Registration Dossier

Administrative data

Description of key information

Skin irritation

Everzol Red CDN Crude was non-irritant to skin (OECD TG404, EU Method B.4, EPA OPPTS 870.2500 and JMAFF).

                          

Eye irritation

Everzol Red CDN Crude was non-irritant to eye (OECD 405, EU Method B.5, EPA OPPTS 870.2400 and JMAFF).

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:
From January 29, 2008 to May 07, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Principles of method if other than guideline:
- Japanese Ministry of Agriculture, Forestry and Fisheries
(JMAFF), 12 Nousan, Notification No 8147, November 2000,
including the most recent partial revisions.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Harlan, Horst, The Netherlands
- Weight at study initiation: at least 1.0 kg
- Housing: individually in labeled cages with perforated floors
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 21.0 ± 3.0 °C
- Humidity (%): 30-70 %
- Photoperiod: 12hrs dark / 12hrs light
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Remarks:
Elix, Millipore S.A.S., Molsheim, France
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.5 g test article was moistened with 0.5 mL water
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
three
Details on study design:
- Area of exposure: the skin of one flank
Irritation parameter:
erythema score
Basis:
animal: 700, 727 and 730
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal: 700, 727 and 730
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation

Table 1. Individual skin irritation scores

Animal

7001

727

730

Time after exposure

Erythema

Oedema

comments

Erythema

Oedema

comments

Erythema

Oedema

comments

1 hour

0

a

0

a

0

a

24 hours

0

0

a

0

0

a

0

0

a

48 hours

0

0

a

0

0

a

0

0

a

72 hours

0

0

a

0

0

a

0

0

a

1Sentinel.

Comments:       

 No scoring possible due to red/purple staining

a  Red/purple staining of the skin by the test substance

Table 2. Mean value irritation scores

Animal

Mean 24, 48 and 72 hrs

Erythema

Oedema

700

0

0

727

0

0

730

0

0

Table 3. Animal specifications

Animal

Sex

Age at start

(weeks)

Body weight (g)

prior to application

at termination

700

8-10

1931

2067

727

7-9

1271

1360

730

7-9

1309

1429

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 404, EU Method B.4, EPA OPPTS 870.2500 and JMAFF test method test method, Everzol Red CDN Crude was non-irritant to skin. Therefore, Everzol Red CDN Crude was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the NOTOX Study Plan for 487477. Three rabbits were exposed to 0.5 g of Everzol Red CDN Crude, moistened with 0.5 mL water, by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure. No symptom of systemic toxicity were observed in the animals during the test period and no mortality occurred. All animals was no formation of erythema andoedemaon the test area within 72 hours after patch removal. On the basis of the test results given above, the response of Everzol Red CDN Crudewas categorized as non-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:
experimental study
Adequacy of study:
key study
Study period:
From February 11, 2008 to May 07, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Principles of method if other than guideline:
- Japanese Ministry of Agriculture, Forestry and Fisheries
(JMAFF), 12 Nousan, Notification No 8147, November 2000,
including the most recent partial revisions.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: at least 6weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually in labeled cages with perforated floors
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 21.0 ± 3.0 °C
- Humidity (%): 30-70%
- Photoperiod: 12-hrs dark / 12-hrs light
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 58.6 mg
Observation period (in vivo):
1, 24, 48, 72 hours and 7 days
Number of animals or in vitro replicates:
Three
Irritation parameter:
cornea opacity score
Basis:
animal: 743, 747 and 748
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: 743, 747 and 748
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: 743 and 748
Time point:
24/48/72 h
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Remarks:
Red/purple staining of the eye lids, nictitating membrane and sclera hampered scoring of erythema at 1, 24 and 48 hours after dosing.
Irritation parameter:
conjunctivae score
Basis:
animal: 747
Time point:
24/48/72 h
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Red/purple staining of the eye lids, nictitating membrane and sclera hampered scoring of erythema at 1, 24, 48 and 72 hours after dosing.
Irritation parameter:
chemosis score
Basis:
animal: 743, 747 and 748
Time point:
24/48/72 h
Score:
0.4
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 7 days
Other effects:
Red/purple staining of (peri) ocular tissues by the test
substance was observed during the observation period. This
staining hampered scoring of erythema at 1, 24, 48 and/or 72
hours after dosing. No test substance remnants were seen.

Red/purple staining of the fur on the head and paws, caused
by the test substance, was noted during the observation
period.

Table 1. Individual eye irritation scores 

Animal

Time after dosing

Cornea

Iris

Conjunctivae

Comments

Opacity

(0-4)

Area

(0-4)

Flour area

(%)2

(0-2)

Redness

(0-3)

Chemosis

(0-4)

Discharge

(0-3)

7431

1 hour

0

0

0

0

2

1

e a

24hours

0

0

0

1

1

e a

48 hours

0

0

0

0

0

e a

72 hours

0

0

0

1

0

0

e a1

7 days

0

0

0

0

0

0

e a1

747

1 hour

0

0

0

0

2

1

e a

24 hours

0

0

0

1

1

e a

48 hours

0

0

0

0

1

e a

72 hours

0

0

0

0

0

e a

7 days

0

0

0

0

0

0

e a1

748

1 hour

0

0

0

0

2

1

e a

24 hours

0

0

0

1

1

e a

48 hours

0

0

0

1

1

e a

72 hours

0

0

0

1

0

1

e a1

7 days

0

0

0

0

0

0

e a1

1Sentinel

2Green staining after fluorescein treatment (percentage of total corneal area)

 

Comments:

a   Red/purple staining of the eye lids, nictitating membrane and sclera, which hampered scoring of erythema.

a1  Red/purple staining of the eye lids, nictitating membrane and sclera, which did not hamper scoring of erythema.

e   Red/purple staining of the head and paws by the test substance.

Table 2. Mean value eye irritation scores

Animal

Mean 24, 48 and 72 hours

Corneal opacity

Iris

Conjunctive

Redness

Chemosis

743

0.0

0.0

b

0.3

747

0.0

0.0

c

0.3

748

0.0

0.0

b

0.7

Comments:

b  Red/purple staining of the eye lids, nictitating membrane and sclera hampered scoring of erythema at 1, 24 and 48 hours after dosing. Erythema grade 1 was observed at 72 hours after dosing.

c  Red/purple staining of the eye lids, nictitating membrane and sclera hampered scoring of erythema at 1, 24, 48 and 72 hours after dosing.

Table 3. Animal specifications

Animal

Sex

Age at start (weeks)

Body weight (grams)

prior to application

at termination

743

7-9

1249

1402

747

9

1625

1792

748

9

1525

1751

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405, EU Method B.5, EPA OPPTS 870.2400 and JMAFF test method, Everzol Red CDN Crude showed that non-irritant to the eye. Therefore, Everzol Red CDN was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the NOTOX Study Plan for 487478. There were no test article effects on body weight. Everzol Red CDN Crudewas given by a single ocular application at 58.6 mg amount to NZW rabbits and followed by ocular examination within 7 days. Three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The observed irritation had completely resolved within 72 hours in one animal and within 7 days in two animals. No iridial irritation or corneal opacity was observed. On the basis of the test results given above, the response of the test article was not any irritant to the eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Three rabbits were exposed to 0.5 g of Everzol Red CDN Crude, moistened with 0.5 mL water, by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours after exposure. No symptom of systemic toxicity were observed in the animals during the test period and no mortality occurred. All animals was no formation of erythema and oedema on the test area within 72 hours after patch removal. On the basis of the test results given above, the response of Everzol Red CDN Crude was categorized as non-irritant.

 

Eye irritation

Everzol Red CDN Crude was given by a single ocular application at 58.6 mg amount to NZW rabbits and followed by ocular examination within 7 days. Three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The observed irritation had completely resolved within 72 hours in one animal and within 7 days in two animals. No iridial irritation or corneal opacity was observed. On the basis of the test results given above, the response of the test article was not any irritant to the eye.

Justification for classification or non-classification