Registration Dossier

Administrative data

Description of key information

Several in vivo skin and eye irritating studies are available both with substance analogues yttrium oxide and europium oxide. None of the studies indicated skin effects and only slight eye irritation was seen, thus no further studies were performed. The results with the substance analogues are read-across to the substance. 

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in section 13.
Reason / purpose for cross-reference:
read-across source
GLP compliance:
not specified
Vehicle:
unchanged (no vehicle)
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
8
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritant / corrosive response data:
There were no signs of dermal irritation. Yttrium oxide is not considered to be a skin irritant.
Interpretation of results:
GHS criteria not met
Conclusions:
In a primary dermal irritation study, 6 New Zealand Albino rabbits were dermally exposed to 0.5 g of yttrium oxide (purity unknown) for 24 hours to ca. 2.5 cm² of one intact and one abraded skin site. Test sites were covered with an occlusive dressing for 24 hours. Animals were then observed for 3 days. Irritation was scored by the method of Draize. In this study, yttrium oxide is not a dermal irritant. This skin irritation study is classified as acceptable. It does satisfy the guideline requirement for a skin irritation study (16CFR 1500 -41) in the rabbit. This result is read across to yttrium oxide, europium-doped.
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
The rationale to read across the data is attached in section 13.
Reason / purpose for cross-reference:
read-across source
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
8
Remarks on result:
other: scored 24 and 72 hours after initial exposure
Irritant / corrosive response data:
No signs of dermal irritation

The justification of this analogue approach is described in a report, see section 13 of the IUCLID and in chapter 1.4 of the CSR.

Interpretation of results:
GHS criteria not met
Conclusions:
In an in vivo skin irritation study with europium oxide, the substance is considered to be not irritating to the skin. This result is read across to yttrium oxide, europium doped.
Executive summary:

In an in vivo skin irritation study, rabbits were exposed to a single dose of 0.5 g europium oxide via occlusive application to the intact and abraded skin for 24 hours. The rabbits were observed for 72 hours and scored according to Draize. The primary dermal irritation index was 0, therefore, based on this study the substance europium oxide is considered to be not irritating to the skin. This result is read across to yttrium oxide, europium doped.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1990
Justification for type of information:
The rationale to read across these data is attached in section 13.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 rabbits (with unwashed eye)
Time point:
24 h
Score:
5.3
Max. score:
110
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Scores decreased significantly from 24 to 48 and to 72 hours. At 72 hours score was only 0.7, showing reversibility.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 rabbits (with washed eye)
Time point:
24 h
Score:
7.3
Max. score:
110
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Scores decreased significantly from 24 to 48 and to 72 hours. At 72 hours score was only 0.7, showing reversibility.
Irritant / corrosive response data:
- Individual (total) scores are not available. Only the mean of the 3 rabbits: no further details are available.
- Mean scores for unwashed eyes at 24, 48 and 72 hours were 5.3, 3.3 and 0.7, respectively
- Mean scores for washed eyes at 24, 48 and 72 hours were 7.3, 2.0 and 0.7, respectively
Interpretation of results:
GHS criteria not met
Conclusions:
In an in vivo eye irritation study with europium oxide, the substance is considered to be not irritating to the eye. This result is read across to yttrium oxide, eurpium doped.
Executive summary:

In an in vivo eye irritation study, rabbits were exposed to a single dose of 0.1 g europium oxide in the left eye. The eyes of three rabbits were washed 30 seconds post application, of three rabbits the eyes were not washed. The rabbits were observed for 72 hours and scored according to Draize (1944). Based on the results, based on the MMTS, the test substance is considered to be minimally irritating to both the unwashed and washed eye. Although there was a mean total score after 72 hours (0.7), a clear decrease from 24 to 48 hours and from 48 to 72 hours was shown. Based on this study, europium oxide is not classified according to CLP Regulation (EC) No. 1272 /2008. This result is read across to yttrium oxide, eurpium doped.

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:
The rationale to read across the data is attached in section 13.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 rabbits
Time point:
24 h
Score:
13
Max. score:
110
Remarks on result:
other: Unwashed
Irritation parameter:
other: Mean total scores (unwashed)
Basis:
mean
Remarks:
of 3 rabbits
Time point:
other: at 24, 48 and at 72 hours
Score:
>= 0.7 - <= 13
Max. score:
110
Remarks on result:
other: Unwashed: 13 (24h); 3.7 (48h); 0.7 (72h)
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 rabbits
Time point:
24 h
Score:
9
Max. score:
110
Remarks on result:
other: Washed
Irritation parameter:
other: Mean total scores (washed)
Basis:
mean
Remarks:
of 3 rabbits
Time point:
other: at 24, 48 and at 72 hours
Score:
>= 0 - <= 9
Max. score:
110
Remarks on result:
other: Washed: 9 (24h); 2 (48h); 0 (72h)
Irritant / corrosive response data:
- Individual (total) scores are not available. Only the mean of the rabbits, as reported above: no further details are available.
- Yttrium oxide is considered to be mildly and minimally irritating to the unwashed and washed eye, respectively. Based on the MMTS.
Interpretation of results:
GHS criteria not met
Conclusions:
In a primary eye irritation study, 0.1 g of yttrium oxide (purity unknown) was instilled into the left eye of New Zealand Albino rabbits (6 animals). Three treated eyes were rinsed after 30 seconds. Animals were then observed for 3 days. Irritation was scored by the method of Draize (1944). In this study, yttrium oxide is slightly irritating to the eye, but not classified according to EU criteria. This eye irritation study is classified as acceptable. It does satisfy the guideline requirement for an eyes irritation study (OPPTS 870.2400) in the rabbit. This result is read across to yttrium oxide, europium doped.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No study with yttrium oxide, europium doped is available. However, several studies with yttrium oxide and also with europium oxide are present. The justification for this analogue approach is described in a report (see section 13 of IUCLID).

Skin irritation:

In an in vivo skin irritation study, 6 New Zealand Albino rabbits were dermally exposed to 0.5 g of yttrium oxide for 24 hours to ca. 2.5 cm² of one intact and one abraded skin site. Test sites were covered with an occlusive dressing for 24 hours. Animals were then observed for 3 days. Irritation was scored by the method of Draize. The primary dermal irritation index, the average of the scores of all animals and time points for erythema and oedema combined, was 0, therefore yttrium oxide is considered to be not skin irritating.

In another in vivo skin irritation study, rabbits were exposed to a single dose of 0.5 g europium oxide via occlusive application to the intact and abraded skin for 24 hours. The rabbits were observed for 72 hours and scored according to Draize. The primary dermal irritation index was 0, therefore europium oxide is considered to be not skin irritating.

Eye irritation:

In an in vivo eye irritation study, 0.1 g of yttrium oxide was instilled into the left eye of New Zealand Albino rabbits (6 animals). 3 treated eyes were rinsed after 30 seconds. Animals were then observed for 3 days. Irritation was scored by the method of Draize. The primary eye irritation index was 0 -13 (with a possible max of 110), therefore yttrium oxide is considered to be not eye irritating.

In another in vivo eye irritation study, rabbits were exposed to a single dose of 0.1 g europium oxide in the left eye. The eyes of three rabbits were washed 30 seconds post application, of three rabbits the eyes were not washed. The rabbits were observed for 72 hours and scored according to Draize. The mean scores from 24 to 72 hours were 3.3 and 3.1 respectively (out of a max of 110), not being fully reversible at 72 hours (0.7) but showing a clear decrease from 24 to 48 hours and from 48 to 72 hours. Therefore, the effect is considered reversible after 14 days and europium oxide is considered to be not eye irritating.


Justification for classification or non-classification

Based on the available studies yttrium oxide, europium doped does not have to be classified for skin and eye irritation according to CLP Regulation (EC) No. 1272 /2008 including its amendments.