Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 February 2004 to 10 march 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Annex V
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of inspection: 2 December 2002 Date of Signature: 13 February 2003

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TIPX
- Substance type: Colourless liquid.
- Physical state: Liquid.
- Lot/batch No.: 042028.
- Storage condition of test material: Approximately 4ºC in the dark.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, United Kingdom.
- Age at study initiation: 12 to 20 weeks old.
- Weight at study initiation: 2.0 to 3.5 kg.
- Housing: The animals were individually housed in suspended metal cages.
- Diet: Certified Rabbit Diet (Code 5322, supplied by BCM IPS Limited, London, United Kingdom) ad libitum throughout the study.
- Water: Mains drinking water ad libitum throughout the study.
- Acclimation period: At least 5 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml (as supplied).
Duration of treatment / exposure:
4 hours.
Observation period:
Up to 14 days (1 h, 24 h, 48 h, 72 h, 7 days and 14 days.)
Number of animals:
3.
Details on study design:
TEST SITE
- Area of exposure: Back (dorsal/flank).
- Type of wrap if used: Test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset.


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: 4 hours.


SCORING SYSTEM: the test sites were examined for evidence of primary irritation and scored according to the grading in the test guideline. The results were interpreted under EU classification system.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
120 Male
Time point:
other: mean at 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: The highest score of 2 was observed at 24, 48 and 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
121 Male
Time point:
other: mean at 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: The highest score of 2 was observed at 24, 48 and 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
89 Male
Time point:
other: mean at 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: The highest score of 2 was observed at 24, 48 and 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
120 Male
Time point:
other: mean at 24, 48 and 72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: The highest score of 2 was observed at 24 hours
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
121 Male
Time point:
other: mean at 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: The highest score of 2 was observed at 24, 48 and 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
89 Male
Time point:
other: mean at 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: The highest score of 2 was observed at 24, 48 and 72 hours
Irritant / corrosive response data:
See the table below. The test material to the intact skin of three rabbits produced erythema and oedema which were fully reversible within 14 days.
Other effects:
Loss of skin elasticity was noted at all treated skin sites at the 72-hour observation. Crust formation, which prevented evaluation of erythema and oedema, was noted at all treated skin sites at the 7-day observation.


All the treated skin sites appeared normal at the 14-day
observation.

Any other information on results incl. tables

Table Individual Skin Reactions

Skin Reaction Observation Time Individual Scores – Rabbit Number and Sex Total
120 Male 121 Male 89 Male 
Erythema/Eschar Formation 1 Hour 1 1 1 (3)
24 Hours 2 2 2 6
48 Hours 2 2 2 (6)
72 Hours 2Le 2Le 2Le 6
7 Days ?eCf ?eCf ?eCf (0-12)
  14 Days 0 0 0 (0)
Oedema Formation 1 Hour 1 1 1 (3)
24 Hours 2 2 2 6
48 Hours 1 2 2 (5)
72 Hours 1 2 2 5
7 Days ?0d ?0d ?0d (0-12)
  14 Days 0 0 0 (0)
Sum of 24 and 72-hour Readings (S):             23
(   ) = Total values not used for calculation of primary irritation index
Le = Loss of skin elasticity
Cf = Crust formation
?e = Adverse reaction prevented evaluation of erythema
?od = Adverse reaction prevented evaluation of oedema

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is classified as R38 Irritating to skin under Council Directive 67/548/EEC but does not meet the criteria under Regulation (EC) No 1272/2008.
Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

§        Commission Directive 92/69/EEC method B4 Acute Toxicity (Skin Irritation)

 

Results. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced erythema and oedema. Other skin reactions noted were loss of skin elasticity and crust formation. All treated skin site appeared normal at the 14-day observation.

 

Conclusion. The test material is classified as R38 Irritating to skin under Council Directive 67/548/EEC and as but does not meet the criteria under Regulation (EC) No 1272/2008.