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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from August 2001 to 12 December 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
temperature and relative humidity were sometimes out of the target, and the initial body weight of one animal was slightly lower than 2.2kg (minor deviation)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
753480-32-9
Cas Number:
753480-32-9
IUPAC Name:
753480-32-9

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France.
- Age at study initiation: data not available.
- Weight at study initiation: 2.4 ± 0.2 kg (one animal was slightly lower: 2.194kg).
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet: 110 pellet diet (UAR, Villemoisson, Epinay-Sur-Orge, France), ad libitum.
- Water: filtered drinking water, ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C.
- Humidity: 30 to 70%.
- Air changes: approximately 12 cycles/hour.
- Photoperiod: 12 h light/12 h dark.

IN-LIFE DATES: from 28 August 2001 (first treatment) to 10 September 2001 (end of the observation period)

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration: undiluted
- Remark: the test substance was applied on a moistened gauze pad, in order to ensure a good contact with the skin.
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: data not available
- % coverage: data not available
- Type of wrap if used: gauze pad held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: yes (wiped off by means of a moistened gauze pad).
- Time after start of exposure: 4 hours.

OBSERVATION TIME POINTS
Reading of the skin erythema and oedema scores were performed after the removal of the dressing at 1h, 24, 48 and 72h, and then days 4, 5, 6 and 7 of the study.

SCORING SYSTEM:
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) to slight eschar formation (injuries in depth) -> 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 (raised approximately 1 millimetre) -> 3
. severe oedema (raised more than 1 millimetre and extending beyond area of exposure) -> 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
1.2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: No erythema was observed at 24/48/72 hours but as a brown coloration of the skin was noted due to the test substance which could have masked a possible erythema (grade 1 or 2), a possible maximal mean score was calculated for erythema (mean of 3 rabbits).
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal: 883
Time point:
24 h
Score:
2
Remarks on result:
other: brown coloration of the skin which could have masked a possible well-defined erythema
Irritation parameter:
erythema score
Basis:
animal: 883
Time point:
48 h
Score:
2
Remarks on result:
other: brown coloration of the skin which could have masked a possible well-defined erythema
Irritation parameter:
erythema score
Basis:
animal: 883
Time point:
72 h
Score:
1
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: brown coloration of the skin which could have masked a possible very slight erythema
Irritation parameter:
erythema score
Basis:
animal: 835
Time point:
24 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal: 835
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal: 835
Time point:
72 h
Score:
0
Reversibility:
fully reversible within: 1 day
Irritation parameter:
erythema score
Basis:
animal: 836
Time point:
24 h
Score:
2
Remarks on result:
other: brown coloration of the skin which could have masked a possible well-defined erythema
Irritation parameter:
erythema score
Basis:
animal: 836
Time point:
48 h
Score:
2
Remarks on result:
other: brown coloration of the skin which could have masked a possible well-defined erythema
Irritation parameter:
erythema score
Basis:
animal: 836
Time point:
72 h
Score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: brown coloration of the skin which could have masked a possible well-defined erythema
Irritation parameter:
edema score
Basis:
animal: 883
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 883
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 883
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 835
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 835
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 835
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 836
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 836
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 836
Time point:
72 h
Score:
0
Irritant / corrosive response data:
A brown coloration of the skin, due to the test substance, was observed in all animals; it could have masked a possible very slight or well-defined erythema (grade 1 or 2) in all three animals on day 1 and up to day 5 (one animal) or 6 (one animal).
No erythema and no oedema were observed.

However, taking into account the coloration of the test substance, the maximal mean scores over 24, 48 and 72 hours for each animal could possibly be 1.7, 0.0 and 2.0 for erythema.
The mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for oedema.
Other effects:
A brown coloration of the skin, due to the test substance, was observed in all animals.

Any other information on results incl. tables

Summary table of individual irritation scores:

Rabbit number

Dermal irritation

Scores

Mean irritation score

1h

24h

48h

72h

D5

D6

D7

883

Erythema

Oedema

Other

C

0

*

C

0

*

C

0

*

C

0

*

C

0

*

0

0

C

-

-

-

n.d.

0.0

835

Erythema

Oedema

Other

C

0

*

0

0

C

0

0

C

0

0

C

-

-

-

-

-

-

-

-

-

0.0

0.0

836

Erythema

Oedema

Other

C

0

*

C

0

*

C

0

*

C

0

*

C

0

*

C

0

*

0

0

C

n.d.

0.0

n.d. = not determined

* = None

C = brown coloration of the skin

- = examination not performed

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Cerium and iron oxide isostearate is not considered to be a skin irritant in the rabbit.
Executive summary:

In a primary dermal irritation study performed according to OECD 404 and GLP (CIT report No. 22320 TAL), scored as validity 1 according to Klimisch criteria, 3 male New Zealand White rabbits were dermally exposed to 0.5 g of cerium and iron oxide isostearate applied on the skin of flanks and maintained under semi-occlusive dressing for 4 hours. Animals then were observed for up to 7 days. Irritation was scored 1, 24, 48, 72 h and on days 5, 6 and 7 after removal of the dressing by calculating dermal irritation scores, based on the grading of cutaneous erythema and edema.

 

A brown coloration of the skin, due to the test substance, was observed in all animals and could have masked a possible very slight or well-defined erythema in all three animals on day 1 and up to day 5 (one animal) or 6 (one animal).No erythema and no oedema were observed.

However, taking into account the coloration of the test substance, the maximal mean scores over 24, 48 and 72 hours for each animal could possibly be 1.7, 0.0 and 2.0 for erythema.

The mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for oedema.

 

 

The test substance was considered as non-irritant to the skin. No classification for skin irritation is warranted based on the observed cutaneous reactions following a 4-hour exposure, according to the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.

 

This study is classified as acceptable. It satisfies the OECD 404 guideline requirements for acute dermal irritation or corrosion.