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

Endpoint summary

Description of key information

Four acute skin irritation/corrosion studies and four eye irritation studies were performed in rabbits generally according to the OECD Guideline No. 404. Application of EDDHMA-Fe to the rabbit skin or eye was evaluated as not irritating in all four studies.
Four eye irritation studies, performed according to OECD Guideleine 405 with the test item FeNaEDDHA in rabbits, showed that the test substance does not cause eye irritation. Application of EDDHMA-FeNa/K to the rabbit eye was evaluated as not irritating in all four studies. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 1987 - May 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Relatively well reported study; 3 days of observation instead of 14 days.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Principles of method if other than guideline:

- sex of rabbits is unknown
- no initial and confirmatory test

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rosemead Rabbits, Waltham Abbey, Essex, England
- Age at study initiation: 3 months old
- Weight at study initiation: 2.76 - 2.89 kg
- Housing: individually housed in suspended stainless steel cages
- Diet (e.g. ad libitum): free access (to S.Q.C. Rabbit Diet, Special Diet Services Limited, Witham, Essex, England)
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: at least 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 (range 15 - 23)
- Humidity (%): 55 (range 40 - 70)
- Air changes (per hr): 15 complete air changes per hour without re-circulation
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light per day


IN-LIFE DATES: From: April 28, 1987 To: May 1, 1987

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

other: moistened with 0.2 ml distilled water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): not applicable (moistened with 0.2 ml distilled water

Duration of treatment / exposure:

4 hours

Observation period:

3 days (1 hour, 24, 48 and 72 hours after patch removal)

Number of animals:

3 rabbits

Details on study design:

TEST SITE
- Area of exposure: gauze patch was 3 x 2 cm
- % coverage: no info
- Type of wrap if used: The rabbit was securely restrained by a technician. Two test sites (6 x 6 cm) were marked on either side of the clipped area of dorsum and moistened by direct application of 0.2 ml distilled water per test site. A single dose (0.5 g) was impregnated onto an unmedicated gauze patch (3 x 2 cm) and was held in place on the left test site by strips of Blenderm (3-M Company). The right test site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated. Pads of cotton wool and elasticated bandage were used to protect the patches and ensure good contact between the skin and the test material during the four-hour exposure period.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressings were removed after four hours exposure. Where necessary, the treatment sites were gently washed with warm water and dried with paper towels to remove excessive amounts of test material adhering to the skin.
- Time after start of exposure: 4 hours


SCORING SYSTEM: see below

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24/48/72 h after patch removal

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24/48/72 h after patch removal

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

No other dermal irritation response was observed in any animal.

Other effects:

No.

Summary of dermal lesions on clipped and intact skin (following 4-h application).

no.	Effect	Hour	Days after application						Mean score erythema 24/48/72 h	Mean score oedema 24/48/72 h
		1	1	2	3	7	14
523M	Erythema/ eschar Oedema	0 0	0 0	0 0	0 0	- -	- -		0	0
524M	Erythema/ eschar Oedema	1 0	0 0	0 0	0 0	- -	- -		0	0
525M	Erythema/ eschar Oedema	0 0	0 0	0 0	0 0	- -	- -		0	0
Mean Group									0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based on the results of the present study, it was concluded that Bolikel FE induced practically no skin irritation, so the test material is classified as non-irritant to the skin. Reversibility of the slight skin effect in one animal occurs.

Executive summary:

A primary dermal irritation study was conducted on three male white rabbits using test substance Bolikel FE. The method is equivalent to OECD Guideline 404 (acute Dermal Irritation/Corrosion). The study is designed and performed according to Good Laboratory Practice Standards.

Each animal received 0.5 g test material. A single 4 -hour, semi-occluded application of the test material to the intact skin produced immediately after patch removal very slight erythema at the test site of one animal. This effect disappeared after 24 hours after patch removal. Necrosis and ulceration were not reported.

Based on the results of the present study, it was concluded that Bolikel FE induced practically no skin irritation, so the test material is classified as non-irritant to the skin. Reversibility of the slight skin effect in one animal occurs.

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:

experimental study

Adequacy of study:

key study

Study period:

May 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Relatively well reported study. Observation period 8 days instead of 21 days.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

observation period of 8 days instead of 21 days; sex unknown

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Froxfield S.P.F. Rabbits, Broadway Farm, Froxfield, Hampshire, England
- Age at study initiation: at least 3 months old
- Weight on arrival: 2.29-2.38 kg
- Weight at study initiation: 3.08-3.67 kg
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): free access (to S.Q.C. Rabbit Diet, Special Diet Services Limited, Witham, Essex, England)
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 (range 15 - 23)
- Humidity (%): 55 (range 40 - 70)
- Air changes (per hr): 15 complete air changes per hour without re-circulation
- Photoperiod (hrs dark / hrs light): 12 hours artificial light per day


IN-LIFE DATES: From: May 11, 1987 To: May 19, 1987

Vehicle:

unchanged (no vehicle)

Controls:

other: other eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g test material
- Concentration (if solution): not applicable

Duration of treatment / exposure:

Single application (the eyelids were gently held together for one second and then released. The left eye remained untreated).

Observation period (in vivo):

8 days (1 hour, 24, 48 and 72 hours and on Day 8)

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

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

SCORING SYSTEM: see below (additionally an assessment was made for the pain response)

TOOL USED TO ASSESS SCORE: ophthalmoscope and fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24/48/72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24/48/72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24/48/72 hours

Score:

1.78

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24/48/72 hours

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritant / corrosive response data:

No

Other effects:

No

Summary of ocular lesions

Anim. No.	Effect	Hours	Days after application					Mean score cornea Days 1/2/3	Mean score iritis Days 1/2/3	Mean score redness Days 1/2/3	Mean score chemosis Days 1/2/3
		1	1	2	3	8	14
504M	Cornea Iris Redness Chemosis	2 1 1 1	0 1 2 0	0 0 2 1	0 0 1 0	0 0 0 0	- - - -	0	0.33	1.67	0.33
511M	Cornea Iris Redness Chemosis	0 1 2 0	0 0 2 0	0 0 2 0	0 0 1 0	0 0 0 0	- - - -	0	0	1.67	0
512M	Cornea Iris Redness Chemosis	0 1 2 1	0 1 2 1	0 1 2 0	0 0 2 0	0 0 0 0	- - - -	0	0.67	2	0.33
Mean all anim.								0	0.33	1.78	0.22

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based on the results of the present study, it was concluded that the test compound, Bolikel FE, induced a reversible very slight eye irritation. So the test material was a ‘non-irritant’ to the eye and therefore not classifiable according to OECD-GHS.

Executive summary:

A study was conducted to assess the irritancy potential of Bolikel FE to the eye of three New Zealand Albino rabbits. The study was performed according to OECD Guideline 405 (Acute Eye Irritation/Corrosion) and also according to Good Laboratory Practice Standards.

A single application of 0.1 g of the test material to the right eye of the rabbit produced redness of the conjunctivae, slight chemosis and iridial congestion were observed amongst all three animals during the first 24 hours. Translucency of up to one-quarter of the cornea was also apparent in one rabbit at the one hour examination. Only injection of the conjunctival blood vessels was observed at the 72-hour examination and all ocular lesions had resolved by Day 8.

Based on the results of the present study, it was concluded that the test compound, Bolikel FE, induced a reversible very slight eye irritation. So the test material was a ‘non-irritant’ to the eye and therefore not classifiable according to OECD-GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Four acute skin irritation/corrosion studies in albino rabbits were performed to determine the irritant or corrosive potency of the test substance EDDHMA-Fe on the albino rat skin.These tests were generally based on the OECD Guideline 404 (Acute Dermal Irritation/Corrosion) and were performed on 3 -6 rabbits, checked for normal skin conditions. The studies showed that EDDHMA-Fe does not cause skin irritation.

Eye irritation

Four eye irritation studies were performed according to the OECD Guideline 405 (Acute Eye Irritation/Corrosion) with the test item EDDHMA-Fe. The test was performed on 3 -6 rabbits. An amount of 0.1 g (three studies) or 37 mg (corresponding to a volume of 0.1 mL (one study)) of the test item was placed into the conjunctival sac of one of the eyes of each animal; the other eye served as control. The animals were checked daily for systemic symptoms and mortality. The studies showed that the test substance does not cause eye irritation as none of the animals achieved a mean score leading to classification according to GHS.

Justification for selection of skin irritation / corrosion endpoint:
One key (GLP) study and three supporting studies (two GLP studies and one older study)

Justification for selection of eye irritation endpoint:
One key (GLP) study and three supporting studies (two GLP studies and one older study)

Justification for classification or non-classification

Based on the results of four eye irritation studies and four skin irritation studies the test substance EDDHMA-Fe is not classified and labelled as an eye or skin irritant according to Regulation 1272/2008/EC (CLP).