Iron digluconate

Endpoint summary

Description of key information

Iron Gluconate can be read across to D-Gluconic acid due to the comparable structures and relevant properties. D-Gluconic Acid is not a skin or eye irritant. As such Iron Gluconate is a non-irritant to skin and eye based on read-across.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

An insignificant deviation was that the drinking water analysis was performed in September as opposed to August as outlined in the study protocol

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Grimaud Freres Selection, La Corbiere, 49450 Roussay, France
- Weight at study initiation: 2 to 2.2 kg
- Housing: Individually caged in standard cages
- Diet (e.g. ad libitum): SDS/DIETEX STANRAB (P) SQC feed, ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 to 21
- Humidity (%): 45 to 65
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: adjacent non-treated surfaces served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted test substance

Duration of treatment / exposure:

Gluconic Acid was applied three times successively at a duration of three minutes, one hour, and four hours, respectively (exposure of one animal)
Gluconic Acid was applied once only, at a duration of exposure of 4 hours (exposure of two additional animals).

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Dorsum
- % coverage: Percentage not reported; covered by gauze square of 3 X 3 cm
- Type of wrap if used: Gauze square was protected by a pad consisting of a semi-occlusive micro-porous and non-allergenic dressing and held in place with a supple and aerated fastening system consisting of elastic, adhesive, hypoallergenic tape.


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

SCORING SYSTEM: in accordance with OECD guideline No. 404

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 preventing the grading of the erythema 4

Formation of oedema
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 mm) 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

ca. 0

Max. score:

4

Reversibility:

other: no erythema observed

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

ca. 0

Max. score:

4

Reversibility:

other: not applicable; no edema observed

Irritant / corrosive response data:

No dermal response to treatment was observed in any animals throughout the observation period.

Other effects:

None reported.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (EC 1278/2008)

Conclusions:

D-gluconic acid is not classified as a skin irritant

Executive summary:

D-gluconic acid is not classified as a skin irritant

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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:

2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

2 of the rabbits' body weights were less than 2 kg at study start, drinking water analysis was performed in September as opposed to August, and flurescein was used at one hour time point to examine the cornea

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Grimaud Freres Selection, La Corbiere, 49450 Roussay, France
- Weight at study initiation: 1.610 kg to 2.340 kg
- Housing: Individually housed in standard sized cages
- Diet (e.g. ad libitum): SDS/DIETEX STANRAB (P) SQC, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 to 21
- Humidity (%): 45 to 65
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted

Duration of treatment / exposure:

Single Exposure

Observation period (in vivo):

Up to 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

One dose consisting of 0.1 mL (after instillation the eyelids were held closed for one second to prevent loss of dose). Ocular changes were assessed and recorded immediately, one hour after treatment, 24 hours, 48 and 72 hours after treatment. Signs of irritation persisted in one animal and observations to day 8 were taken.

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

SCORING SYSTEM:
Ocular lesions were graded in accordance with OECD guideline No. 405

Ocular Reactions

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

Lacrimation
No lacrimation 0
Slight lacrimation (slight secretions normally present at the medial angle should not be taken into account) 1
Lacrimation with the moistening of the eyelids and of fur around eyelids 2
Lacrimation with moistening of eyelids and of fur over large areas around eye 3

Redness (refers to palpebral and bulbar conjunctiva, not to cornea and iris)
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

Iris reactions
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperamia 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

Cornea reactions*
Opacity (degrees of density, most dense area is taken for reading)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normallustre), details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

Area of cornea involved
A quarter (or less) but not zero 1
Greater than one quarter but less than half 2
Greater than half but less than three-quarters 3
Greater than three-quarters, up to whole area 4

* The zone with the most severe lesions only is described. The assessment of the area of cornea involved is described as an exponent of the
degree of opacification, on the result data sheet.

TOOL USED TO ASSESS SCORE: fluorescein
Corneal lesions seen after the instillation of fluorescein were graded using the following evaluation scale:

Grading
No epithelial damage 0
Superficial epithelial damage without loss of stromal substance (epithelial erosion) 1
Moderate ulcer with loss of stromal sustance 2
Deep ulcer (reaching Descemet0s membrane) 3
Perforating ulcer (with or without staphyloma) 4

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

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: Average 24, 48 72 hours

Score:

2.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: Average 24, 48, 72 Hours

Score:

0.67

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: Average 24, 48, 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

other: Redness

Basis:

animal #1

Time point:

other: Average 24, 48, 72 hours

Score:

2.33

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: Average 24, 48, 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

other: Redness

Basis:

animal #2

Time point:

other: Average 24, 48, 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: Average 24, 48, 72 hours

Score:

0

Max. score:

3

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: Average 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: Average 24, 48, 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

other: Redness

Basis:

animal #3

Time point:

other: Average 24, 48, 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: Average 24, 48, 72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: Average 24, 48, 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

The application of Gluconic Acid did not induce colouration of the eye and did not interfere with grading of lesions.

One hour after instillation, all animals had slight to moderate chemosis (score 1 to 2) and moderate to severe redness of the conjunctivae (score 2 to 3). Two animals also had lacrimation (score 1 to 2), lesions of iris (score 1) and one of them had corneal lesions (score 1) involving a quarter (or less) of the area (score 1).

24 hours after instillation, one animal had severe chemosis (score 3) with lacrimation (score 3) and severe redness of the conjunctivae (score 3), lesions of iris (score 1) and cornea (score 1) on an area greater than one quarter (score 2). The two other animals had slight chemosis (score 1), slight redness of conjunctivae (score 1) and one of them had also lacrimation (score 1) and lesions of iris (score 1).

48 hours after instillation, only one animal had signs, severe chemosis (score 3) with lacrimation (score 2) and severe redness of the conjunctivae (score 3), lesions of iris (score 1) and of cornea (score 2) involving a quarter (or less) of the area (score 1).

72 hours after instillation, only slight chemosis (score 1) and slight redness of the conjunctivae (score 1) persisted in Animal No. 20091235. No ocular lesion persisted in any animal at the end of the exposure period (i.e. at time 72 hours for two animals and on D8 for one animal).

Body weight of Animal Nos. 20091236 and 20091237 was slightly lower (respectively - 0.3% and - 0.4%) than their body weight, on D1. It was not considered as toxicologically relevant effect. Body weight gain of Animal No. 20091235 was normal.

Other effects:

No observations indicative of systemic toxicity or ill health were noted for any rabbits during the course of this study.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (EC 1278/2008)

Conclusions:

D-gluconic acid is not classified as an eye irritant

Executive summary:

D-gluconic acid is not classified as an eye irritant

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

Iron Gluconate did not contain any structural alerts for skin or eye irritation. The lack of alerts and the physical-chemical properties indicate that iron gluconate should not be reactive to the skin or the eye.

 

Iron Gluconate can be read across to D-Gluconic acid due to the comparable structures and relevant properties. D-Gluconic Acid is not a skin or eye irritant. As such Iron Gluconate is considered to be a non-irritant to skin and eye based on read-across.

Read across justification summaries for skin and eye irritation are attached to the end point summary