Ammonium iron(III) citrate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Data is from experimental study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

The purpose of the study was to evaluate the acute dermal irritation and/or corrosive effects on skin following the application of the test article.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium iron(III) citrate

EC Number:

214-686-6

EC Name:

Ammonium iron(III) citrate

Cas Number:

1185-57-5

Molecular formula:

C6H8O7.xFe.xH3N

IUPAC Name:

Ammonium iron (III) citrate

Details on test material:

- Name of test material (IUPAC name): 2-Hydroxypropane-1,2,3-tricarboxylate, ammonium iron (3+) salt
- Common name: Ferric ammonium citrate
- Molecular formula: C6H8O7.xFe.xH3N
- Molecular weight: 264.9979 g/mol
- Smiles notation: N.[Fe+3].OC(=O)CC(O)(CC(=O)O)C(=O)O
- InChl: 1S/C6H8O7.Fe.H3N/c7-3(8)1-6(13,5(11)12)2-4(9)10;;/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);;1H3/q;+3;
- Substance type: Organic

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Conelli S.n,c., Via Milano. 61 - 28041 ARONA (Novara - Italy) and received on January 7, 1998 (shipping slip No. 00001, dated Itinerary 7. 1998).
- Age at study initiation: 2 - 3 months old
- Weight at study initiation: 2.5 - 2.8kg.
- Fasting period before study:
- Housing: housed in room T05C.
- Diet (e.g. ad libitum): The animals were fed a diet coded "2 RB 15 GLP Certificate" produced by the Charles River ltalia's feed licensec Mucedola S.r.l., Seflimo Milanese. ad libitum
- Water (e.g. ad libitum): municipal water, ad libitum
- Acclimation period: Not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C±2
- Humidity (%):50%±15
- Air changes (per hr): approximately 20 air changes per hour (filtered on HEPA 99.97%).
- Photoperiod (hrs dark / hrs light): The room was illuminated by artificial lighting with a 12-hour circadian cycle (7 a.m. - 7 p.m.).


IN-LIFE DATES: From: To: March 2- March 5, 1998

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

intact

Vehicle:

not specified

Controls:

yes

Amount / concentration applied:

0.5 ml/site

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

Observations were performed immediately and 72 hours after the 3-minute and the 1-hour exposure period in the first rabbit and at 1, 24. 48 and 72 hours after the 4-hour exposure period (all rabbits).

Number of animals:

3 female

Details on study design:

Details on study design
TEST SITE
- Area of exposure: the trunk
- % coverage: approximately 6 cm2
- Type of wrap if used: The application area was covered with a gauze patch loosely held in contact with the skin by an impermeable, non-irritant, hypoallergenic tape (occlusive patch).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual substance was removed with water
- Time after start of exposure: 1, 24. 48 and 72 hours after

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 3 minutes, 1 hour and 4 hours (for single rabbit ) and after 1, 24. 48 and 72 hours (all rabbits)

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No changes were seen at any test article application site. No clinical signs, either general or local (at the application sites), were noted in any rabbit.

Other effects:

not specified

Any other information on results incl. tables

Table 1:

Grading of Skin Reaction

1.           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 (injuries in depth)..................................................... 4                Maximum possible = 4

2.           edema Formation                No oedema......................................................................................... 0                Very slight edema (barely perceptible)................................................. 1                Slight edema (edges of area well defined by definite raising)................. 2                Moderate edema (raised approximately 1 mm...................................... 3                Severe edema (raised more than 1 mm and extending                Beyond area of exposure)....................................................................4                 Maximum possible = 4

Evaluation of results:  the dermal irritation was evaluated in conjunction with the nature and reversibility or otherwiseofthe responsesobserved.

RESULTS:

Table 2: Observation of single rabbit

Exposure period: 3 minutes

Erythema And Eschar

Obs. wade at	42F (animal No.)
3minutes	0
72 hours	0

Edema

3 minutes	0
72 hours	0

Exposure period: 1hour

ErythemaAnd Eschar

Obs. made at	42F (animal No.)
1 hour	0
72 hours	0

Edema

1 hour	0
72 hours	0

Table 3: obervation of all rabbits

Exposure period:4 hours

Erythema And Eschar

Obs. made at	42F	46F	48F
60 minutes	0	0	0
24 hours	0	0	0
48 hours	0	0	0
72 hours	0	0	0

Edema

Obs. made at	42F	46F	48F
60 minutes	0	0	0
24 hours	0	0	0
48 hours	0	0	0
72 hours	0	0	0

Applicant's summary and conclusion

Interpretation of results:

other: Not irritating

Conclusions:

Neither mortality nor adverse general clinical modifications were seen during the study. Thus, the test material was considered to be non-irritant when administrated to rabbits by dermal route.

Executive summary:

An acute dermal irritation study of test chemical was conducted in the female New Zealand White rabbit (3 animals) in accordance with EEC Guidelines (B.4) and OECD Guidelines (404).

 

0.5 ml of the test article were applied on the intact skin of the trunk to a small area (approximately 6 cm2) of skin. The application area was covered with a gauze patch loosely held in contact with the skin by an impermeable, non-irritant, hypoallergenic tape (occlusive patch).  At the end of each exposure period, residual substance was removed with water. Adjacent areas of untreated skin of each animal served as control for the test.

 

Observations were performed immediately and 72 hours after the 3-minute and the 1-hour exposure period in the first rabbit and at 1, 24. 48 and 72 hours after the 4-hour exposure period (all rabbits). Inspections for mortality and general clinical signs were made once a day.

 

No changes were seen at any test article application site. No clinical signs, either general or local (at the application sites), were noted in any rabbit. Thus, the test material was considered to be non-irritant when administrated to rabbits by dermal route.