Everzol Red CDN Crude

Endpoint summary

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

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 or test system 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	700^1			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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

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)
743^1	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.