Acetic acid, oxo-, sodium salt, reaction products with ethylenediamine and hydroxybenzenesulfonic acid monosodium salt, iron sodium salts

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2000-08-17 to 2000-08-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EC Directive No. 92/69/EEC, B.5, 31st July 1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): EDDHAS Fe, sel de K
- Molecular formula (if other than submission substance): C18H14FeN2O12S2(3K)
- Molecular weight (if other than submission substance): 687.3
- Smiles notation (if other than submission substance): O=C(O)C(NCCNC(C(=O)O)c1cc(ccc1(O))S(=O)(=O)O)c2cc(ccc2(O))S(=O)(=O)O
- InChl (if other than submission substance): InChI=1S/C18H20N2O12S2/c21-13-3-1-9(33(27,28)29)7-11(13)15(17(23)24)19-5-6-20-16(18(25)26)12-8-10(34(30,31)32)2-4-14(12)22/h1-4,7-8,15-16,19-22H,5-6H2,(H,23,24)(H,25,26)(H,27,28,29)(H,30,31,32)
- Substance type: Fe chelate
- Physical state: brownish/red powder
- Analytical purity: 55±2%
- Impurities (identity and concentrations): none
- Purity test date: 2000-10-24
- Expiration date of the lot/batch: 2001-01-24
- Stability under test conditions: at least 6 months from receipt (date of receipt: 24 July 2000)
- Storage condition of test material: at room temperature and protected from humidity
- Other:

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Age at study initiation: not reported
- Weight at study initiation: mean body weight of 3 animals 3.0 ± 0.1 kg
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): ad libitum. 110 pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ±3
- Humidity (%): 30 to 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

single application

Observation period (in vivo):

The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration of the test substance.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM:

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-comeal 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

Opacity (degree of intensity: 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
- nacrous 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

TOOL USED TO ASSESS SCORE: not reported

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

based on 3 animals

Time point:

other: mean value of the scores at each reading (24, 48 and 72h)

Score:

0

Max. score:

4

Reversibility:

other: no opacity observed

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

based on 3 animals

Time point:

other: mean value of the scores at each reading (24, 48 and 72h)

Score:

0

Max. score:

2

Reversibility:

other: no lesions observed

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

based on 3 animals

Time point:

other: mean value of the scores at each reading (24, 48 and 72h)

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: redness and discharge

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean value of the scores at each reading (24, 48 and 72h)

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean value of the scores at each reading (24, 48 and 72h)

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean value of the scores at each reading (24, 48 and 72h)

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritant / corrosive response data:

Slight conjunctival reactions were observed in all animals on day 1: a very slight or slight chemosis (grade 1 or 2), a very slight redness of the conjunctiva (grade 1) and a clear discharge were noted.
A very slight chemosis (grade 1) persisted in 2/3 animals on day 2 and in 1/3 animals on day 3. No other ocular reactions were noted during the study.
Mean scores calculated for each animal over 24, 48 and 72 hours were 0.7, 0.3 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.

Other effects:

No other effects were noted

Any other information on results incl. tables

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

Rabbit number	Region of eye	Description of ocular reactions	Scores				Mean irritation score (1)	Interpretation
			lh	24h	48h	72h
			Dl	D2	D3	D4		(-) (+)
753	Conjunctivae	Chemosis	1	1	I	0	0.7	(-)
		Redness	1	0	0	0	0.0	(-)
		Discharge	0	0	0	0	0.0
	Iris		0	0	0	0	0.0	(-)
	Corneal opacity	Intensity	0	0	0	0	0.0	(-)
		Area	0	0	0	0	0.0
	Other		*	*	*	*
	Fluorescein		/	U	/	/
769	Conjunctivae	Chemosis	2	1	0	0	0.3	(-)
		Redness	1	0	0	0	0.0	(-)
		Discharge	2	0	0	0	0.0
	Iris		0	0	0	0	0.0	(-)
	Corneal opacity	Intensity	0	0	0	0	0.0	(-)
		Area	0	0	0	0	0.0
	Other		*	*	*	*
	Fluorescein		/	U	/	/
770	Conjunctivae	Chemosis	1	0	0	0	0.0	(-)
		Redness	1	0	0	0	0.0	(-)
		Discharge	1	0	0	0	0.0
	Iris		0	0	0	0	0.0	(-)
	Corneal opacity	Intensity	0	0	0	0	0.0	(-)
		Area	0	0	0	0	0.0
	Other		*	*	*	*
	Fluorescein		/	U	/	/
(1) mean of scores on days 2, 3 and 4
h = hour
D = day
(+) = irritant according to E.E.C. criteria
(-) = non-irritant according to E.E.C. criteria
*  = None
U = Fluorescein batch No. C079
/  = Fluorescein not used

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this study, the test substance Fe3KEDDHSA is non-irritant when administered by ocular route to rabbits.

Executive summary:

The potential of the test substance Fe3KEDDHSA to induce ocular irritation was evaluated in New Zealand White rabbits according to OECD TG 405. A single dose of 100 mg of the test substance in its original form was introduced into the left conjunctival sac of three animals. The right eye was not treated and served as control. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. The interpretation of results was carried out according to the classification criteria laid down in the Regulation (EC) No. 1272/2008 (CLP).

Slight conjunctival reactions (very slight or slight chemosis, very slight redness of the conjunctiva and clear discharge) were observed in all animals on day 1 (day of application). A very slight chemosis persisted in 2/3 animals on day 2 (24 -hour reading) and in 1/3 animals on day 3 (48 -hour reading). No lesions were observed on day 3 (72 -hour reading). No other ocular reactions were noted during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.7, 0.3 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 mean scores for 2 out of 3 animals do not exceed trigger values for classification and labelling defined in the CLP. The test substance Fe3KEDDHSA is considered to be not irritating to eyes.