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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
29.04.94 to 20.07.94
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. Study not directly relevant based on the low pH of the submission substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Ferrous sulfate (FeSO4 : 7H2O = 92-96%)
- Substance type: Iron salt
- Physical state: Powder
- Analytical purity:92-96%
- Impurities (identity and concentrations): ,1% each of several other metals
- Composition of test material, percentage of components: No data
- Purity test date: 02.05.94
- Lot/batch No.: No data
- Expiration date of the lot/batch: 02-05-94
- Stability under test conditions: No data
- Storage condition of test material: Ambient temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle
- Age at study initiation:No data
- Weight at study initiation: 2.6 ±0.1kg
- Housing: Individually in polystyrene cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ±3
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 25.05.94 To: 21.06.94

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500mg
- Concentration (if solution): undiluted

Duration of treatment / exposure:
Up to four hours (3 minutes and 1 hour exposures in one animal each, and 4 hours in 3 animals)
Observation period:
Observations at 1, 24, 48  and 72 hours after removal of the dressing and then daily until day 14 in order to observe the reversibility of reactions
Number of animals:
Three
Details on study design:
TEST SITE
- Area of exposure: Flank
- % coverage: No data, area of 6cm2
- Type of wrap if used: Semi-occlusive


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test substance was removed by means of a dry compress.


SCORING SYSTEM: The interpretation of results was carried out according to the classification criteria laid down in directive 93/21/EEC Commission Directive of 27th  April 1993 adapting to technical progress for the eighteenth time Council Directive 67/548/EEC.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 hours
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 hours
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 hours
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 hours
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Very slight or well-defined cutaneous reactions were observed after application of the test substance during 3 minutes and 1 hour. Severe cutaneous
reactions were observed after application of the test substance during 4 hours. No necrosis or ulceration of the skin was observed. All lesions were reversible before the end of the 14-day observation period.
Other effects:
All overt effects fully reverible within 14 days of dose application

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a well conducted skin irritation study (according to OECD 404 and GLP), ferrous sulfate was irritating to the skin of two of three New Zealand white rabbits, and it was therefore concluded that this substance is irritating to the skin. By read-across, iron trinitrate is also assumed to be iritating to rabbit skin.

The EFSA conclusion (EFSA Journal 2012;10(1):2521; CONCLUSION ON PESTICIDE PEER REVIEW, Conclusion on the peer review of the pe sticide risk assessment of the active substance iron sulfate European Food Safety Authority) for iron sulphate irritancy was based on human data and the precautionary principle and on physical properties, and only one old reference with other citations in literature as moderate irritant without further evidence . For eye irritancy EFSA concluded Irritant (R36) (human data – precautionary, based on physical properties, only one old reference).

Aqueous solutions of iron trinitrate have low pH values, for a 5% aqueous solution of iron trinitrate nonahydrate the pH range was 1.5-2.5 and typically effective values were less than 2.0 (pH 1.5-1.7). These values would indicate potential corrosive properties for iron trinitrate and read across from iron sulphate (based on the results presented in this study summary) is not considered appropriate for assessment of iron trinitrate eye irritation but read-across does confirm the classification for skin irritation.
Executive summary:

In a skin irritation study, a single dose of 500 mg ferrous sulfate (moistened with water) was applied to the clipped skin (6cm2 on flank) of three male New Zealand white rabbits. The test substance was held in contact with the skin by means of a semi-occlusive dressing for four hours. Cutaneous reactions were recorded at 1, 24, 48 and 72 hours after removal of the dressing, and then daily until day 14 in order to observe the reversibility of the reactions. Residual test substance was removed by means of a dry compress. The mean score for erythema and oedema were recorded for each animal using 24, 48 and 72 hours values. Very slight or well-defined cutaneous reactions were observed after application of the test substance during 3 minutes and 1 hour. Severe cutaneous reactions were observed after application of the test substance during 4 hours. No necrosis or ulceration of the skin was observed. All lesions were reversible before the end of the 14-day observation period. It was concluded that ferrous sulfate was irritating to the skin. By read-across, iron trinitrate is also assumed to be iritating to rabbit skin.