REAKTIV-GELB F-68 072 FW

Endpoint summary

Description of key information

The test substance is not skin irritating, but slightly irritating to eyes

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:

06 April 1993 to 09 April 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test species: New Zealand albino rabbit
Strain: Chbb: NZW (SPF)
Origin: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 7950 Biberach
Number of animals: 3
Animal identification: numbered ear tags
Animal weights: 2.8 - 3.0 kg
Age of animals: about 3 - 5 months
Animal housing: in fully air-conditioned rooms, separate cages (arranged in a battery)
Ambient temperature: 18 ± 3 °C
Relative humidity: 55 ± 20 %
Lighting time: 12 hours per day
Diet: Altromin 2123 maintenance diet - rabbits (Altromin GmbH, Lage/Lippe), ad libitum and hay (approx. 15 g daily)
Drinking water: deionised, chlorinated water from automatic water dispensers, ad libitum

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

yes, concurrent no treatment

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

About 24 hours before the start of the study the hair in the dorsal region of the body of 3 rabbits was removed with an electric clipper over an area of about 25 cm2. Only animals with intact skin were used.

Each animal was treated with 0.5 g Reaktiv-Gelb F-68 072 FW pasted with 0.25 ml isotonic saline. The substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster (specially produced by Beiers-dorf AG, Hamburg). The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.

The exposure period was 4 hours. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water.

Examinations of the skin took place after 30 - 60 minutes, and 24, 48 and 72 hours after removal of the patches.

Erythema, eschar formation and oedema were evaluated numerically according to the technique of DRAIZE.

Irritation parameter:

edema score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

30 - 60 minutes after removal of the patches all animals showed very slight erythema and two animals very slight oedema. One day after removal of the patches two animals showed a very slight or a well defined erythema. Two days after removal of the patches a very slight erythema was observed in one animal. Three day after removal of the patches all irritations were reversible.

DRAIZE SKIN TEST RESULTS

ANIMAL NUMBER	ERYTHEMA				MEAN SCORE	OEDEMA				MEAN SCORE
	Time after decontamination					Time after decontamination
	30-60 MIN	1 DAY	2 DAYS	3 DAYS		30-60 MIN	1 DAY	2 DAYS	3 DAYS
95	1	1	0	0	0.3	1	0	0	0	0.0
96	1	2	1	0	1.0	1	0	0	0	0.0
97	1	0	0	0	0.0	0	0	0	0	0.0
	OVERALL MEAN : 0.4					OVERALL MEAN: 0.0

The means have been calculated using the day 1,2 & 3 values

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study Reaktiv-Gelb F-68 072 FW is not irritating to skin.

Executive summary:

Testing for primary dermal irritation provides information on the irritant effect of the test substance on the skin following a single dermal application and serves as a basis for classification and labelling.

 

The present study was conducted in compliance within EEC Directive B.4. 'Acute toxicity Skin Irritation' of the Directive 84/449/EEC and OECD Guidelines for Testing of Chemicals, 404 "Acute Dermal Irritation/Corrosion". This study was conducted in compliance with the Principles of Good Laboratory Practice(GLP).

 

Testing of Reaktiv-GelbF-68 072FW for primary dermal irritation in the rabbit showed, that the substance is not irritating to skin.

 

30 - 60 minutes after removal of the patches all animals showed very slight erythema and two animals very slight oedema. One day after removal of the patches two animals showed a very slight or a well defined erythema. Two days after removal of the patches a very slight erythema was observed in one animal. Three day after removal of the patches all irritations were reversible.

 

Based on the results of this study Reaktiv-GelbF-68072FW is not irritating to skin.

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:

27 April 1993 to 25 May 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test species: New Zealand albino rabbit
Strain: Chbb: NZW (SPF)
Origin: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 7950 Biberach
Number of animals: 3
Animal identification: numbered ear tags
Animal weights: 3.8 - 3.9 kg
Age of animals: about 3 - 5 months
Animal housing: in fully air-conditioned rooms, separate cages (arranged in a battery)
Ambient temperature: 18 ± 3 °C
Relative humidity: 55 ± 20 %
Lighting time: 12 hours per day
Diet: Altromin 2123 maintenance diet - rabbits (Altromin GmbH, Lage/Lippe), ad 1ibitum and hay (approx. 15 g daily)
Drinking water: deionised, chlorinated water from automatic water dispensers, ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

Exposure 24 hours

Observation period (in vivo):

72 hours - Effects were still present in the eyes after 72 hours, further examinations were carried out after 7 days.

Number of animals or in vitro replicates:

3

Details on study design:

About 24 hours before the start of the study the test eyes of all animals were examined under UV light for corneal lesions after instillation of one drop of a 0.01 % fluorescein-sodium solution. Only animals without ocular abnormalities were used for the study.

100 mg Reaktiv-Gelb F-68 072 FW was applied once to the conjunctival sac of the left eye of 3 rabbits. The untreated eyes served in each case as a control.

24 hours after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein-sodium solution took place, the treated eyes were washed out thoroughly with physiological saline at approx. 37 °C.

The eyes were examined 1, 24, 48 and 72 hours after application of the test substance. At 24 and 72 hours as well as after 7 days, the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded. Since effects were still present in the eyes after 72 hours, further examinations were carried out after 7 days.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

One hour up to three days p.a. the conjunctivae of all animals showed deeper crimson red up to diffuse beefy red as well as slight swellings up to obvious swellings in two animals. One hour up to one day slight swellings up to obvious swellings were noted in one animal. Additionally clear, from substance discoloured discharge as well as white viscous discharge and bleeding at the nictating membrane were observed. 7 days p.a. all irritations were reversible.

RABBIT EYE IRRITATION TEST - READINGS

ANIMAL NUMBER	SEX	EYE USED	INIT PAIN REACTION	IRRIGAT’N	ELAPSED TIME	CORNEA		IRIS	CONJUNCTIVA
						OPACITY	AREA		REDNESS	CHEMOSIS	DISCHARGE
66	F	LEFT	NONE	24 HRS	1.2 HRS	0	0	0	3	2	2
					1 DAY	0	0	0	3	2	1
					2 DAYS	0	0	0	2	1	0
					3 DAYS	0	0	0	2	1	0
					7 DAYS	0	0	0	0	0	0
68	F	LEFT	VERY SEVERE	24 HRS	1.1 HRS	0	0	0	2	2	2
					1 DAY	0	0	0	3	1	0
					2 DAYS	0	0	0	2	0	0
					3 DAYS	0	0	0	2	0	0
					7 DAYS	0	0	0	0	0	0
72	F	LEFT	NONE	24 HRS	1.2 DAYS	0	0	0	3	2	2
					1 DAY	0	0	0	3	1	0
					2 DAYS	0	0	0	2	1	0
					3 DAYS	0	0	0	2	1	0
					7 DAYS	0	0	0	0	0	0

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Testing of Reaktiv-Gelb F-68 072 FW for primary eye irritation in the rabbit showed, that the substance is slightly irritating to eyes.

Executive summary:

Testing for primary irritation in the rabbit eye provides information on ocular lesions after a single application of the test substance to the conjunctival sac of the eye and serves as a basis for classification and labelling.

 

The present study was conducted in compliance with EEC Directive B.5. 'Acute toxicity Eye Irritation' of the Directive 84/449/EEC and OECD Guidelines for Testing of Chemicals, 405 "Acute Eye Irritation/Corrosion". This study was conducted in compliance with the Principles of Good Laboratory Practice (GLP).

 

One hour up to three days p.a. the conjunctivae of all animals showed deeper crimson red up to diffuse beefy red as well as slight swellings up to obvious swellings in two animals. One hour up to one day slight swellings up to obvious swellings were noted in one animal. Additionally clear, from substance discoloured discharge as well as white viscous discharge and bleddings at the nictating membran were observed.

 

7 days p.a. all irritations were reversible.

 

Testing of Reaktiv-Gelb F-68 072 FW for primary eye irritation in the rabbit showed, that the substance is slight irritating to eye. The substance is classified under CLP as "Eye Irritant, Cat 2", but does not fulfil the criteria for eye irritation under the Dangerous Substances Directive.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / Corrosion.

A single study was evaluated on this endpoint. In these the substance was tested for primary dermal irritation and corrosiveness. Very slight oedema and erythema became apparent within the observation period of 72 hours, however these symptoms were fully reversible within 3 days. Signs of toxicity were not observed. This evidence indicates no hazard potential to the skin and the test substance may therefore be regarded as 'not irritating to the skin’. It is not a dermal corrosive. No risk phrase or classification is required.

 

Eye irritation.

 A single study was evaluated on this endpoint. In these the substance was tested for acute irritation and was found to be slightly irritating to the rabbit eye. Effects to the conjunctivae (redness) were noted in all animals assessed leading to a mean overall score on the Draize scale of 2.3; however these were fully reversible within 7 days. The result of the overall mean score for all 3 animals triggers the classification “Irritating to eyes” Category 2, H319: Causes serious eye irritation under CLP.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP an in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

 

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC), but did trigger classification under the CLP Regulation (EC No 1272/2008). Classification for irritation effects is therefore Category 2 “Irritating to eyes”.