Neodymium di(2-ethylhexyl) phosphate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1 September 2006 to 20 April 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: the study was performed according to internationally recognised guidelines and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

the temperature and relative humidity sometimes outside of the target ranges (this minor deviation was not considered to have compromised the validity or integrity of the study)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

see higher

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

see higher

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation: on the day of treatment, the animals were 2 to 4 months old
- Weight at study initiation: on the day of treatment, the animals had a mean body weight of 3.0 ± 0.2 kg
- Housing: individually in Pajon cages (50 cm x 57 cm x 75 cm)
- Diet: free access to 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France)
- Water: drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Humidity: 30 to 70%
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12hrs dark / 12hrs light)

IN-LIFE DATES: from 19 September 2006 (day of treatment of the first animal) to 24 September 2006 (end of the observation period)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount: 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 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 24 h

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicale

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 24 h

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

A slight chemosis (grade 1) was observed in all the animals on days 1.
A slight redness of the conjunctiva (grade 1) was noted in all the animals at 1 hours after treatment; it persisted at time point 24 hours in 2/3 animals.
No other ocular reactions were recorded during the study.

Other effects:

Residual test item was noted in all the animals on day 1 only.

Any other information on results incl. tables

Table 1: Individual ocular examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)

 

Rabbit number	Region of the eye	Description of ocular reactions	Scores				Mean irritation score (1)	Interpretation (+) or (-)
			1h	24h	48h	72h
646	Conjunctivae	Chemosis Redness Discharge	1 1 0	1 0 0	0 0 0	0 0 0	0.3 0.0 0.0	(-) (-)
	Iris		0	0	0	0	0.0	(-)
	Corneal opacity	Intensity Area	0 0	0 0	0 0	0 0	0.0 0.0	(-)
	Other		Su	*	*	*
	Fluorescein		/	U	/	/
608	Conjunctivae	Chemosis Redness Discharge	1 1 0	1 1 0	0 0 0	0 0 0	0.3 0.3	(-) (-)
	Iris		0	0	0	0	0.0	(-)
	Corneal opacity	Intensity Area	0 0	0 0	0 0	0 0	0.0 0.0	(-)
	Other		Su	*	*	*
	Fluorescein		/	U	/	/
609	Conjunctivae	Chemosis Redness Discharge	1 1 0	1 1 0	0 0 0	0 0 0	0.3 0.3	(-) (-)
	Iris		0	0	0	0	0.0	(-)
	Corneal opacity	Intensity Area	0 0	0 0	0 0	0 0	0.0 0.0	(-)
	Other		Su	*	*	*
	Fluorescein		/	U	/	/

(1) mean of scores on days 2, 3 and 4

(+) = irritant according to E.E.C. criteria

(-) = non-irritant according to E.E.C. criteria

* = none

Su = residual test item

U = fluorescein batch No. K 742

/ = fluorescein not used

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Neodymium tris(di-2-ethylhexylphosphate) is not considered to be an eye irritant in the rabbit according to EU criteria.

Executive summary:

In a primary eye irritation study performed according to OECD 405, EC B.5 ,US/EPA/OPPTS 870.2400 and GLP (CIT report No.32231 TAL, 2007), scored as validity 1 according to Klimisch criteria, 100 mg of neodymium tris(di-2-ethylhexylphosphate) were instilled into the conjunctival sac of the left eye of 3 male New Zealand White rabbits. Exposed eyes were not rinsed. 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.

A slight chemosis was observed in all the animals on days 1,  from 1 hour up to 24 hours after treatemnt.

A slight redness of the conjunctiva was noted in all the animals 1h after treatement; it persisted up to 24 hours in 2/3 animals.

Residual test item was noted in all the animals on day 1 only.

No other ocular reactions were recorded during the study.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.3, 0.3 and 0.3 for chemosis, 0.0, 0.3 and 0.3 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.

 

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 international guideline requirements for acute eye irritation or corrosion.