0	1	1	2
	24 hours	1	1	2	4
	48 hours	1	1	2	4
	72 hours	1	0	1	2
	7 days	0	0	0	0
Oedema Formation	1 hour	0	0	1	1
	24 hours	0	1	2	3
	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): 9

Primary Irritation Index (S/6): 9/6 = 1.5

Transcutaneous Electrical Resistance Assay

After a test material contact time of 24 hours, the mean electrical resistance was determined as 17.6 (± 7.3) kΩ. The test material was considered not to be corrosive to the skin in vivo.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is not considered to be irritating to the skin of rabbits.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. Three female rabbits were used. The test material was moisted with distilled water prior to application to the clipped flank of the rabbits.

Irritation was scored according to the method of Draize (1977). A semi-occlusive dressing was used. The study was performed in accordance with the OECD 404 and EU Method B.4 guidelines.

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 to slight oedema. One treated skin site appeared normal at the 72-hour observation and the remaining two treated skin sites appeared normal at the 7-day observation. 3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

The test material is therefore not considered to be irritating to the skin of rabbits.