Registration Dossier

Skin Irritation:

No mortalities or abnormal clinical signs were observed during the study. No dermal irritation was observed during the study. Solvent Red 1 scored 0.0 on the Primary Irritation Index. Hence, Solvent Red 1 was considered to be not irritating to rabbit skin.

Eye Irritation:

No mortalities or abnormal clinical signs were observed. Redness (grade 1 through 3), chemosis (grade 1 and 2), discharge (grades 1 and 2), and iritis (grade 1) were observed. Blistering of the conjunctivae was noted for all animals. All animals were considered to have exhibited a positive response to Solvent Red 1.

Hence, Solvent Red 1 can be considered to be irritating to New Zealand White rabbit eyes.

Reference

Endpoint:: skin irritation: in vivo
Type of information:: experimental study
Adequacy of study:: key study
Reliability:: 2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:: data from handbook or collection of data
Justification for type of information:: data is from peer reviewed journals
Qualifier:: according to guideline
Guideline:: other: as mentioned below
Principles of method if other than guideline:: To assess the dermal irritation potential of Solvent Red 1 in New Zealand White rabbits
GLP compliance:: not specified
Specific details on test material used for the study:: - Name of test material: 1-[(2-methoxyphenyl)diazenyl]-2-naphthol
- Common Name: Solvent Red 1
- Molecular formula: C17H14N2O2
- Molecular weight: 278.31 g/mol
- Smiles notation: c12c(\N=N\c3c(cccc3)OC)c(ccc1cccc2)O
- InChl : 1S/C17H14N2O2/c1-21-16-9-5-4-8-14(16)18-19-17-13-7-3-2-6-12(13)10-11-15(17)20/h2-11,20H,1H3/b19-18+
- Substance type: Organic
- Physical state: Solid
Species:: rabbit
Strain:: New Zealand White
Details on test animals or test system and environmental conditions:: Details on test animal
TEST ANIMALS
- Sex: Male and female
- Source: Kuiper’s rabbit ranch, Gary, IN.
- Age at study initiation: No data available
- Weight at study initiation: 2.26 – 2.88 kg
- Fasting period before study: No data available
- Housing: Animals were housed in the appropriate randomly selected cage. Each animal was then assigned a sequential animal number unique within American Biogenics Corporation (ABC) and identified with an ear tag bearing this animal number, The sequential animal number was listed on a cage card that was affixed to the front of the animal's cage. Rooms were cleaned daily and the cages were cleaned and sanitized as specified in ABC SOP's. Urine and feces fell through the wire mesh floor onto animal caging board. The cage boards were changed at least 2 to 3 times per week.
- Diet (e.g. ad libitum): Purina Certified Rodent Chow 5002, ad libitum, except for fasting prior to dosing.

- Water (e.g. ad libitum): Filtered tap water was provided through an automatic watering system and was analyzed periodically, ad libitum.

- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 7 °C
- Humidity (%): 30-70 %
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 6:00 a.m. to 6:00 p.m. (12 hour light/dark, cycle)

IN-LIFE DATES: From: October 15, 1985 To: October 29, 1985
Type of coverage:: occlusive
Preparation of test site:: other: clipped intact and abraded skin
Vehicle:: physiological saline
Controls:: not specified
Amount / concentration applied:: Each rabbit received a dose of 0.5ml Solvent Red 1 on two intact sites and two abraded sites (the right anterior and the left posterior were abraded).
Duration of treatment / exposure:: 24 hours
Observation period:: Sites were scored at 24 and 72 hr. after application
Number of animals:: groups of 6 rabbits (3/sex)
Details on study design:: TEST SITE
- Area of exposure: Thoracic region of spinal column
- % coverage: No data available
- Type of wrap if used: 2.5 centimeter square gauze patch were used.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Each test site was gently wiped with gauze sponges moistened with an appropriate vehicle (known not to cause any dermal toxic reactions) to remove any remaining test article.
- Time after start of exposure: 24 hours

SCORING SYSTEM: The reactions were scored according to the method of Draize
The Primary Irritation Score was calculated for each test article as follows: the average scores for erythema and eschar formation for intact and abraded skin at 24 (+2) and 72 (+2) hours were added to the average scores for edema for intact and abraded skin at 24 (+2) and 72 (+2) hours. The total of the 16 values was divided by 8 to give the Primary Irritation Score.
Other effects / acceptance of results:: no data available
Irritation parameter:: primary dermal irritation index (PDII)
Basis:: mean
Time point:: 24 h
Score:: 0
Reversibility:: not specified
Remarks on result:: no indication of irritation
Irritation parameter:: primary dermal irritation index (PDII)
Basis:: mean
Time point:: 72 h
Score:: 0
Reversibility:: not specified
Remarks on result:: no indication of irritation
Irritant / corrosive response data:: No mortalities or abnormal clinical signs were observed during the study. No dermal irritation was observed during the study. Solvent Red 1 scored 0.0 on the Primary Irritation Index. Solvent Red 1 was non-irritating.
Interpretation of results:: other: not irritating
Conclusions:: No mortalities or abnormal clinical signs were observed during the study. No dermal irritation was observed during the study. Solvent Red 1 scored 0.0 on the Primary Irritation Index. Hence, Solvent Red 1 was considered to be not irritating to rabbit skin.
Executive summary:: The primary dermal irritation of Solvent Red 1 was assessed in rabbits. The backs of six New Zealand White (NZW) rabbits (three of each sex) were closely clipped 24 hours before dosing. Each rabbit received a dose of 0.5ml Solvent Red 1 on two intact sites and two abraded sites (the right anterior and the left posterior were abraded). After 24 hours of exposure, the wrappings and patches were removed and sites wiped off with gauze sponges moistened with water. Sites were scored at 24 and 72 hours after application using the method of Draize (1979).Each animal was weighed prior to application of each test article. All animals were observed at least once daily for mortality and obvious toxic signs.
No mortalities or abnormal clinical signs were observed during the study. No dermal irritation was observed during the study. Solvent Red 1 scored 0.0 on the Primary Irritation Index. Hence, Solvent Red 1 was considered to be not irritating to rabbit skin.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

To assess the eye irritation potential of Solvent Red 1 in New Zealand White rabbits

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 1-[(2-methoxyphenyl)diazenyl]-2-naphthol
- Common Name: Solvent Red 1
- Molecular formula: C17H14N2O2
- Molecular weight: 278.31 g/mol
- Smiles notation: c12c(\N=N\c3c(cccc3)OC)c(ccc1cccc2)O
- InChl : 1S/C17H14N2O2/c1-21-16-9-5-4-8-14(16)18-19-17-13-7-3-2-6-12(13)10-11-15(17)20/h2-11,20H,1H3/b19-18+
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: Male and female
- Source: Kuiper’s rabbit ranch, Gary, IN.
- Age at study initiation: No data available
- Weight at study initiation: 2.40 – 2.58 kg
- Fasting period before study: No data available
- Housing: Animals were housed in the appropriate randomly selected cage. Each animal was then assigned a sequential animal number unique within American Biogenics Corporation (ABC) and identified with an ear tag bearing this animal number, The sequential animal number was listed on a cage card that was affixed to the front of the animal's cage. Rooms were cleaned daily and the cages were cleaned and sanitized as specified in ABC SOP's. Urine and feces fell through the wire mesh floor onto animal caging board. The cage boards were changed at least 2 to 3 times per week.
- Diet (e.g. ad libitum): Purina Certified Rodent Chow 5002, ad libitum, except for fasting prior to dosing.
- Water (e.g. ad libitum): Filtered tap water was provided through an automatic watering system and was analyzed periodically, ad libitum.

- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 7 °C
- Humidity (%): 30-70 %
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 6:00 a.m. to 6:00 p.m. (12 hour light/dark, cycle)

IN-LIFE DATES: From: September 16, 1985 To: September 24, 1985

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

100 mg (0.1 ml)

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

The treated eye of each animal was examined for ocular irritation and lesions at 24, 48 and 72 hours (+2 hours at each interval). The treated eyes were evaluated on days 7, 14, and 21 if irritation persisted.

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6 (3/sex)

Details on study design:

Details on study design
TEST SITE
- Area of exposure: everted lower lid of the right eye
- % coverage: No data available
- Type of wrap if used: No data available

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data available
- Time after start of exposure: No data available

SCORING SYSTEM: according to Draize method
The mean Primary Eye Irritation Score with standard deviation and standard error values were calculated at each evaluation interval using the total scores of each treated eye.

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

10.7

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Score:

4.7

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0.7

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Redness (grade 1 through 3), chemosis (grade 1 and 2), discharge (grades 1 and 2), and iritis (grade 1) were observed.Blistering of the conjunctivae was noted for all animals. Two animals also exhibited opacities and positive fluorescein staining.

Table 1: Ocular reaction data

	Time interval	Prior to instillation			24 (± 2) hours			48 (± 2) hours			72 (± 2) hours
	No of animals	1	2	3	1	2	3	1	2	3	1	2	3
1	Cornea
	Density	0	0	0	1	0	1	0	0	0	0	0	0
	Area	0	0	0	1	0	1	0	0	0	0	0	0
	A x B x 5	0	0	0	5	0	5	0	0	0	0	0	0

2	Iris
	Value	0	0	0	1	0	1	0	0	0	0	0	0
	A x 5	0	0	0	5	0	5	0	0	0	0	0	0

3	Conjunctivae
	Redness	0	0	0	3	2	2	2	1	1	1	0	0
	Cherosis	0	0	0	2	2	2	1	0	1	0	0	0
	Discharge	0	0	0	2	1	2	0	0	0	0	0	0
	(A + B+ C) x 2	0	0	0	14	10	12	6	2	4	2	0	0

	Total 1 +2 +3	0	0	0	24	10	22	6	2	4	2	0	0
	Reaction to fluorescein				1	0	1	0	0	0	0	0	0
	Mean	0	0	0	10. 7			4.0			0.7
	S.D.	0	0	0	7.5			2.0			1.2
	S.E.	0	0	0	4.4			1.2			0.7

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

No mortalities or abnormal clinical signs were observed. Redness (grade 1 through 3), chemosis (grade 1 and 2), discharge (grades 1 and 2), and iritis (grade 1) were observed. Blistering of the conjunctivae was noted for all animals. All animals were considered to have exhibited a positive response to Solvent Red 1.
Hence, Solvent Red 1 can be considered to be irritating to New Zealand White rabbit eyes.

Executive summary:

An eye irritation study was performed on 6 (3/sex) New Zealand White Albino rabbits to assess the irritation potential of Solvent Red 1.

0.1 g of neat Solvent Red 1 was instilled into the eyes of rabbits and the effects were observed. The treated eye of each animal was examined for ocular irritation and lesions at 24, 48 and 72 hours (+2 hours at each interval). The treated eyes were evaluated on days 7, 14, and 21 if irritation persisted. No mortality and clinical signs of toxicity were observed in treated rabbits. Redness (grades 1 through 3), chemosis (grades I and 2), discharge (grades 1 and 2) and iritis (grade 1) were observed. Blistering of the conjunctivae were observed.Blistering of the conjunctivae was noted for all animals. Two animals also exhibited opacities and positive fluorescein staining. All animals were considered to have exhibited a positive response to Solvent Red 1.

The mean irritation score after 72 hours was 0.7

Hence, Solvent Red 1 can be considered to be irritating to New Zealand White rabbit eyes.

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

Skin Irritation:

In different studies, Solvent Red 1 has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its structurally similar read across substances, 1-(phenylazo)-2-napthol [CAS: 842-07-9].

Primary skin irritation study was conducted by Gunda Reddy and Dale A. Mayhew (International Journal of Toxicology, Vol 15, Issue 1_suppl, pp. S43 - S44, 1996) on 6 New Zealand White rabbits to assess the irritation potential of Solvent Red 1. The backs of six New Zealand White (NZW) rabbits (three of each sex) were closely clipped 24 hours before dosing. Each rabbit received a dose of 0.5ml Solvent Red 1 on two intact sites and two abraded sites (the right anterior and the left posterior were abraded). After 24 hours of exposure, the wrappings and patches were removed and sites wiped off with gauze sponges moistened with water. Sites were scored at 24 and 72 hours after application using the method of Draize (1979).Each animal was weighed prior to application of each test article. All animals were observed at least once daily for mortality and obvious toxic signs.

No mortalities or abnormal clinical signs were observed during the study. No dermal irritation was observed during the study. Solvent Red 1 scored 0.0 on the Primary Irritation Index. Hence, Solvent Red 1 was considered to be not irritating to rabbit skin.

This result is supported by the Primary skin irritation test of structurally similar read across substances, 1-(phenylazo)-2-napthol [CAS: 842-07-9] performed (BASF Aktiengesellschaft Gewerbehygiene und Toxikologie, 6700 Ludwigshafen, 1977) according to Guidelines mentioned in Federal Register 38 No 187 § 1500 .41 (skin). 6 rabbits were used for the study. 50% of the substance in aqueous solution was applied on the intact and scarified skin of rabbits and the effects were observed at 24 and 72 hours. The reactions were scored according to Draize method. Due to substance-induced coloration of the skin no reading and no exact calculation of the primary irritation was possible at 24 hours.

Skin lesions were also observed after 8 days of testing. No lesions were observed in case of intact skin, but dandruff formation was recorded in 4 of 6 rabbits in case of scarified skin.The Primary Skin Irritation Score of 1-phenylazo-2-naphthol was 0.17.

On the basis of the scores and observations, 1-phenylazo-2-napthol can be considered as not irritating to skin.

Based on the available data for the target and read across substances, Solvent Red 1 can be considered to be not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye Irritation:

In different studies, Solvent Red 1 has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its structurally similar read across substances, 1-({2-methyl-4-[(2-methylphenyl)diazenyl]phenyl}diazenyl)-2-naphthol (also known as Solvent Red 24) [CAS: 85-83-6] and 1-(4-(phenylazo)phenylazo)-2-naphthol also known as Solvent Red 23 [CAS:85-86-9].

Primary eye irritation study was conducted by Gunda Reddy and Dale A. Mayhew (International Journal of Toxicology, Vol 15, Issue 1_suppl, pp. S43 - S44, 1996) on 6 New Zealand White rabbits to assess the irritation potential of Solvent Red 1. 0.1 g of neat Solvent Red 1 was instilled into the eyes of 6 New Zealand White (NZW) rabbits (three of each sex) and the effects were observed. The treated eye of each animal was examined for ocular irritation and lesions at 24, 48 and 72 hours (+2 hours at each interval). The treated eyes were evaluated on days 7, 14, and 21 if irritation persisted. No mortality and clinical signs of toxicity were observed in treated rabbits. Redness (grades 1 through 3), chemosis (grades I and 2), discharge (grades 1 and 2) and iritis (grade 1) were observed. Blistering of the conjunctivae were observed.Blistering of the conjunctivae was noted for all animals. Two animals also exhibited opacities and positive fluorescein staining. All animals were considered to have exhibited a positive response to Solvent Red 1.

The mean irritation score after 72 hours was 0.7

Hence, Solvent Red 1 can be considered to be irritating to New Zealand White rabbit eyes.

This result is supported by the experimental summarized inScientific Committee on Cosmetology (seventh series), 1988; for thestructurally similar read across substance, 1-({2-methyl-4 -[(2-methylphenyl)diazenyl]phenyl}diazenyl)-2-naphthol (also known as Solvent Red 24) [CAS: 85-83-6].100 mg of Sudan IV was made into a paste with 8 drops of 1,2-propanediol and instilled into the rabbits eyes

The rabbits were observed (duration not specified) for ocular reactions to Sudan IV.

The dye was classified as slightly irritating to the mucous membranes.

These results are further supported by the experimental studyScientific Committee on Cosmetology (seventh series), for thestructurally similar read across substance, 1-(4-(phenylazo)phenylazo)-2-naphthol also known as Solvent Red 23 [CAS:85-86-9]. Upon application of 0.1 g Solvent Red 23 with 2 drops of propanediol to the rabbit eyes, Solvent Red 23 was considered to be slightly irritating to rabbit eyes.

Based on the available data for the target and read across substances, Solvent Red 1 can be considered to be irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

Available studies for Solvent Red 1 indicate that it is not likely to cause any irritation to skin and but it causes irritation to eyes.

Hence, Solvent Red 1 can be classified under the category “Not Classified” for skin and “Category 2” for eyes as per CLP.