Tar acids (shale oil), C6-9-fraction, alkylphenols

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 March 2004 - 08 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

5-methylresorcinol

EC Number:

207-984-2

EC Name:

5-methylresorcinol

Cas Number:

504-15-4

Molecular formula:

C7H8O2

IUPAC Name:

5-methylbenzene-1,3-diol

Constituent 2

Reference substance name:

Resorcinol

EC Number:

203-585-2

EC Name:

Resorcinol

Cas Number:

108-46-3

Molecular formula:

C6H6O2

IUPAC Name:

benzene-1,3-diol

Constituent 3

Reference substance name:

2,5-dimethylresorcinol

EC Number:

207-688-3

EC Name:

2,5-dimethylresorcinol

Cas Number:

488-87-9

Molecular formula:

C8H10O2

IUPAC Name:

2,5-dimethylbenzene-1,3-diol

Constituent 4

Reference substance name:

2-methylresorcinol

EC Number:

210-155-8

EC Name:

2-methylresorcinol

Cas Number:

608-25-3

Molecular formula:

C7H8O2

IUPAC Name:

2-methylbenzene-1,3-diol

Constituent 5

Reference substance name:

4-methylresorcinol

EC Number:

207-827-8

EC Name:

4-methylresorcinol

Cas Number:

496-73-1

Molecular formula:

C7H8O2

IUPAC Name:

4-methylbenzene-1,3-diol

Constituent 6

Reference substance name:

4,5-dimethylbenzene-1,3-diol

EC Number:

610-895-5

Cas Number:

527-55-9

Molecular formula:

C8H10O2

IUPAC Name:

4,5-dimethylbenzene-1,3-diol

Constituent 7

Reference substance name:

5-ethylbenzene-1,3-diol

Cas Number:

4299-72-3

Molecular formula:

C8H10O2

IUPAC Name:

5-ethylbenzene-1,3-diol

Constituent 8

Reference substance name:

2-ethyl-5-methylbenzene-1,3-diol

Cas Number:

27465-63-0

Molecular formula:

C9H12O2

IUPAC Name:

2-ethyl-5-methylbenzene-1,3-diol

Constituent 9

Reference substance name:

5-ethyl-2-methylbenzene-1,3-diol

Cas Number:

34745-52-3

Molecular formula:

C9H12O2

IUPAC Name:

5-ethyl-2-methylbenzene-1,3-diol

Constituent 10

Reference substance name:

2,4,5-trimethylbenzene-1,3-diol

Cas Number:

20427-81-0

Molecular formula:

C9H12O2

IUPAC Name:

2,4,5-trimethylbenzene-1,3-diol

Constituent 11

Reference substance name:

2,4-dimethylresorcinol

EC Number:

211-213-5

EC Name:

2,4-dimethylresorcinol

Cas Number:

634-65-1

Molecular formula:

C8H10O2

IUPAC Name:

2,4-dimethylbenzene-1,3-diol

Constituent 12

Reference substance name:

Phenol

EC Number:

203-632-7

EC Name:

Phenol

Cas Number:

108-95-2

Molecular formula:

C6H6O

IUPAC Name:

phenol

Constituent 13

Reference substance name:

Cresol

EC Number:

215-293-2

EC Name:

Cresol

Cas Number:

1319-77-3

Molecular formula:

C7H8O

IUPAC Name:

cresol

Constituent 14

Reference substance name:

not applicable

Molecular formula:

not applicable

IUPAC Name:

not applicable

Test material form:

liquid

Details on test material:

Sponsor's identification: Total shale oil phenols
Description: dark brown extremely viscous liquiy
Batch number: Part No. 3
Date received: 30 January 2004
Storage conditions: room temperature, in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

One New Zealand White rabbit was supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK. At the start of the study the animal was in the weight range of 2.0 to 3.5 kg and was twelve to twenty weeks old. After an acclimatisation period of at least five days the animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animal was individually housed in a suspended metal cage. Free access to mains drinking
water and food (Certified Rabbit Diet (Code 5322) supplied by BCM IPS Limited, London, UK)
was allowed throughout the study. The diet and drinking water were considered not to contain
any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70%
respectively. Any occasional deviations from these targets were considered not to have affected
the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per
hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00
to 18:00) and twelve hours darkness.

The animal was 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.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 mL of test substance

Duration of treatment / exposure:

4 hours

Observation period:

1 hour, 24 hours, 48 hours, 72 hours, 7 days, 14 days

Number of animals:

1

Details on study design:

On the day before the test the rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were
selected for the study. One rabbit was treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 ml of the test material 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.

One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
After consideration of the skin reactions produced in the first animal, no further animals were treated.
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 anf scored according to the following scale:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema: 4

Oedema Formation Value
NO edema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than | millimetre and extending beyond the area of EXPOSULE): 4
Any other skin reactions, if present, were also recorded.
Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: dark brown-coloures dermal necrosis over whole of treatment site

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Reversibility:

not specified

Remarks on result:

not determinable

Remarks:

Unable to score for erythema due to dark brown-coloured staining and blanching

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Reversibility:

not specified

Remarks on result:

not determinable

Remarks:

Unable to score for erythema due to dark brown-coloured staining and blanching

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Max. score:

4

Reversibility:

not specified

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: oedema extending ventrally below treatment site

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Reversibility:

not specified

Remarks on result:

not determinable

Remarks:

Adverse reaction prevent evluation of oedema

Results 7

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Reversibility:

not specified

Remarks on result:

not determinable

Remarks:

Adverse reaction prevent evluation of oedema

Any other information on results incl. tables

Dark brown-coloured staining was noted at the treated skin site throughout the study.

Dark brown-coloured staining and blanching of the skin, both of which prevented evaluation of erythema, were noted at the treated skin site one hour after patch removal. Well-defined erythema around the treated skin site was also noted one hour after patch removal. Dark brown-coloured dermal necrosis (attributed a Draize score of 4 for injuries in depth), light brown discolouration of the epidermis, loss of skin elasticity and flexibility and well-defined erythema surrounding other skin reactions were noted at the treated skin site at the 24-hour observation. A hardened dark brown/black-coloured scab, undulating in appearance, was noted at the treated skin site at the 48, 72-hour and 7 and 14-day observations with well-defined erythema surrounding other skin reactions also noted at the 48-hour observation and scab lifting to reveal glossy skin also noted at the 14-day observation.

Moderate oedema was noted at the treated skin site one hour after patch removal with severe oedema, extending ventrally below the treatment site, at the 24-hour observation.

The reactions noted at the treated skin site at the 48-hour and subsequent observations prevented the evaluation of erythema and oedema.

The reactions were considered to be indicative of dermal corrosion.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Executive summary:

A single 4-hour, semi-occluded application of the test material to the intact skin of one rabbit produced reactions indicative of dermal corrosion including blanching of the skin, well- defined erythema surrounding treatment site, dark brown necrosis, hardened dark brown/black-coloured scabs, scabs lifting to reveal glossy skin, scab undulating, loss of skin elasticity and flexibility and oedema extending ventrally below treatment site. On occasions the reactions noted precluded the evaluation of erythema and oedema.

Conclusion:

The test material was classified as corrosive to rabbit skin.