Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25-02-2014 to 10-10-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
inspected: July 2012; signature: November 2012

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Liquid
- Storage condition of test material: approximately 4°C in the dark under nitrogen
- Other: clear colourless

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf: NZW
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.72 to 2.86 g
- Housing: Individually housed in cages with perforated floors, with shelters and cage enrichment
- Diet (ad libitum): Global Diet 2930C (Recognised Supplier); provided ad libitum
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 25-02-2014 To: 28-02-2014

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL.
- Concentration (if solution): Not applicable.

VEHICLE
- Amount applied: 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:
72 hours (initial observation); additional observations are typically made daily up to Days 7 and 14 to assess the reversibility of skin reactions (as appropriate).
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: Dorsal (2.5 cm x 2.5 cm cotton gauze patch secured with adhesive tape)
- % coverage: Not reported
- Type of wrap if used: cotton gauze patch secured with adhesive tape elastic corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: Four hours after the application, the dressing was removed by gentle swabbing with cotton wool soaked in distilled water.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1 hour, 4 hours, 24 hours, 48 hours and 72 hours. Additional observations daily up to 7 or 14 days, as appropriate

SCORING SYSTEM: consistent with Draize Scale:
- Method of calculation:
Erythema and eschar formation:
No erythema .......................................................................................................................... 0
Very slight erythema (barely perceptible) ............................................................................... 1
Well-defined erythema ........................................................................................................... 2
Moderate to severe erythema................................................................................................. 3
Severe erythema (beet redness) *.......................................................................................... 4
*. to eschar formation preventing grading of erythema
Oedema formation:
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 millimeter) ........................................................... 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Very slight erythema and very slight edema were noted at all treated skin sites immediately after patch removal (at 1 hour). All treated skin sites appeared normal one hour after patch removal.
Other effects:
- Other adverse local effects: None.
- Other adverse systemic effects: All males showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 1.0 : Individual Scores and Mean Scores following 4-hour exposure

Skin Reaction

Reading (hours)

1# Male

#2 Male

3# Male

Erythema/Escar Formation

24

0

0

0

 

48

0

0

0

 

72

0

0

0

 

Total

0.0

0.0

0.0

 

Mean

0.0

0.0

0.0

Oedema Formation

24

0

0

0

 

48

0

0

0

 

72

0

0

0

 

Total

0.0

0.0

0.0

 

Mean

0.0

0.0

0.0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test item is not considered to be irritating to the skin.
Executive summary:

The study was performed to OECD TG 404 and EU Method B.4 guidelines in accordance with GLP to assess the primary skin irritancy potential of the test item in New Zealand White rabbits. Three rabbits were exposed for 4-hour by semi-occluded application of the test item to the intact clipped skin with 0.5 mL test item introduced under a 2.5 cm x 2.5 cm semi-occlusive patch. The patch was secured in position with adhesive tape and elasticated corset. After exposure to the test item the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. Very slight erythema (score = 1) and very slight oedema (score = 1) was observed in the treated skin at 1 hour. Mean scores following grading at 24, 48 and 72h were zero in all scoring criteria. Under the conditions of the study, the test item is not considered to be a skin irritant.