Registration Dossier

Skin Irritation/Corrosion: No irritating effects

Eye Irritation: Mild conjuvtival erythema noted in 5/6 animals (non-rinsed eye) and 1/3 (rinsed eye), fully reversible within 48 hours.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 May 1979 to 22 June 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed in accordance with Section 162.81 of the Regulations for the Enforcement of the Federal .Insecticide, Fungicide, and Rodenticide Act, (Federal Register , Wednesday, June 25, 1975). GLP status not reported.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: Section 162.81 of the Regulations for the Enforcement of the Federal .Insecticide, Fungicide, and Rodenticide Act, (Federal Register, Wednesday, June 25, 1975).

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

New Zealand White rabbits from Willoughby's Rabbitry.
The rabbits were acclimated to the laboratory for a t least one day before they were dosed. The rabbits were individually identified by means of numbered ear tags.

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

physiological saline

Controls:

no

Amount / concentration applied:

0.5 grammes of the undiluted test material was applied, moistened with physiological saline

Duration of treatment / exposure:

24 hour

Observation period:

72 hours

Number of animals:

Six animals

Details on study design:

0.5 grames of the undiluted test material was moistened with physiological saline and applied under a one-inch square surgical gauze patch, two layers thick, to two intact skin areas and two abraded skin areas of each of six New Zealand White rabbits. The application sites were prepared by clipping the hair from the saddle area of the rabbits. The abraded areas were prepared by making minor epidermal incisions with a hypodermic needle. The abrasions were sufficiently deep penetrate the epidermis, but not to induce bleeding. Each patch was held in place with two strips on one-inch adhesive tape. After application of the patches, the truck of each rabbit was wrapped with rubber dental daming, which was secured with staples. An outer layer of gauze and tape was placed around the truck of each animal. The animals were restrained in Newmann harnesses for 24 hours.
At the end of the 24-hour exposure period, the patches were removed and any residual sample was gently wiped from the skin with a soft dry towel.
The reactions were scored immediately after removal of the patches 24-hour reading and again two day later 72-hour reading, according to the Draize scale.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

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:

24/48/72 h

Score:

0

Max. score:

4

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:

0

Max. score:

4

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:

0

Max. score:

4

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:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No irritative effects were noted at any site throughout the study.

Other effects:

None specified

Primary irritation scores in New Zealand White rabbits following a 24-hour patch application of TVCI B-5909

Skin	Time Hours	Score for Rabbit Number												Total Score	Average
		1		2		3		4		5		6
		(141)		(142)		(143)		(144)		(145)		(146)
Erythema and Eschar Formation
	Site	A	C	B	D	C	A	D	B	A	C	B	D
Intact	24 72	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
	Site	B	D	C	A	D	B	A	C	B	D	C	A
Abraded	24 72	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
Edema Formation
	Site	A	C	B	D	C	A	D	B	A	C	B	D
Intact	24 72	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
	Site	B	D	C	A	D	B	A	C	B	D	C	A
Abraded	24 72	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
Primary Irritation Index 0

Site Key – Dorsal View of Rabbit

Head
A	C
B	D
Tail

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

TVCI B-5909 produced no irritating effects following application to the intact and abraded skin of New Zealand White rabbits.

Executive summary:

The purpose of this study was to evaluate the acute dermal irritation potential of the test material in accordance with Section 162.81 of the Regulations for the Enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act, (Federal Register, Wednesday, June 25, 1975).

0.5g of the undiluted test material was moistened with and applied to two intact skin areas and two abraded skin areas on each of six New Zealand White rabbits.

At the end of the 24-hour exposure period, the patches were removed and any residual sample was gently wiped from the skin with a soft dry towel.

The reactions were scored immediately after removal of the patches 24-hour reading, and again two days later 72-hour reading.

TVCI B-5909 produced no irritating effects following application to the intact and abraded skin of New Zealand White rabbits.

The primary irritation index was found to be 0.

Based on these results TVCI B-5909 is classified in Toxicity IV for skin effects as these categories are described in Section 162.10 of the above-ci ted Regulations (Federal Register, Thursday, July 3, 1975). This corresponds to "not irritating" under The CLP Regulation. European Regulation (EC) No 1272/2008.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 May 1979 to 22 June 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed in accordance with Section 162.81 of the Regulations for the Enforcement of the Federal .Insecticide, Fungicide, and Rodenticide Act, (Federal Register , Wednesday, June 25, 1975). No reference to GLP status.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: Section 162.81 of the Regulations for the Enforcement of the Federal .Insecticide, Fungicide, and Rodenticide Act, (Federal Register, Wednesday, June 25, 1975).

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Nine New Zealand White rabbits from Plummer's Rabbit Ranch were used in this study. The rabbits were identified individually by means of numbered ear tags, and were acclimated to the laboratory for at least 5 days prior to being dosed.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.73 gram of the test material (weight of volume occupying 0.1 ml )

Duration of treatment / exposure:

Single application.
The treated eyes of 6 rabbits were left unrinsed, the treated eyes of 3 rabbits were rinsed after 30 seconds for 60 seconds with 200 ml of lukewarm tap water.

Observation period (in vivo):

Examinations for gross signs of eye irritation were made at 24 hrs., 48 hrs., and 72 hrs., 4 days and 7 days following application.

Number of animals or in vitro replicates:

9 animals

Details on study design:

1 and 0.25 hours before being dosed, sodium fluorescein (2%) was used in both eyes of each rabbit to assure no corneal opacity was present prior to dosing.
0.73 gram of the test material (weight of volume occupying 0.1 ml) was applied to the right eye of each of the 9 rabbits. The left eyes were untreated and served as controls. The treated eyes of 6 rabbits were left unrinsed, the treated eyes of 3 rabbits were rinsed after 30 seconds for 60 seconds with 200 ml of lukewarm tap water. Examinations for gross signs of eye irritation were made at 24 hrs., 48 hrs., and 72 hrs., 4 days and 7 days following application. Scoring of irritative effects was according to the method of Draize, in which corneal, iris and conjunctival effects are scored separately.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animals# 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animals# 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animals# 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animals# 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animals# 7-9

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animals# 7-9

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animals# 7-9

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animals# 7-9

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Non-Rinsed Eyes
Irritative effects noted at the 24-hour reading included mild conjunctival erythema in five rabbits. By the 48-hour reading and throughout the rest of the study no irritative effects were noted.
Rinsed Eyes
Irritative effects noted at the 24-hour reading included mild conjunctival erythema in one rabbit. By the 48-hour reading and throughout the rest of the study no irritative effects were noted.

Other effects:

None specified

Eye irritation scores in albino rabbits following application of 0.73 gr. of TVCI B-5909 without a subsequent water rinse

Rabbit Number

Time

Cornea

Iris

Conjunctivae

Total Score*

Days

Opacity

Area

Erythema

Swelling

Discharge

1

(117)

1

2

3

4

7

0

1

0

2

0

2

(18)

1

2

3

4

7

0

1

0

2

0

3

(35)

1

2

3

4

7

0

4

(136)

1

2

3

4

7

0

1

0

2

0

5

(137)

1

2

3

4

7

0

1

0

2

0

6

(138)

1

2

3

4

7

0

1

0

2

0

*Total score is sum of the following three sub-totals:

(a) degree of opacity x area involved x 5

(b) iris score x 5

(c) sum of scores for erythema, swelling and discharge x 2

Total possible score = 110

Eye irritation scores in albino rabbits following application of 0.73 gr. of TVCI B-5909 with subsequent water rinse after 30 seconds for 60 seconds in 200 ml tap water

Rabbit Number

Time

Cornea

Iris

Conjunctivae

Total Score*

Opacity

Area

Erythema

Swelling

Discharge

7

(139)

1

2

3

4

7

0

1

0

2

0

8

(125)

1

2

3

4

7

0

9

(123)

1

2

3

4

7

0

*Total Score is the sum if the following three sub-totals:

(a) degree of opacity x area involved x 5

(b) iris score x 5

(c) sum of scores for erythema, swelling and discharge x 2

Total possible score = 110

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Mild conjunctival erythema was noted in five rabbits with non-rinsed eyes and in one rabbit with a rinsed eye at the 24-hour reading.

Executive summary:

The purpose of this study was to evaluate the eye irritation potential of the test material in accordance with Section 162.81 of the Regulations for the Enforcement of the Federal .Insecticide, Fungicide, and Rodenticide Act, (Federal Register, Wednesday, June 25, 1975).

Nine New Zealand White rabbits were used in the study.

0.73 gram of the test material (weight of volume occupying 0.1 ml) was applied to the right eye of each of the 9 rabbits. The left eyes were untreated and served as controls. The treated eyes of 6 rabbits were left unrinsed, the treated eyes of 3 rabbits were rinsed after 30 seconds for 60 seconds with 200 ml of lukewarm tap water. Examinations for gross signs of eye irritation were made at 24 hrs., 48 hrs., and 72 hrs., 4 days and 7 days following application. Scoring of irritative effects was according to the method of Draize.

Mild conjunctival erythema was noted in five rabbits with non-rinsed eyes and in one rabbit with a rinsed eye at the 24-hour reading.

Based on these results TVCI B-5909 is classified in Toxicity Category III for eye effects as these categories are described in Section 162.10 of the above-cited Regulations (Federal Register, Thursday, July 3, 1975). This corresponds to "not irritating" under The CLP Regulation. European Regulation (EC) No 1272/2008.

Endpoint conclusion:

no adverse effect observed (not irritating)

Skin Irritation/Corrosion

The purpose of this study was to evaluate the acute dermal irritation potential of the test material.

Five-tenths gram of the undiluted test material was moistened with and applied to two intact skin areas and two abraded skin areas on each of six New Zealand White rabbits.

At the end of the 24-hour exposure period, the patches were removed and any residual sample was gently wiped from the skin with a soft dry towel.

The reactions were scored immediately after removal of the patches 24-hour reading, and again two days later 72-hour reading.

TVCI B-5909 produced no irritating effects following application to the intact and abraded skin of New Zealand White rabbits.

The primary irritation index was found to be 0.

Eye Irritation

The purpose of this study was to evaluate the eye irritation potential of the test material.

Nine New Zealand White rabbits were used in the study.

0.73 gram of the test material (weight of volume occupying 0.1 ml) was applied to the right eye of each of the 9 rabbits. The left eyes were untreated and served as controls. The treated eyes of 6 rabbits were left unrinsed, the treated eyes of 3 rabbits were rinsed after 30 seconds for 60 seconds with 200 ml of lukewarm tap water. Examinations for gross signs of eye irritation were made at 24 hrs., 48 hrs., and 72 hrs., 4 days and 7 days following application. Scoring of irritative effects was according to the method of Draize.

Mild conjunctival erythema was noted in five rabbits with non-rinsed eyes and in one rabbit with a rinsed eye at the 24-hour reading.

Justification for selection of skin irritation / corrosion endpoint:

Study performed in accordance with Section 162.81 of the Regulations for the Enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act, (Federal Register, Wednesday, June 25, 1975).

Justification for selection of eye irritation endpoint:

Study performed in accordance with Section 162.81 of the Regulations for the Enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act, (Federal Register, Wednesday, June 25, 1975).

Skin Irritation/Corrosion

Based on these results TVCI B-5909 is classified in Toxicity IV for skin effects as these categories are described in Section 162.10 of the above-cited Regulations (Federal Register, Thursday, July 3, 1975). This corresponds to "not irritating" under The CLP Regulation. European Regulation (EC) No 1272/2008.

Eye Irritation

Based on the results TVCI B-5909 is classified in Toxicity Category III for eye effects as these categories are described in Section 162.10 of the Regulations (Federal Register, Thursday, July 3, 1975). This corresponds to "not irritating" under The CLP Regulation. European Regulation (EC) No 1272/2008.