2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone

Endpoint summary

Description of key information

Repeated dose toxicity: Oral 
The toxicity of 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone after repeated  administration by oral route was estimated using QSAR Toolbox 3.3.
The no observed effect level (NOEL) for 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone in a 13 week study in F344 rats was estimated to be 305.7 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

The prediction is using QSAR toolbox version 3.3 with log Kow as per primary discriptor

GLP compliance:

not specified

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: feed

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:not reportedBasis:no data

No. of animals per sex per dose:

10

Control animals:

yes

Dose descriptor:

NOEL

Effect level:

305.709 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects were observed

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and (("h" or "i" or "j" or "k" or "l" )  and ("m" and ( not "n") )  )  and (("o" or "p" or "q" or "r" or "s" )  and ("t" and ( not "u") )  )  )  and "v" )  and ("w" and "x" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Hydrazines and Related Compounds by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic AND Overlapping groups AND Phenol by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Hydrazine [>N-N<] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isothiocyanates OR Acylation >> P450 Mediated Activation to Acyl Halides OR Acylation >> P450 Mediated Activation to Acyl Halides >> 1,1-Dihaloalkanes OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Thiazolidinediones OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> 5-alkoxyindoles OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated aldehydes OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Thiazoles OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Carbenium Ion Formation >> Alpha halo ethers (including alpha halo thioethers) OR SN1 >> Carbenium Ion Formation >> Diazoalkanes OR SN1 >> Carbenium Ion Formation >> Hydrazine OR SN1 >> Carbenium Ion Formation >> N-Nitroso (alkylation) OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Carbenium Ion Formation >> Triazenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic N-hydroxylamines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic nitroso OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitro OR SN1 >> Nitrosation-SN1 OR SN1 >> Nitrosation-SN1 >> N-Nitroso-SN1 OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Aziridines OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Phenoxy polarised alkenes OR SN2 >> Nitrosation-SN2 OR SN2 >> Nitrosation-SN2 >> Nitroso-SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> Ring opening SN2 Reaction OR SN2 >> Ring opening SN2 Reaction >> Lactones OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphonic esters by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Hydrazines and Related Compounds by US-EPA New Chemical Categories

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol by Organic Functional groups

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic AND Overlapping groups AND Phenol by Organic Functional groups (nested)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Hydrazine [>N-N<] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Hydrazines and Related Compounds by US-EPA New Chemical Categories

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic AND Overlapping groups AND Phenol by Organic Functional groups (nested)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Hydrazine [>N-N<] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aromatic compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Sulphonyl halides OR Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isothiocyanates OR Acylation >> Isocyanates and Related Chemicals >> Thiocyanates-Acylation OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Acylation >> Ring Opening Acylation >> beta-Lactones-Acylation OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - aldehydes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - cyano OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Polarised Alkenes >> Polarised alkene - nitro OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines OR Michael addition >> Polarised Alkenes >> Polarised alkene - sulfinyl OR Michael addition >> Polarised Alkenes >> Polarised alkene - sulfonate OR Michael addition >> Polarised Alkenes >> Polarised alkene - sulfone OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Benzoquinones OR Michael addition >> Quinones and Quinone-type Chemicals >> Pyranones (and related nitrogen chemicals) OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-diimine OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-2-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-3-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SN2 OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> Ring Opening SN2 Reaction OR SN2 >> Ring Opening SN2 Reaction >> beta-Lactones-SN2 OR SN2 >> SN2 reaction at a nitrogen atom OR SN2 >> SN2 reaction at a nitrogen atom >> Nitrosoguanidine (nitrogen) OR SN2 >> SN2 reaction at a nitrogen atom >> Nitrosoureas (nitrogen) OR SN2 >> SN2 reaction at a sp2 carbon atom OR SN2 >> SN2 reaction at a sp2 carbon atom >> Polarised alkenes with a halogen leaving group OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at a sulphur atom >> Thiocyanates-SN2 OR SN2 >> SN2 reaction at a sulphur atom >> Thiols OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Haloalkenes (and related cyano, sulfate and sulfonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SN2 >> SN2 reaction at sp3 carbon atom >> beta-Halo ethers OR SN2 >> SN2 reaction at sp3 carbon atom >> Nitrosoureas (carbon) OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphonates OR SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.48

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.24

Conclusions:

The no observed effect level (NOEL) for 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone in a 13 week study in F344 rats was estimated to be 305.7 mg/kg bw/day.

Executive summary:

The toxicity of 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone after repeated administration by oral route was estimated using QSAR Toolbox 3.3.

The no observed effect level (NOEL) for 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone in a 13 week study in F344 rats was estimated to be 305.7 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

305.7

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is of K2 level predicted using OECD QSAR toolbox 3.3

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Prediction data for the target chemical and data from read across are summarized below to determine the toxic nature of the test compound

2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone upon repeated exposure.

The toxicity of 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone after repeated administration by oral route was estimated using QSAR Toolbox 3.3 (2016).

The no observed effect level (NOEL) for 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone in a 13 week study in F344 rats was estimated to be 305.7 mg/kg bw/day.

In 14 day repeated dose toxicity study (NTP, 1982), B6C3F₁male and female mice treated with C. I. Solvent Yellow 14 (RA CAS no 842-07-9) in the concentration of 0, 6,000, 12,500, 25,000, 50,000, or 100,000 ppm orally in diet. All male and female mice were died at 12500, 25000, 50000 and 100000 ppm dose. In addition, severe gross pathological effects such as dark red intestines and mildly congested livers were observed at 12500 ppm and at higher doses. Therefore, LOAEL was considered to be 12500 ppm (2500 mg/kg/day) when B6C3F₁male and female mice were treated with C. I. Solvent Yellow 14 orally in diet for 14 days. 

In 91 day repeated dose toxicity study (NTP, 1982), B6C3F₁male and female mice treated with C. I. Solvent Yellow 14 (RA CAS no 842-07-9) in the concentration of 0, 500, 1,000, 2,000, 4,000 and 8,000 ppm orally in diet. All male and 5 female mice were died on treatment of 8000 ppm. Mean body weight gain was decreased on treatment of 2000, 4000 and 8000 ppm. In addition, Splenic, renal and hepatic hemosiderosis and splenic congestion, necrosis, regeneration of renal cortical tubular epithelium and lymphoid depletion of the thymus were observed on treatment of2,000 and 4,000 ppm. Therefore, LOAEL was considered to be2000 ppm (333.4 mg/kg/day) whenB6C3F₁male and female mice were treated with C. I. Solvent Yellow 14 orally in diet for 91 days. 

In chronic repeated dose toxicity study(NTP, 1982), when B6C3F₁male and female mice treated with C. I. Solvent Yellow 14(RA CAS no 842-07-9)in the concentration of 0, 500 and 1,000 ppm orally in diet. No effect was observed on survival, clinical sign and food consumption of all treated mice as compared to control. Slightly decreased in mean body weight were observed in 500 and 1000 ppm after week 30 in males and after week 50 in females as compared to control. In addition, non neoplastic lesion such as Alveolar/Bronchiolar adenoma of lung and malignant lymphoma of hematopoietic system, hepatocellular adenoma and hepatocellular carcinoma of Liver and follicular-cell adenoma of thyroid and neoplastic lesion such as Leukemia and malignant lymphomas of various types and in various locations were observed in treated mice. But, each type of tumor represented has been encountered previously as a spontaneous lesion in aging B6C3F₁mice and considered as non carcinogenic for mice. Therefore, NOAEL was considered to be 500 ppm (71.5 mg/kg/day) when B6C3F₁male and female mice treated with C. I. Solvent Yellow 14 orally in diet for 105 weeks.

In 14 day repeated dose toxicity study (NTP, 1982), F344/N male and female rat treated with C. I. Solvent Yellow 14 (RA CAS no 842-07-9) in the concentration of 0, 6,000, 12,500, 25,000, 50,000 and 100,000 ppm orally in diet.1 male and 1 female were died at 6000 ppm dose. All male and female rat were died at 12500, 25000, 50000 and 100000 ppm dose. In addition, severe gross pathological effects such as dark red intestines and mildly congested livers were observed at 6000 ppm and at higher doses. Therefore, LOAEL was considered to be 6000 ppm (600 mg/kg/day) whenF344/N male and female rat were treated with C. I. Solvent Yellow 14 orally in diet for 14 days. 

In 91 day repeated dose toxicity study (NTP, 1982), F344/N male and female rat treated with C. I. Solvent Yellow 14 (RA CAS no 842-07-9) in the concentration of 0, 250, 500, 1,000, 2,000 and 4,000 ppm orally in diet. No effect was observed on survival of treated ra as compared to control. Decrease mean body weight was observed in1000, 2000 and 4000 ppm treated rat. Similarly, food consumption was decreased in 2000 and 4000 ppm treated rat as compared to control. In addition, Hepatic degeneration characterized by increased basophilia and a granular appearance of hepatocytes adjacent to the portal areas, while centrilobular hepatocytes had a hazy, almost vacuolated appearance were observed in 4000 ppm treated dose group and Pigment deposition in the tubular epithelium of the kidney cortex of 1000 ppm dose treated male and 500 ppm treated female were observed as compared to control. Therefore, LOAEL was considered to be 1000 ppm (100 mg/kg/day) whenF344/N male and female rat were treated with C. I. Solvent Yellow 14 orally in diet for 91 days.  

 

In chronic repeated dose toxicity study (NTP, 1982), whenF344/N male and female rat treated with C. I. Solvent Yellow 14 (RA CAS no 842-07-9) in the concentration of 0, 250 and 500 ppm orally in diet. No effect was observed on survival, clinical sign and food consumption of all treated rat as compared to control. Decreased mean body weight was observed in 250 and 500 ppm treated rat as compared to control. In addition, Non neoplastic lesions such as multifocal fibrosis of the cardiac valve, lymphoid hyperplasia of the lung in male rats and bile duct focal hyperplasia in female rats, atrophy of the pancreatic acinus, nephropathy and composed of eosinophilic or basophilic hepatocytes and accompanied by anangiectactic or cystic change small and multiple neoplastic nodules of the liver were observed in 250 and 500 ppm treated rat. Therefore, LOAEL was considered to be 250 ppm (12.5 mg/kg/day) whenF344/N male and female rat treated with C. I. Solvent Yellow 14 orally for 104 weeks.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The toxicity of 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone after repeated administration by oral route was estimated using QSAR Toolbox 3.3.
The no observed effect level (NOEL) for 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone in a 13 week study in F344 rats was estimated to be 305.7 mg/kg bw/day.

Justification for classification or non-classification

The chemical 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone was not likely to be toxic in a repeated exposure toxicity study by the oral route.