Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
26th April - 12th August 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
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. Study conducted on middle weight fraction of shale oils.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
68308-34-9
Cas Number:
68308-34-9
IUPAC Name:
68308-34-9
Constituent 2
Reference substance name:
Shale oils
EC Number:
269-646-0
EC Name:
Shale oils
IUPAC Name:
269-646-0
Constituent 3
Reference substance name:
Shale Oils
IUPAC Name:
Shale Oils
Details on test material:
Identification: Shale oil, middle fraction
Description :Liquid
Batch number: 1
Purity min.: 99 %
Composition: Complex mixture of hydrocarbons and oxygen compounds
Stability of test item: Stable under storage conditions
Expiry date: 04-MAR-2006
Storage conditions: At room temperature (range of 20 ± 5 °C), light protected.
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, BP 0109, F-69592, L’Arbresle
- Age at study initiation: 14 weeks (male), 12-13 weeks (females)
- Weight at study initiation: NDA
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 26th April - 2nd May 2005

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
- Other: Music was played during the daytime light period.

IN-LIFE DATES: From: 26th April 2005 To: 17th May 2005

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml shale oil
- Concentration (if solution): N/A

VEHICLE
N/A
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: NDA
- Type of wrap if used: Shale oil was placed on a surgical gauze patch. This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with luke warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM:

The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004, approximately 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after the removal of the dressing, gauze patch and test item.
To allow further examination of the test site, one animal was re-clipped on completion of the 10-day examination.
If evident, corrosive or staining properties of the test item were described and recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 28
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
animal: 29
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal: 30
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal: 28
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal: 29
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal: 30
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritant / corrosive response data:
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 2.00, 1.00 and 2.00, respectively and the mean oedema score was 1.00 for all three animals, respectively. (see table 1)
Very slight to well-defined erythema were noted in all animals from the 1- to the 72-hour reading and very slight erythema persisted in two animals up to the 7-day examination.
Very slight swelling was observed in all animals from the 24- to the 72-hour reading and persisted in two animals up to the 7-day examination.
Scaling was noted in all animals from the 72-hour reading to the 10-day examination or to the end of the observation period.
No abnormal findings were observed on the treated skin of any animal 14 days after treatment except scaling, which was present in two animals from the 72-hour reading to the end of the observation time.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Slight brown staining produced by the test item of the treated skin was observed in all animals from the 1-hour reading up to the 7- or 10-day examination, respectively.

Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

The body weights of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004

Grading of Skin Reactions

ERYTHEMA AND ESCHAR FORMATION

No erythema.......................................................................................................................0

Very slight erythema............................................................................................................1

Well-defined erythema........................................................................................................2

Moderate to severe erythema.............................................................................................3

Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema) reading.................................................4

OEDEMA FORMATION

No oedema.........................................................................................................................0

Very slight oedema (barely perceptible)...............................................................................1

Slight oedema (edges of area well-defined by definite raising)...............................................2

Moderate oedema (edges raised approximately 1 mm).........................................................3

Severe oedema (raised more than 1 mm and extending beyond the area of exposure)............4

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean scores of the three rabbits combined at the mean of the 24, 48 and 72 hour time points was 1.67 for erythema and 1 for oedema. Scaling was present in all three animals at 72 hours, and still present in two at the end of the 14 day observation period. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), Shale oil is considered to be “irritating” to rabbit skin with respect to the scaling effects observed.
Executive summary:

The skin irritation potential of shale oils, medium was examined in an experiment according to OECD 404 and performed to GLP. Shale oils, heavy was applied to the torso of 2 female and 1 male New Zealand white rabbit, and held in place with a semi-occlusive dressing for 4 hours. After the exposure, the test substance was washed off and the rabbits were then observed for 14 days.

The mean scores of the three rabbits combined at the mean of the 24, 48 and 72 hour time points was 1.67 for erythema and 1 for oedema. Scaling was present in all three animals at 72 hours, and still present in two at the end of the 14 day observation period. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), Shale oil is considered to be “irritating” to rabbit skin with respect to the scaling effects observed.

Based on the rationale for read-across, it is considered acceptable to use this study to address the same endpoint for the heavy fraction of shale oil.