Registration Dossier

Diss Factsheets

Administrative data

Description of key information

- Skin irritation: not irritating, by analogy with Cerium and iron oxide isostearate (Active matter of DPX10)

- Eye irritation: not irritating, by analogy with Cerium and iron oxide isostearate (Active matter of DPX10)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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
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)
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)
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
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.

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

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.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Data from cerium and iron oxide isosterate, a substance that presents structural similarities with iron oxide isostearate, was used to cover this endpoint. See the Read-across justification document (Justification for analogue approach) attached in IUCLID Section 13.2 for the justification of the read-across.
See also the original letters from the French Competent Authorities requiring the read across to be done with Cerium and iron oxide isostearate substances, attached in Section 13.2 as well (French CA testing program July 2005, and French CA testing program Sep 2007).
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal: 883
Time point:
24 h
Score:
2
Remarks on result:
other:
Remarks:
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:
Remarks:
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:
Remarks:
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:
Remarks:
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:
Remarks:
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
Irritation parameter:
erythema score
Basis:
animal: 836
Time point:
72 h
Score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other:
Remarks:
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
Interpretation of results:
GHS criteria not met
Conclusions:
Cerium and iron oxide isostearate, an analogue of iron oxide isostearate, is not considered to be a skin irritant in the rabbit. Based on the stuctural similarities between traget and sources substances, the same conclusion is assumed for iron oxide isostearate.
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, a structural analogue of 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 cerium and iron oxide isostearate 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 UN/EU GHS. The same is assumed for iron oxide isostearate based on structural similarities between the 2 substances.

 

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye 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
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
temperature and relative humidity were sometimes out of the target (minor deviations)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France.
- Age at study initiation: data not available.
- Weight at study initiation: 2.5 ± 0.4 kg.
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet: free access to 110 pelleted diet.
- 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 6 september 2001 (first treatment) to 9 September 2001 (end of the observation period)
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg
- Concentration: undiluted
Duration of treatment / exposure:
Single conjunctival instillation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

OBSERVATION TIME POINTS
Reading of the scores were performed at 1h, 24, 48 and 72h after the instillation.

SCORING SYSTEM:
Ocular reactions were scored according to the following numerical scale:
CONJUNCTIVAL LESIONS AND DISCHARGE:
> Chemosis (lids and/or nictitating membranes)
. no swelling = 0
. any swelling above normal (includes nictitating membranes) = 1
. obvious swelling with partial eversion of lids = 2
. swelling with lids about half-closed = 3
. swelling with lids more than half-closed = 4
> Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
. blood vessels normal = 0
. a number of blood vessels definitely hyperemic (injected) = 1
. diffuse, crimson colour, individual vessels not easily discernible = 2
. diffuse, beefy red = 3
> Discharge
. absence of discharge = 0
. slight discharge (does not include small amounts normally found in inner canthus) = 1
. discharge with moistening of lids and hairs adjacent to lids = 2
. discharge with moistening of lids and hairs on wide area around the eye = 3
IRIS LESIONS:
. normal = 0
. markedly deepened rugae, congestion, swelling, moderate circum-corneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) = 1
. no reaction to light, haemorrhage, gross destruction (any or all of these) = 2
CORNEAL LESIONS:
> Degree of opacity (area most dense taken for reading)
. no ulceration or opacity = 0
. scattered or diffuse areas of opacity (other than slight dulling or normal lustre), details of iris clearly visible = 1
. easily discernible translucent area, details of iris slightly obscured = 2
. nacreous areas, no details of iris visible, size of pupil barely discernible = 3
. opaque cornea, iris not discernible through the opacity = 4
> Area of opacity
. one quarter (or less) but not zero = 1
. greater than one quarter but less than a half = 2
. greater than one half but less than three quarters = 3
. greater than three quarters up to whole area = 4
Any other lesions observed were noted.
TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: mean of the 3 time points
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: mean of the 3 time points
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: mean of the 3 time points
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other:
Remarks:
mean of the 3 time points
Irritation parameter:
other: discharge
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other:
Remarks:
mean of the 3 time points
Irritation parameter:
conjunctivae score
Basis:
animal: 883
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: 883
Time point:
48 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: 883
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: 835
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: 835
Time point:
48 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: 835
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: 836
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: 836
Time point:
48 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal: 836
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: 883
Time point:
24 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: 883
Time point:
48 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: 883
Time point:
72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: 836
Time point:
24 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: 836
Time point:
48 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: 836
Time point:
72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: 835
Time point:
24 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: 835
Time point:
48 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal: 835
Time point:
72 h
Score:
0
Max. score:
2
Irritation parameter:
cornea opacity score
Basis:
animal: 883
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: 883
Time point:
48 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: 883
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: 836
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: 836
Time point:
48 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: 836
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: 835
Time point:
24 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: 835
Time point:
48 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: 835
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal: 883
Time point:
24 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: 883
Time point:
48 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: 883
Time point:
72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: 836
Time point:
24 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: 836
Time point:
48 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: 836
Time point:
72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: 835
Time point:
24 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: 835
Time point:
48 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal: 835
Time point:
72 h
Score:
0
Max. score:
3
Irritant / corrosive response data:
Very slight conjunctival reactions were noted on day 1, 1 hour after the conjonctival instillation: a very slight chemosis (grade 1), a very slight redness of the conjunctiva (grade 1) and a clear discharge were observed in all animals. No more conjunctival effects were observed at the 24 hour reading time.
No other ocular reactions were noted during the study.

Summary of the observed ocular irritation scores (3 rabbits):

 Time after instillation   

 1 hour

 24 hrs

 48 hrs

 72 hrs

 Rabbit No.   

 883

 835

 836

 883

 835

 836

 883

 835

 836

 883

 835

 836

 Conjunctiva

 Chemosis

1

1

1

0

0

0

0

0

0

0

0

0

 

 Discharge

1

1

1

0

0

0

0

0

0

0

0

0

 

 Redness

1

1

1

0

0

0

0

0

0

0

0

0

 Iris   

0

0

0

0

0

0

0

0

0

0

0

0

 Cornea

 Opacity

0

0

0

0

0

0

0

0

0

0

0

0

 

 Surface

0

0

0

0

0

0

0

0

0

0

0

0

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

In a primary eye irritation study performed according to OECD 405 and GLP (CIT report No. 22321 TAL), scored as validity 1 according to Klimisch criteria, 100 mg of cerium and iron oxide isostearate were instilled into the conjunctival sac of the right eye of 3 male New Zealand White rabbits. Exposed eyes were not washed. Animals then were observed for 72 hours. Irritation was scored 1, 24, 48 and 72 hours after instillation by calculating ocular irritation scores, based on the grading of conjunctiva, iris and cornea scores. 

Very slight conjunctival reactions (very slight chemosis and very slight redness of the conjunctiva; clear discharge) were observed in all animals on day 1.

No other ocular reactions were noted during the study.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for chemosis, 0.0, 0.0 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity.

 

The test substance was considered as non-irritant to the eye. No classification for eye irritation is warranted based on the ocular reactions observed during 72 hours after 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 405 guideline requirements for acute eye irritation or corrosion.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Data from cerium and iron oxide isosterate, a structural analogue of iron oxide isostearate, was used to cover this endpoint. See the Read-across justification document (Justification for analogue approach) attached in IUCLID Section 13.2 for the justification of the read-across.
See also the original letters from the French Competent Authorities requiring the read across to be done with Cerium and iron oxide isostearate substances, attached in Section 13.2 as well (French CA testing program July 2005, and French CA testing program Sep 2007).
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
other: discharge
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Interpretation of results:
GHS criteria not met
Conclusions:
Cerium and iron oxide isostearate is not considered to be an eye irritant in the rabbit. Due to structural similarities between the 2 substances, the same conclusion is assumed for iron oxide isostearate.
Executive summary:

In a primary eye irritation study performed according to OECD 405 and GLP (CIT report No. 22321 TAL), scored as validity 1 according to Klimisch criteria, 100 mg of cerium and iron oxide isostearate, a structural analogue to iron oxide isostearate, were instilled into the conjunctival sac of the right eye of 3 male New Zealand White rabbits. Exposed eyes were not washed. Animals then were observed for 72 hours. Irritation was scored 1, 24, 48 and 72 hours after instillation by calculating ocular irritation scores, based on the grading of conjunctiva, iris and cornea scores. 

Very slight conjunctival reactions (very slight chemosis and very slight redness of the conjunctiva; clear discharge) were observed in all animals on day 1.

No other ocular reactions were noted during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for chemosis, 0.0, 0.0 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity.

 

The test substance cerium and ison oxide isostearate was considered as non-irritant to the eye. No classification for eye irritation is warranted based on the ocular reactions observed during 72 hours after exposure, according to the criteria of UN/EU GHS.

The same conclusion is assumed for iron oxide isostearate, based on structural similarities between the 2 substances.

 

This study is classified as acceptable. It satisfies the OECD 405 guideline requirements for acute eye irritation or corrosion.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no data available on the test item, but the skin irritation and eye irritation potential of iron oxide isostearate was assessed by analogy with cerium and iron oxide isostearate (Active matter DPX10, CAS 753480-32-9) in accordance with the testing program established by the Competent Authorities in July 2005 (see document "050721-AC-Programme études-DPX13.pdf" attached in section 13.2 and the Read-across justification document attached in this section as well):

In a primary dermal irritation study performed according to OECD 404 and GLP (CIT report No. 22320 TAL, 2001), scored as validity 1 according to Klimisch criteria and thus selected as Key study, 3 male New Zealand White rabbits were dermally exposed to 0.5g of cerium and iron oxide isostearate (Active matter of DPX10, CAS 753480-32-9) applied on the skin and maintained under semi-occlusive dressing for 4 hours. Animals then were observed for up to 7 days. Irritation (erythema and edema) was scored 1, 24, 48, 72 h and on days 5, 6 and 7 after removal of the dressing.

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.

According to these results, the test item is not classified as a skin irritant according to EU criteria. The same is assumed for iron oxide isostearate.

In a primary eye irritation study performed according to OECD 405 and GLP (CIT report No. 22321 TAL, 2001), scored as validity 1 according to Klimisch criteria and thus considered as the Key study, 100 mg of cerium and iron oxide isostearate (Active matter of DPX10, CAS 753480-32-9) were instilled into the conjunctival sac of the right eye of 3 male New Zealand White rabbits. Exposed eyes were not washed. Animals then were observed for 72 hours. Irritation was scored 1, 24, 48 and 72 hours after instillation based on the grading of conjunctiva, iris and cornea effects. 

Very slight conjunctival reactions (very slight chemosis and very slight redness of the conjunctiva; clear discharge) were observed in all animals on day 1. No other ocular reactions were noted during the study.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for chemosis, 0.0, 0.0 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity.

According to these results, the test item is not classified as an eye irritant according to EU criteria. Same results and therefore no classification is assumed also for iron oxide isostearate.

Justification for classification or non-classification

Based on the classification criteria of UN/EU GHS, the low level of dermal irritation and the absence of ocular irritation in rabbits (by analogy with cerium and iron oxide isostearate) resulted in no classification of iron oxide isostearate for skin and eye irritation.