2-Propanone, reaction products with diphenylamine

Endpoint summary

Description of key information

Eye and skin irritation studies that were conducted on albino rabbits concluded that the test article is not irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 August 1983 to 12 August 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to GLP reguations of the FDA effective 20/06/1979.

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.41

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Six healthy albino rabbits were selected for this test from a larger group which had been quarantined at least one week. The animals were received from Nichol as Helf on 23/07/1983 and 30/07/1983.
Animals were identified by cage notation and with a uniquely numbered metal ear tag. The animals were housed 2 per cage in suspended wire mesh cages. Bedding was placed beneath the cages. Fresh Purina Rabbit Chow (Diet #53-21) and water were freely available.
The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled and kept clean and vermin free.

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other: Mazola oil

Controls:

no

Amount / concentration applied:

Six healthy albino rabbits were dosed dermally with Aminox CN 5731 0.5 g of the test article was applied to 1 intact and 1 abraded site on the clipped back for a total dose of 1.0 g/rabbit

Duration of treatment / exposure:

Exposure time: 72 hours

Observation period:

The skin reactions were observed 24 and 72 hours after dosing.

Number of animals:

Six

Details on study design:

Preparation of test site
Prior to application of the test article, the back and sides of each animal were clipped free of hair. The left side of each animal was abraded with a bent tip needle. Three abrasions, approximately 2-3 cm apart, extending the length of the exposure site were made. The abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to produce bleeding. The right side of wach animal remained intact.

Experimental design
The test article was applied to two areas, 1 intact and 1 abraded, on the prepared site, on the back of each of the six rabbits. Test substance was applied as 50% weight/volume mixture in a suitable vehicle and dosed by dry weight. 0.5 g/site for a total dose volume of 1.0 g/rabbit. Test article was covered with 2.5 cm square gauze patches which were secured with adhesive tape. The torso was wrapped with plastic which was secured with adhesive tape. The sites were occluded for 24 hours at which time the patches were removed.

Type and frequency of observations
Animals observed for skin reactions at 24 and 72 hours after application of the test article. Erythema and edema were scored according to the numerical Draize technique. Additional signs and general health of the animals was monitored at each observation time.

Analysis of data
The Primary Irritation Index was calculated by adding the mean values (6 rabbits) for erythema/eschar and edema on intact and abraded skin at 24 and 72 hours (a total of 8 values) and dividing the sum by 4.
A primary irritant is defined as a substance which is not corrosive but which results in an empirical score of 5 of more.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Erythema was minimal at 24 hours and was absent to slight at 72 hours. No odema was observed.

Other effects:

None specified.

 Individual scores

	Rabbit Number						Mean score
	A9707	A9774	A9775	A9777	A9778	A9779
Erythema & Eschar Formation
Intact skin – 24 hours	1^a	0^a	0^a	1^a	1^a	1^a	0.67
Intact skin – 72 hours	2^a	0^a	1^a	1^a	1^a	1^a	1.00
Abraded skin – 24 hours	1^a	0^a	0^a	1^a	1^a	1^a	0.67
Abraded skin – 72 hours	2^a	1^a	1^a	1^a	1^a	1^a	1.17
Edema
Intact skin – 24 hours	0	0	0	0	0	0	0
Intact skin – 72 hours	0	0	0	0	0	0	0
Abraded skin – 24 hours	0	0	0	0	0	0	0
Abraded skin – 72 hours	0	0	0	0	0	0	0
				Sum of mean scores =			3.51
	PRIMARY IRRITATION INDEX = SUM OF MEAN SCORES/4=						0.88

Key:

a = test article remaining on treated site

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: 16 CFR 1500.3(c)(4)

Conclusions:

The Primary Irritation Index is 0.88. Therefore, the test article is a non-irritant as defined in 16 CFR 1500.3(c)(4).

Executive summary:

The objective of the study was to determine the dermal irritation potential of Aminoz CN 5731. Study was conducted in accordance to GLP and test guidline 16 CFR 1500.41. Results of the study concluded that the mean primary irritation idex is 0.88 for the test article. Erythema was minimal at 24 hours and was absent to slight at 72 hours. No odema was observed. Therefore to conclude, the test article is classified as a not irritating under 16 CFR 1500.3(c)(4)

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Detailed study, not in accordance to GLP or recognised test guidlines.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

None specified

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 g of the test article was applied to intact and abraded skin (1.0g total applied to each rabbit)

Duration of treatment / exposure:

Exposure time: 72 hours

Observation period:

Observations conducted 24 hours and 72 hours after application

Number of animals:

12 rabbits (6 rabbits treated on intact skin and 6 rabbits treated on abraded skin)

Details on study design:

Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits.
Twelve healthy adult New Zealand White Albino rabbits are used for 1 – 4 test substances. Twenty four hours prior to applying the materials, the hair is removed from the backs of the animals with electric clippers in such a way as to avoid abrasions.

An amount of 0.5 mL (in case of liquids) or 0.5 g (in case of solids or semi-solids) of the test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbit is wrapped with an impervious material to maintain test patches in position and to retard evaporation of volatile substances.
Six rabbits are treated on the intact skin, the other six on the abraded skin. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.

After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize (J. Pharmacol. 82 (1944) 377 – 390). A second reading is made 48 hours later (72 hours after application).

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Score:

0.2

Reversibility:

no data

Remarks on result:

other: Abraded skin

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Score:

0

Reversibility:

other: No skin reactions observed

Remarks on result:

other: Intact skin

Irritant / corrosive response data:

At the end of the 24-hour application one rabbit treated on the abraded skin showed very slight erythema. After 72 hours another rabbit treated on the abraded skin showed very slight scaliness. No skin reactions were observed in rabbits treated on the intact skin.

Other effects:

None

Individual and average skin irritation score of the product WTR 9a Permanax

	Intact skin			Abraded skin
Rabbit No.	24 hours A	24 hours B	72 hours	Rabbit No.	24 hours A	24 hours B	72 hours
6580	0	0	0	6574	0	0	0
6581	0	0	0	6575	0	0	1
6582	0	0	0	6576	0	0	0
6583	0	0	0	6577	0	0	0
6584	0	0	0	6578	1	0	0
6585	0	0	0	6578	0	0	0
Average	0		0	Average	0.2		0.2

 

A = erythema

B = Edema

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: Draize (J. Pharmacol. 82 (1944) 377 - 390) and CIVO-grading system

Conclusions:

WTR 9a compound caused very slight skin irritation in two out of twelve rabbits. After 72 hours another rabbit treated on the abraded skin showed very slight scaliness. No skin reactions were observed in rabbits treated on the intact skin. Therefore it can be concluded that the test article is not a skin irritant.

Executive summary:

The aim of the study was to determine the irritancy potential of WTR 9a compound using the pacth-test technique and evaluating the results using the Draize method of evaluation and CIVO-grading system. The WTR 9a compound caused one rabbit showed very slight erythema after 24 hours of the application on abraded skin another rabbit showed very slight scaliness after 72 hours. No skin reactions were observed in rabbits treated on intact skin however. Therefore it can be concluded that WTR 9a compound is not a skin irritant.

Reference 3

Endpoint:

skin irritation / corrosion

Remarks:

no data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study not conducted in accordance to GLP or any recognised test guidelines

Qualifier:

no guideline available

GLP compliance:

no

Remarks:

Predates GLP

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

Not specified

Type of coverage:

other: Intradermal injection

Preparation of test site:

not specified

Vehicle:

other: Olive oil (U.S.P)

Controls:

yes

Amount / concentration applied:

0.5 cc

Duration of treatment / exposure:

24 hours

Observation period:

Observations conducted 24 hours after exposure

Number of animals:

Three

Details on study design:

Samples of Aminox A-3250 dissolved in Olive Oil (U.S.P.) in 5% amounts, and 0.5cc aliquots of these solutions were injected intradermally under aseptic conditions.

Plain Olive Oil (U.S.P.) serveed as a control, and was test in a similar manner in one animal.

Observations were made 24 hours after the intradermal injection.

Irritant / corrosive response data:

None specified

Other effects:

None specified

Sample	Rabbit #	Reaction on skin
	4	+
	5	+
	6	+
Control	7	+

Legend:

-          No irritation

+     Slight reaction

++   Defined reaction

+++   Very definitive reaction

++++ Very definite and reading reaction

Interpretation of results:

other: Slight reaction

Remarks:

Criteria used for interpretation of results: not specified

Conclusions:

Under the conditions of the study Aminox was shown to induce a slight reaction when injected intradermally into rabbits.

Executive summary:

Under the conditions of the study Aminox was shown to induce a slight reaction when injected intradermally into rabbits.

Reference 4

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 August 1983 - 4 August 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to GLP reguations of the FDA effective 20/06/1979.

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.42.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Six healthy albino rabbits, free from evidence of ocular irritation, were selected for this test from a larger group which had been quarantined at least one week. The animals were received from Ace Animals 28/06/1983, 04/07/198 and 19/07/1983.
The animals were identified by cage notation and a uniquely numbered metal ear tag.
The animals were housed 2 per cage in suspended wire mesh cages. Bedding was placed beneath the cages. Fresh Purina Rabbit Chow (Diet #53-21) and water were freely available.
The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled and was kept clean and vermin free.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Equivalent to 0.1 mL

Duration of treatment / exposure:

Exposure time: 72 hours

Observation period (in vivo):

Observations: 24, 48 and 72 hours after dosing.

Number of animals or in vitro replicates:

Six

Details on study design:

Experimental design
The test article was placed by syringe or syringe-type applicator into the conjunctival sac which was performed by getly pulling the loewer eye lid away from the eye. After instillation, the lids were held together briefly to ensure adequate distribution of the test article. One eye of each rabbit was dosed. The contralateral eye served as a control.

Type and frequency of observations
The treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva on Days 1, 2 and 3. Occular reactions were graded according to the numerical Draize technique. Additional signs were described. The general health of the aminals was monitored at each observation time.

Analysis of data
The primary eye irritation score for each rabbit was calculated from the weighted Draize scale.
The irritation potential was determined by counting the number of rabbits with positive irritation. Positive irritation is defined as any score for opacity or iritis or 2 or more for redness or chemosis. The test article is an irritant if 4 or more rabbits had a positive score at any time period.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

There was no corneal opacity, iritis or moderate conjunctival irritation. Four of six eyes had slight conjunctival irritation which cleared by day 3.

Other effects:

None

Rabbit No.	Item	Tissue	Reading	Day 1	Day 2	Day 3
A9544-F	A	Cornea	Opacity Area	0	0	0
	B	1. Corneal Total = (AxB)x5		0	0	0
	C	Iris 2. Iris Total = Cx5		0	0	0
	D	Conjunctiva	Redness	1	0	0
	E		Chemosis	0	0	0
	F		Discharge	0	0	0
		3. Conjunctiva Total = (D+E+F) x 2		2	0	0
	Totals added = 1+2+3			2	0	0

 

Rabbit No.	Item	Tissue	Reading	Day 1	Day 2	Day 3
A9560-M	A	Cornea	Opacity Area	0	0	0
	B	1. Corneal Total = (AxB)x5		0	0	0
	C	Iris 2. Iris Total = Cx5		0	0	0
	D	Conjunctiva	Redness	0	0	0
	E		Chemosis	0	0	0
	F		Discharge	0	0	0
		3. Conjunctiva Total = (D+E+F) x 2		0	0	0
	Totals added = 1+2+3			0	0	0

 

Rabbit No.	Item	Tissue	Reading	Day 1	Day 2	Day 3
A9565-M	A	Cornea	Opacity Area	0	0	0
	B	1. Corneal Total = (AxB)x5		0	0	0
	C	Iris 2. Iris Total = Cx5		0	0	0
	D	Conjunctiva	Redness	1	1	0
	E		Chemosis	0	0	0
	F		Discharge	1	0	0
		3. Conjunctiva Total = (D+E+F) x 2		4	2	0
	Totals added = 1+2+3			4	2	0

 

Rabbit No.	Item	Tissue	Reading	Day 1	Day 2	Day 3
A9585-F	A	Cornea	Opacity Area	0	0	0
	B	1. Corneal Total = (AxB)x5		0	0	0
	C	Iris 2. Iris Total = Cx5		0	0	0
	D	Conjunctiva	Redness	1	1	0
	E		Chemosis	0	0	0
	F		Discharge	1	1	0
		3. Conjunctiva Total = (D+E+F) x 2		4	4	0
	Totals added = 1+2+3			4	4	0

 

Rabbit No.	Item	Tissue	Reading	Day 1	Day 2	Day 3
A9667-M	A	Cornea	Opacity Area	0	0	0
	B	1. Corneal Total = (AxB)x5		0	0	0
	C	Iris 2. Iris Total = Cx5		0	0	0
	D	Conjunctiva	Redness	0	0	0
	E		Chemosis	0	0	0
	F		Discharge	1	0	0
		3. Conjunctiva Total = (D+E+F) x 2		2	0	0
	Totals added = 1+2+3			2	0	0

 

Rabbit No.	Item	Tissue	Reading	Day 1	Day 2	Day 3
A9670-M	A	Cornea	Opacity Area	0	0	0
	B	1. Corneal Total = (AxB)x5		0	0	0
	C	Iris 2. Iris Total = Cx5		0	0	0
	D	Conjunctiva	Redness	1	1	0
	E		Chemosis	0	0	0
	F		Discharge	1	0	0
		3. Conjunctiva Total = (D+E+F) x 2		4	2	0
	Totals added = 1+2+3			4	2	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: 16 CFR 1500.42.

Conclusions:

There was no corneal opacity, iritis or moderate conjunctival irritation. Four of six eyes had slight conjunctival irritation which cleared by Day 3. In conclusion the test article is a non-irritant

Executive summary:

The objective of the study was to identify the irritation potential of the test material Aminox CN 5731 when instilled into the rabbit eye. The study was conducted in accordance to GLP and FHSA 16 CFR 1500.42. Results revealed there was no corneal opacity, iritis or moderate conjunctival irritation. Four of six eyes had slight conjunctival irritation which cleared by Day 3. In conclusion the test article is not irritating to rabbit eyes.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Study not conducted according to GLP or a recognised test guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

100 mg of the test substance

Duration of treatment / exposure:

Duration of exposure: 7 days

Observation period (in vivo):

Observations were made 24, 48 and 72 hours and 7 days after exposure

Number of animals or in vitro replicates:

Six

Details on study design:

Six New Zealand White albino rabbits are used for each test substance. The animals are caged individually and receive no hay or other extraneous material that may enter the eyes.
The eyes of the animals are examined before testing and only those animals without observable eye defects are used. 100 mg of the test substance, isallowed to fall on the everted lower lid of one eye of each rabbit the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye remaining untreated, serves as a control.

The eyes are not washed following instillation and the animals are released immediately. The eyes are examined at 24, 48 and 72 hours and 7 days after instillation of the test material.

An animal is considered as giving a positive reaction if there is at any of the readings, discernible opacity of the cornea (other than a slight dulling of the normal lustre), or ulceration of the cornea, or inflammation of the iris (other than a slight deepening of the folds (rugae) or a slight circumcorneal injection), or if such substances produce in the conjunctivae (palpebral and bulbar, excluding the cornea and iris) an obvious swelling with partial eversion of the lids, or a diffuse deep-crimson red with individual vessels not easily discernible. The FDA-scoring scale is used.
The test is considered positive if four or more of the animals in the test group of six rabbits exhibit positive reaction. If one animal exhibits a positive reaction, the test is regarded as negative.
If two or three animals exhibit a positive reactions, the test is repeated, using different group of six animals. The second test is considered as positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the second test exhibit a positive reaction, the test is again repeated with a different group of six animals. Should a third test be needed, the substance will be regarded as an irritant, if two or more animals exhibit a positive response. Ocular reactions are read using a binocular magnifying glass. The diagnosis of corneal damage is confirmed, if necessary by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eyes are examined in a dark room under ultraviolet illumination. A substance which has elicited corneal and/or iris lesions which have not cleared by the seventh day reading is considered a severe eye irritant.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

24 hours after the test compound had been brought into the eyes, slight conjunctivitis was observed in five out of five rabbits. After seven days all eye lesions had recovered completed

Other effects:

None specified

Individual scores awarded to the ocular lesions elicited by WTR 9a Permanax

Time	Rabbit No.	Cornea	Iris	Conjunctivae Redness	Conjunctivae Chemosis
After 24 hours	1	0	0	1	0
	2	0	0	1	1
	3	0	0	1	0
	4	0	0	1	1
	5	0	0	0	0
	6	0	0	1	1
After 48 hours	1	0	0	0	0
	2	0	0	1	0
	3	0	0	0	0
	4	0	0	1	0
	5	0	0	0	0
	6	0	0	1	0
After 72 hours	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
	4	0	0	1	0
	5	0	0	0	0
	6	0	0	1	0
After 7 days	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
	4	0	0	0	0
	5	0	0	0	0
	6	0	0	0	0

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: Draize evaluation criteria

Conclusions:

24 hours after the test compound had been brought into the eyes, slight conjunctivitis was observed in five out of five rabbits. After seven days all eye lesions had recovered completed. According to the FDA-standards WTR 9a is not considered to be an eye irritant

Executive summary:

The aim of the study was to determine the irritancy potential of WTR 9a compound on rabbit eyes by evaluating the results using the Draize method of evaluation. The WTR 9a compound caused slight conjunctivitis in five out of six of the rabbits, but after seven days all eye lesions had recovered completely. It was concluded, based on FDA-standards that WTR 9a is not considered to be an eye-irritant.

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:

Conducted Good Laboratory Practices Regulations of the FDA effective 20/06/1979 in the US

Justification for selection of eye irritation endpoint:

Conducted Good Laboratory Practices Regulations of the FDA effective 20/06/1979 in the US

Justification for classification or non-classification

Based on the available information for the substance, in accordance with Regulation 1272/2008, the substance does not meet the classification criteria for skin corrosion/irritation or eye damage/irritation.