Ammonium iron(III) trimethylenediaminetetraacetate hemihydrate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 April 1991 - 11 April 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was peformed according to OECD guidelines and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium iron(III) trimethylenediaminetetraacetate hemihydrate

EC Number:

400-660-3

EC Name:

Ammonium iron(III) trimethylenediaminetetraacetate hemihydrate

Cas Number:

111687-36-6

Molecular formula:

Hill formula: C11 H18 Fe N3 O8 CAS formula: C11 H14 Fe N2 O8.H4N

IUPAC Name:

iron(3+) ammonium 2-({3-[bis(carboxylatomethyl)amino]propyl}(carboxylatomethyl)amino)acetate hydrate

Details on test material:

Name: 1,3-Propylenediaminetetraacetic acid, ferric-ammonium complex (PDTA-FeNH4)
Appearance: fine yellow crystalline powder,
Batch No.: GW-1000

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex, England.
- Age at study initiation: Young
- Weight at study initiation: 2.77 - 2.80 kg
- Housing: The rabbits were housed individually in suspended stainless steel cages (Type RCI0/l) mounted in mobile batteries (Modular Systems and Development Company Limited, london, England). The cages measured 61 x 76 x 46 cm high and were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent crepe paper which was changed regularly.
- Diet (e.g. ad libitum): Animals had free access to food hoppers containing pelleted diet, (S.Q.C. Rabbit Diet - Special Diet Services limited, Witham, Essex, England).
- Water (e.g. ad libitum): The rabbits had free access to tap water supplied to each cage by an automatic piped system
- Acclimation period: three or four weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-19
- Humidity (%): 39-56
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 2 April 1991 - 11 April 1991

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as the control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

The behaviour of each rabbit was observed for several minutes immediately following instillation of the test material to allow
assessment of the initial pain response.
The animals were returned to their cages and checked at least twice during the first hour after dosing and at regular intervals
throughout the day to ensure no severe injury passed un-noticed. Ocular reactions to treatment were assessed one hour, 24, 48 and 72 hours after treatment.

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not applicable

SCORING SYSTEM:
Scoring system eye irritation

Cornea: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacrous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Area of Cornea Involved
1 One quarter (or less) but not zero
2 Greater than one quarter but less than half
3 Greater than half but less than three quarters
4 Greater than three quarters, up to whole area

Iris
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

0 Blood vessels normal
1 Some blood vessels definitely hyperaemic
(injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)
0 No swelling 0
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

Discharge
0 No discharge
1 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 Discharge with moistening of the lids and hairs just adjacent to lids
3 Discharge with moistening of the lids and hairs a considerable area around the eye

TOOL USED TO ASSESS SCORE: An ophthalmoscope was used to facilitate inspection of the eyes

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No effects observed

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0

Max. score:

2

Remarks on result:

other: No effects observed

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Slight injection of the conjunctival blood vessels or a diffuse crimson-red appearance to the conjunctiva was observed in all animals one hour after instillation of 0.1 g PDTA-FeNH4. Slight injection persisted in one animal during the following 48 hours.

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No effects observed

Irritant / corrosive response data:

Slight injection of the conjunctival blood vessels or a diffuse crimson-red appearance to the conjunctiva was observed in all animals one hour after instillation of 0.1 g PDTA-FeNH4. Slight injection persisted in one animal during the following 48 hours. The eyes of all rabbits were overtly normal at the 72 hour examination. Instillation of the test material caused a very slight or slight initial pain response.

Any other information on results incl. tables

Irritation responses

Rabbit No and sex	Region of the eye		Hours after instillation					Average 24-48-72 hours
			1	24	48	72	4-7(days)
1-m	Cornea	Degree of opacity	0	0	0	0	-	0
		Area	0	0	0	0	-	0
	Iris		0	0	0	0	-	0
	Conjunctivae	Redness	2	0	0	0	-	0
		Chemosis	0	0	0	0	-	0
		Discharge	0	0	0	0	-	0
2-m	Cornea	Degree of opacity	0	0	0	0	-	0
		Area	0	0	0	0	-	0
	Iris		0	0	0	0	-	0
	Conjunctivae	Redness	0	1	0	0	-	0.33
		Chemosis	0	0	0	0	-	0
		Discharge	0	0	0	0	-	0
3-m	Cornea	Degree of opacity	0	0	0	0	-	0
		Area	0	0	0	0	-	0
	Iris		0	0	0	0	-	0
	Conjunctivae	Redness	1	1	1	0	-	0.67
		Chemosis	0	0	0	0	-	0
		Discharge	0	0	0	0	-	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Not irritating to the eye.

Executive summary:

The potential of 1,3-Propylenediaminetetraacetic acid, ferric-ammonium complex, hereafter referred to as PDTA-FeNH4, to cause damage to the conjunctiva, iris or cornea was assessed in three New Zealand White rabbits, each subject to single ocular instillation of 0.1 g of the test material. Ocular reactions were examined 1, 24, 48 and 72 hours after treatment. Slight injection of the conjunctival blood vessels or a diffuse crimson-red appearance to the conjunctiva was observed in all animals one hour after instillation. Slight injection persisted in one an irna1 duri ng the following 48 hours. The eyes of all rabbits were overtly normal at the 72 hour examination. Instillation of the test material caused little initial pain response.