Registration Dossier

Diss Factsheets

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:
The study was performed between 16 July 2008 and 17 July 2008
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 no effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP standards (Schedule 1, Good Laboratory Practice Regulations 1999 (SI 1999/3106 as amended by SI 2004/0994))

Test material

Constituent 1
Chemical structure
Reference substance name:
Lithium Nickel Cobalt Aluminium Oxide
EC Number:
700-042-6
Cas Number:
177997-13-6
Molecular formula:
LiNiCoAlO2 where stoichiometry of Ni+Co+Al equals 1 and ranges are Li = 0.9 – 1.3, Co = 0.01 – 0.2, Ni = 0.75 – 0.99 and Al = 0.01 – 0.2
IUPAC Name:
Lithium Nickel Cobalt Aluminium Oxide

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: One New Zealand White rabbit was supplied by Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: 12 to 20 weeks old.
- Weight at study initiation: 3.41 kg
- Housing: The animal was housed in a suspended cage.
- Diet (e.g. ad libitum): Free access to food (Certified Rabbit Diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped free of fur
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test material, moistened with 0.5 ml of distilled water

Duration of treatment / exposure:
A single 3-minute semi-occluded application of the test material and a single 1-hour semi-occluded application.
Observation period:
24 hours
Number of animals:
1
Details on study design:
Procedure:
On the day before the test the rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers.
Two suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, 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 for the duration of the exposure period.
One patch was removed at each of two time points: 3 minutes and 1 hour after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
Due to the corrosive reactions following an exposure period of 1-hour, the 4 hour exposure period was not investigated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 24 hours
Remarks on result:
other: 3- minute exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: within 24 hours
Remarks on result:
other: 3-minute exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Remarks on result:
other: test was terminated after 24h
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Remarks on result:
other: test was terminated after 24h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
0
Max. score:
0
Remarks on result:
other: 3-minute exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 24 hours
Remarks on result:
other: 3-minute exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Remarks on result:
other: test was terminated after 24h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Remarks on result:
other: test was terminated after 24h
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 1-hour exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
>= 0 - <= 4
Reversibility:
not reversible
Remarks on result:
other: 1-hour exposure - adverse reaction prevents accurate evaluation of erythema
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 hour
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: 1-hour exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
>= 0 - <= 4
Reversibility:
not reversible
Remarks on result:
other: 1-hour exposure - Adverse reaction prevents accurate evaluation of oedema
Irritant / corrosive response data:
3-Minute Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 1.
Very slight erythema was noted at the treated skin site one hour after patch removal. A small area of petechial haemorrhage was also noted at the left and right edges of the treated skin site at this observation. Well defined erythema and very slight oedema were noted at the treated skin site at the 24 hour observation. A small dark coloured scab, approximately 4 mm x 4 mm in size, was also noted on the right edge of the treated skin site at this observation.

1-Hour Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 1.
Reactions noted at the treated skin site one hour after patch removal were green coloured dermal necrosis (attributed a Draize score of 4 for injuries in depth), surrounded by dermal haemorrhage, and slight oedema. A sunken, hardened dark brown/black coloured scab, preventing accurate evaluation of erythema and oedema, was noted at the treated skin site at the 24 hour observation.
Other effects:
None.

Any other information on results incl. tables

Table1               Individual Skin Reactions Following 3-Minute and 1-Hour Exposures

Skin Reaction

Observation Time

Individual Scores - Rabbit Number and Sex

67601 Male

3-Minute Exposure

1-Hour Exposure

Erythema/Eschar Formation

1 Hour

1Hd

4NHd*

24 Hours

2St

?eSu

Oedema Formation

1 Hour

0

2

24 Hours

1

?od

 

 


N= Green coloured dermal necrosis

Hd = Small area of petechial haemorrhage on left and right edges of test site

Hd* = Dermal haemorrhage surrounding dermal necrosis

St = Small dark coloured scab, approximately 4 mm x 4 mm, on the right edge of test site

Su = Sunken, hardened dark brown/black coloured scab

?e = Adverse reaction prevents accurate evaluation of erythema

?od = Adverse reaction prevents accurate evaluation of oedema

Due to the corrosive reactions following an exposure period of 1-hour, the 4‑hour exposure period was not investigated.

The animal was killed for humane reasons immediately after the 24-hour observation, due to the irreversible effects, in accordance with Company policy and current UK Home Office guidelines.

The test material was classified as CORROSIVE to rabbit skin (based on one rabbit only).

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was classified as CORROSIVE to rabbit skin (based on one rabbit only).
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)

§        Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC

Results. 

A single 3-minute semi-occluded application of the test material to the intact skin of one rabbit produced no corrosive effects.

A single 1-hour, semi-occluded application of the test material to the intact skin of one rabbit produced reactions indicative of dermal corrosion. The reactions included green coloured dermal necrosis and scabbing.

The animal was killed for humane reasons immediately after the 24-hour observation, due to the irreversible effects, in accordance with Company policy and current UK Home Office guidelines.

Due to the corrosive reactions following an exposure period of 1-hour, the 4-hour exposure period was not investigated.

Conclusion. 

The test material was classified as corrosive to rabbit skin (based on one rabbit only).

Categories Display