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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).

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