1-phenylazo-2-naphthol

Endpoint summary

Description of key information

Acute toxicity: oral

LD50 was considered to be > 10000 mg/kg bw when rats were treated with 1-phenylazo-2-naphthol (Sudanorange R) as a 5-35% suspension in 0.5% aqueous CMC preparation orally by gavage. 

Acute toxicity: inhalation

LD50 was considered to be > 200000 mg/m3 in air when rats were exposed with 1-phenylazo-2-naphthol (Sudanorange R) by inhalation route.

Acute toxicity: dermal

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) in rabbits by the dermal route. 50% mortality was observed at 2962.15 mg/kg bw in treated rabbit.The acute dermal median lethal dose (LD50) of 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) in rabbit was estimated to be 2962.15 mg/kg bw. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) does not classify as an acute dermal toxicant.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Data is from study report

Principles of method if other than guideline:

Acute oral toxicity study of Sudanorange R (fest ) in rats

GLP compliance:

not specified

Test type:

other: No data

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report):C. I. Solvent Yellow 14
- Molecular formula : C16H12N2O
- Molecular weight: 248.284 g/mole
- Substance type: Organic
- Physical state: Solid
- Purity :98%
- Impurities (identity and concentrations): 2%

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10000 mg/kg/day
- Amount of vehicle (if gavage): 5-35% suspension
- Justification for choice of vehicle: 0.5% aqueous CMC preparation
- Lot/batch no. (if required): No data available
- Purity: No data available

MAXIMUM DOSE VOLUME APPLIED: No data available

DOSAGE PREPARATION (if unusual): 5-35% suspension in 0.5% aqueous CMC preparation

Doses:

10000 mg/kg bw

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data available
- Necropsy of survivors performed: yes
- Other examinations performed: Mortality was examined.

Statistics:

No data available

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

No mortality observed

Mortality:

No mortality was observed in treated rat at 10000 mg/kg bw

Clinical signs:

skin, feces and urine orange discolored were observed in treated rats.

Body weight:

No data available

Gross pathology:

No data available

Other findings:

No data available

Interpretation of results:

other: Not classified

Conclusions:

LD50 was considered to be > 10000 mg/kg bw when rats were treated with 1-phenylazo-2-naphthol (Sudanorange R) as a 5-35% suspension in 0.5% aqueous CMC preparation orally by gavage.

Executive summary:

In a acute oral toxicity study, rats were treated wtih 1-phenylazo-2-naphthol (Sudanorange R) in the concentration of 10000 mg/kg bw as a 5-35% suspension in 0.5% aqueous CMC preparation orally by gavage and observed for 14 days. No mortality was observed in treated rat at 10000 mg/kg bw and skin, feces and urine orange discolored were observed in treated rats. Therefore, LD50 was considered to be > 10000 mg/kg bw when rats were treated with 1-phenylazo-2-naphthol (Sudanorange R) as a 5-35% suspension in 0.5% aqueous CMC preparation orally by gavage. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

Data is Klimisch 1 and from study report

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Data is from study report

Principles of method if other than guideline:

Acute inhalation toxicity study of 1-phenylazo-2-naphthol (Sudanorange R) in rats

GLP compliance:

not specified

Test type:

fixed concentration procedure

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): 1-phenylazo-2-naphthol (Sudanorange R)
- Molecular formula:C16H12N2O
- Molecular weight:248.284 g/mole
- Substance type:Organic
- Physical state: Solid
- Purity: 98%
- Impurities (identity and concentrations): 2%

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

air

Remark on MMAD/GSD:

No data available

Details on inhalation exposure:

200 L of air / h are passed through a 5 cm high layer of the product.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

8 h

Remarks on duration:

for 3,10 and 30 min and 1,3 and 8 hours

Concentrations:

200 L

No. of animals per sex per dose:

12

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 8 hours

Statistics:

No data available

Preliminary study:

No data available

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 200 000 mg/m³ air

Based on:

test mat.

Exp. duration:

8 h

Remarks on result:

other: No mortality observed

Mortality:

No mortality observed in treated rats at 200000 mg/m3

Clinical signs:

other: No data available

Body weight:

No data available

Gross pathology:

No data available

Other findings:

No data available

Mortality x / y deceased / exposed animals

Exposure time	3'	10'	30'	1 h	3 h	8h
Steam
Volatile constituents
Staub						0/12 R

Interpretation of results:

other: Not classified

Conclusions:

LC50 was considered to be > 200000 mg/m3 of air when rats were exposed with 1-phenylazo-2-naphthol (Sudanorange R) by inhalation route.

Executive summary:

In a acute inhalation toxicity study, rats were expose with 1-phenylazo-2-naphthol (Sudanorange R) in the concentration of 200000 mg/m3 / h inhaled through a 5 cm high layer of the product and observed for 8 hours. No mortality was observed in treated rat at 200000 mg/m3 / h. Therefore, LC50 was considered to be > 200000 mg/m3 of air when rats were exposed with 1-phenylazo-2-naphthol (Sudanorange R) by inhalation route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

200 000 mg/m³

Quality of whole database:

Data is Klimisch 1 and from study report

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Prediction is done using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached.

Qualifier:

no guideline available

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3 with log kow as the primary descriptor.

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report):C. I. Solvent Yellow 14
- Molecular formula : C16H12N2O
- Molecular weight: 248.284 g/mole
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

not specified

Sex:

male/female

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

No data available

Duration of exposure:

No data available

Doses:

2962.15 mg/kg bw.

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 962.15 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed.

Mortality:

50% mortality observed at 2962.15 mg/kg bw in treated rabbit.

Clinical signs:

No data available

Body weight:

No data available

Gross pathology:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and "j" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.06

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.96

Interpretation of results:

other: Not classified

Conclusions:

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) in rabbits by the dermal route. 50% mortality was observed at 2962.15 mg/kg bw in treated rabbits.The acute dermal median lethal dose (LD50) of 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) in rabbit was estimated to be 2962.15 mg/kg bw.

Executive summary:

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) in rabbits by the dermal route. 50% mortality was observed at 2962.15 mg/kg bw in treated rabbit.The acute dermal median lethal dose (LD50) of 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) in rabbit was estimated to be 2962.15 mg/kg bw. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) does not classify as an acute dermal toxicant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 962.15 mg/kg bw

Quality of whole database:

The data is Klimicsh 2 and from OECD QSAR toolbox version 3.3 (2017).

Additional information

Acute toxicity: oral

Based on the data available for target substance 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) is summarized below:

In a study conducted by BASF Company (1977), acute oral toxicity was evaluated in rats by using 1-phenylazo-2-naphthol (Sudanorange R) in the concentration of 10000 mg/kg bw as a 5-35% suspension in 0.5% aqueous CMC preparation orally by gavage and observed for 14 days. No mortality was observed in treated rat at 10000 mg/kg bw and skin, feces and urine orange discolored were observed in treated rats. Therefore, LD50 was considered to be > 10000 mg/kg bw when rats were treated with 1-phenylazo-2-naphthol (Sudanorange R) as a 5-35% suspension in 0.5% aqueous CMC preparation orally by gavage. 

In a study conducted by National Toxicology Program (1982) and National Technical Information Service (1981), acute oral toxicity was evaluated in F344 male and female rats and B6C3F1 male and female mice were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) in the concentration of 0, 600, 1250, 2500, 5000 and 10000 mg/kg/day and 0, 1200, 2500, 5000, 1000 and 20000 mg/kg/day orally in feed and observed for 14 days. No effect on survival and signs of toxicity were observed in treated mice and rat. Therefore, LD50 was considered to be > 10000 mg/kg bw for rats and > 20000 ma/kg bw for mice when F344 male and female rats and B6C3F1 male and female mice were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) orally by feed. 

Based on the predication done by using QSAR Toolbox 3.4 (2017), acute oral toxicity was estimated in rats by using 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) orally. 50 % mortality was observed in treated rat at 4455.9 mg/kg bw. Therefore, estimated LD50 was considered to be 4455.9 mg/kg bw when rats were treated with 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) orally.

In a study conducted by Tsudaet al(2000), acute oral toxicity was evaluated in DDY male mice by using 1-phenylazo-2-naphthol (Sudan I) in the concentration 1000 mg/kg orally by gavage in Olive oil. No effect on survival and clinical sign were observed in treated male mice at 1000 mg/kg bw. Therefore, LD50 was considered to be > 1000 mg/kg bw when DDY male mice were treated with 1-phenylazo-2-naphthol (Sudan I) orally by gavage in Olive oil. Data is not conclusive based on the criteria mentioned in CLP Regulation.

Based on the data available for target substance, 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS no 842-07-9) is likely to be non hazardous by oral route of exposure i.e it does not classify as an acute oral toxicant based on CLP regulation.

Acute toxicity: inhalation

Based on the data available for target substance 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) is summarized below:

In a study conducted by BASF Company (1977), acute inhalation toxicity was evaluated in rats by using 1-phenylazo-2-naphthol (Sudanorange R) in the concentration of 200000 mg/m3 / h inhaled through a 5 cm high layer of the product and observed for 8 hours. No mortality was observed in treated rat at 200000 mg/m3 / h. Therefore, LD50 was considered to be > 200000 mg/m3 in air when rats were exposed with 1-phenylazo-2-naphthol (Sudanorange R) by inhalation route.

Based on the data available for target substance, 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) is likely to be non hazardous by inhalation route of exposure i.e it does not classify as an acute toxicant by the inhalation route based on CLP regulation.

Acute toxicity: dermal

In different studies, 1-phenylazo-2-naphthol (CAS No.- 842 -07 -9) has been reviewed for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits for 1-phenylazo-2-naphthol along with the study available on structurally similar read across substances 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs (CAS No. – 70879-65-1) and Solvent Red 1 (1-[(2-methoxyphenyl)diazenyl]-2-naphthol) (CAS: 1229-55-6). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

 

The acute toxicity study was predicted by SSS (2017) using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) in rabbits by the dermal route. 50% mortality was observed at 2962.15 mg/kg bw in treated rabbit.The acute dermal median lethal dose (LD50) of 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) in rabbit was estimated to be 2962.15 mg/kg bw.

 

This is supported by the acute dermal toxicity study of structurally similar read across substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs conducted by Sustainability Support Services (Europe) AB, at IIRT (2012), Wistar male and female rats were treated with 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs in the concentration of 2000 mg/kg bw by dermal application. No mortality and any clinical signs of toxicity were observed throughout the observation period of 14 days in treated rats. The body weight of each animal recorded on day 0, 7th and 14th showed normal increase and there was no significant increase or decrease in weight was recorded. Therefore, LD50 was considered to be > 2000 mg/kg bw when Wistar male and female rats were treated with 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs by dermal application.

 

Moreover, in the study conducted byGunda Reddy et al.,( International Journal of Toxicology Vol 15, Issue 1_suppl, pp. S43 - S44, 1996), New Zealand White male and female rabbits were treated with Solvent Red 1 (1-[(2-methoxyphenyl)diazenyl]-2-naphthol) in the concentration of 5000 mg/kg bw in physiological saline applied on dorsal and lateral trunk (approximately 10% of the body surface area) of each animal was clipped free of hair with Oster electric clippers equipped with a number 40 (surgical) blade for 24 hours. No mortality was observed in treated rabbits. Red stain on teat site, feet and head discolored red in treated male and female rabbits. Few stools and loose stool were observed in treated male rabbits. Overall body weight increased was observed in treated male and female rabbits. Red discoloration of treated skin, red discoloration of fur, a liver with a dark red discoloration, and 2 lungs with red discoloration was observed in treated male and female rabbits. Therefore, LD50 was considered to be > 2000 mg/kg bw when New Zealand White male and female rabbits were treated with Solvent Red 1 (1-[(2-methoxyphenyl)diazenyl]-2-naphthol) by dermal application for 24 hours.

Thus, based on the above studies and predictions on 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) and its read across substances, it can be concluded that LD50 value is > 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, it infers that 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. 842-07-9) does not classify as an acute dermal toxicant i.e it is acutely non toxic to animals.

Justification for classification or non-classification

Based on the above mentioned studies on 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. – 842-07-9), it can be found that LD50 (oral and dermal) and LC50 (inhalation) value is greater than 2000 mg/kg b.wt. and >5 mg/L. Thus, by comparing these studies with the criteria of CLP regulation, it infers that the test substance 1-phenylazo-2-naphthol (C. I. Solvent Yellow 14) (CAS No. – 842-07-9) does not classify as an acute toxicant (by oral, inhalation and dermal route).