Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 November 1994 and 5 November 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

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)
Remarks:
The work described was performed in compliance with the UK Principles of Good Laboratory Practice (The united Kingdom Compliance Programme. Department of Health 1989)

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Rabbits were supplied by David Percival Ltd. Moston. Sandbach. Cheshire. UK.
- Age at study initiation: Twelve to twenty weeks old
- Weight at study initiation: Animals weighed 2.23 to 2.51kg and were approximately twelve to twenty weeeks old.
- Housing:Animals were individually housed in suspended metal cages.
- Diet (e.g. ad libitum): Free access to mains drinking water and food (STANRAB SQC Rabbit Diet. Special Diets Services Ltd. Witham. Essex. UK) was allowed throughout the study.
- Water (e.g. ad libitum):Free access to mains drinking water and food (STANRAB SQC Rabbit Diet. Special Diets Services Ltd. Witham. Essex. UK) was allowed throughout the study.
- Acclimation period: Seven days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animal room maintained a temperature of 17 to 20°C.
- Humidity (%): 58 to 65%
- Air changes (per hr): Rate of air exchange was approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light):Lighting controlled by a time switch to give 12 hours continuous light and 12 hours darkness.


IN-LIFE DATES: From: Day 0 To: Day 3

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: A contralateral area of untreated skin was identified on each rabbit to serve as the control against which the reactions of the untreated site were evaluated.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A quantity of 0.5ml of the test material was introduced under a 2.5cm x 2.5cm cotton gauze patch.
- Concentration (if solution):No Data


VEHICLE
- Amount(s) applied (volume or weight with unit):Not applicable
- Concentration (if solution):Not applicable
- Lot/batch no. (if required): Not applicable
- Purity:Not applicable
Duration of treatment / exposure:
4 Hours
Observation period:
Thirty minutes following the removal of the patches and approximately 24, 48 and 72 hours after patch removal, the test sites were examined for evidence of primary irritation and scored.
Number of animals:
6 Rabbits
Details on study design:
TEST SITE
- Area of exposure: The back of each rabbit.
- % coverage: 2.5cm by 2.5cm cotton gauze patch.
- Type of wrap if used: 2.5cm by 2.5cm cotton gauze patch and placed in position with a strip of porous tape ( Micropore surgical tape, 3M Health care, Loughborough, England)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits. The control sites were similarly swabbed.
- Time after start of exposure: 4 hours.


SCORING SYSTEM:
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 oedema..................................................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 1 millimetre and extending beyond the area of exposure)...........4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72h
Score:
0.25
Reversibility:
no data
Remarks on result:
other: No corrosive effects were noted.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72h
Score:
0.1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Score:
0
Reversibility:
no data
Irritant / corrosive response data:
Please see attached tables 1-3.
Other effects:
Not applicable.

Any other information on results incl. tables

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 oedema.....................................................................................................................

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 1 millimetre and extending beyond the area of exposure).......................................................................................................................................

4

Any other skin reactions, if present, were also recorded.

Calculation of Primary Irritation Index. (FIFRA Data Reporting Guidelines)

The values for erythema and oedema for each animal at the 30 minute, 24, 48 and 72 -hour readings were totalled for the six test rabbits and each total was divided by 4 to give a score for each animal. The total of these scores was divided by 6 to give the primary irritation index of the test material.

Calculation of scores according to Annex VI of Council Directive 67/548/EEC. Relating to the classification, Packaging and Labelling of Dangerous Substances.

The values for erythema and oedema for each animal at the 24, 48 and 72 hour readings were totalled for the six test animals and the total scores divided by 18 to give a mean value for erythema and a mean value for oedema.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material. Alkane 2. produced a primary irritation index of 0.25 calculated according to FIFRA data reporting guidelines. No corrosive effects were noted. The test material produced mean scores of 0.1 for erythema/eschar formation and 0.0 for oedema according to EC labelling regulations.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit.

The study was designed to comply with the requirements of the U.S. Environmental Protection Agency (EPA) Guidelines, the OECD Guidelines for testing of chemicals No.404 "Acute Dermal Irritation/ Corrosion" .

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by commission Directive 93/21/EEC).

A single 4 -hour, semi-occluded application of the test material to the intact skin of six rabbits produced very slight erythema at four treated skin sites 30 minutes after patch removal. Very slight erythema persisted at two treated skin sites at the 24 -hour observation. All treated skin sites appeared normal at the 48 -hour observation.

The test material produced mean scores of 0.1 for erythema/eschar formation and 0.0 for oedema according to EC labelling regulations.