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

Endpoint summary

Description of key information

The test substance Yellow 101 is not likely to be toxic to rats and rabbits by oral, inhalation and dermal route, respectively.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from BASF study reports

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Acute oral toxicity test of Lumogen LT light yellow in rat by single exposure.

GLP compliance:

not specified

Test type:

other: no data

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No details available

Route of administration:

oral: unspecified

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE- Concentration in vehicle: 15% suspention- Amount of vehicle (if gavage): 0.5% aqueous solution

Doses:

4600 mg/kg

No. of animals per sex per dose:

No details available

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Clinical sign observed - Necropsy of survivors performed:NO- Other examinations performed: No details available

Statistics:

No data

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 4 600 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

no mortality observed in treated rats.

Clinical signs:

other: Yellow colored feces were observed in treated rats.

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

LD50 was considered to > 4600 mg/kg bw when rats were treated with Lumogen LT light yellow orally.

Executive summary:

In a acute oral toxicity study, rats treated with Lumogen LT light yellow at 4600 mg/kg bw in 0.5% aqueous carboxymethylcellulose preparation by single exposure and animals were observed for 14 days. No effect on survival of treated rats was observed. Yellow colored feces were observed in treated rats. Therefore, LD50 was considered to > 4600 mg/kg bw when rats were treated with Lumogen LT light yellow orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 600 mg/kg bw

Quality of whole database:

Experimental result; Data purchased from BASF and hence the data is considered to be reliable without restriction.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

other: Data is of Klimish 2 and from QSAR toolbox version 3.3

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

equivalent or similar to guideline

Guideline:

other: as mention below

Principles of method if other than guideline:

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

GLP compliance:

not specified

Test type:

other: Estimated method

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Type of coverage:

not specified

Vehicle:

not specified

Duration of exposure:

24 hours

Doses:

no data available

No. of animals per sex per dose:

Five animals per sex

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 247.018 mg/kg bw

Based on:

test mat.

The prediction was based on dataset comprised from the following descriptors: LD50
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 ("g" and ( not "h") )  )  and "i" )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and "n" )  )

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 Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Quinoide type compounds OR Michael Addition >> Quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Alkylarylether OR Amine OR Anion OR Aryl bromide OR Aryl chloride OR Aryl halide OR Azo compound OR Carbonic acid derivative OR Carbonyl compound OR Carboxylic acid OR Carboxylic acid derivative OR Carboxylic acid ester OR Carboxylic acid salt OR Cation OR CO2 derivative (general) OR Dialkylether OR Ether OR Halogen derivative OR Heterocyclic compound OR Hydrazine derivative OR Ketone OR Nitro compound OR Primary amine OR Primary aromatic amine OR Sulfonic acid derivative OR Sulfuric acid derivative OR Tertiary amine OR Tertiary mixed amine OR Thioether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.25

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.99

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The acute median lethal dose (LD50) value for 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone in F344 rats is estimated to be 4247 mg/kg bw.

Executive summary:

The acute median lethal dose (LD50) of 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone by dermal route was estimated using QSAR Toolbox 3.3.

The LD50 value for 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone in F344 rats is estimated to be 4247 mg/kg bw by dermal route of exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 247 mg/kg bw

Quality of whole database:

Data is of K2 level predicted using OECD QSAR Toolbox 3.3.

Additional information

Target CAS no. 2387-03-3 - C.I. Pigment Yellow 101: Summary

Acute oral toxicity:

In a study report given by BSF (1977), acute oral toxicity was evaluated in rats by using Lumogen LT light yellow at 4600 mg/kg bw in 0.5% aqueous carboxymethylcellulose preparation by single exposure and animals were observed for 14 days. No effect on survival of treated rats was observed. Yellow colored feces were observed in treated rats. Therefore, LD50 was considered to > 4600 mg/kg bw when rats were treated with Lumogen LT light yellow orally.

Based on the prediction done by using QSAR toolbox version 3.3 (2016), acute oral toxicity was estimated in Sprague-Dawley male and female rats by using 1-Naphthalenecarboxaldehyde, 2-hydroxy-, [(2-hydroxy-1-naphthalenyl) methylene] hydrazine orally by gavage in 1% methylcellulose. The estimated LD50 was found to be 3894.559814453 mg/kg bw when Sprague-Dawley male and female rats were treated with 1-Naphthalenecarboxaldehyde, 2-hydroxy-, [(2-hydroxy-1-naphthalenyl) methylene] hydrazine orally by gavage.

In a study conducted by Kodak Laboratory Chemicals (1960) for read across, acute oral toxicity was evaluated in rat in the concentration of 50-3200 mg/kg in NaCS by Standard acute method. Slight weakness and vasodialation were observed in treated rats. Therefore, LD50 was considered to be in the range of 400-3200 mg/kg of body weight when rats were treated with 2-tert-butylhydroquinone.

In a study conducted by Sustainability Support Services (Europe) AB (2014) for read across, acute oral toxicity was evaluated in Wistar female rats by using 4,4'-methylenedi-2,6-xylenol in the concentration of 300 and 20000 mg/kg bw in corn oil by acute toxic class method and observed for 14 days. No effect on survival of treated rats was observed as compared to control. Mild to moderate lethargy and ataxia were observed in 300 and 2000 mg/kg bw treated rats. No external and internalgross pathological changes were observed in 2000 mg/kg bw treated rats. Therefore, LD50 was considered to be 5000 mg/kg bw whenWistar female rats were treated with 4,4'-methylenedi-2,6-xylenol orally.

In a study conducted by Sustainability Support Services (Europe) AB (2014) for read across, acute oral toxicity was evaluated in Wistar female rats by using 4,4'-methylenedi-2,6-xylenol in the concentration of 0 and 20000 mg/kg bw in water by acute toxic class method and observed for 14 days. No mortality and clinical sign were observed in treated rats. Increase in body weight on day 7th and 14th (post treatment) were observed in treated rats as compared to control. Skin and hair coat was observed wet in gross pathology as compared to control. Therefore, LD50 was considered to be 2000 mg/kg bw when Wistar female rats were treated with 4,4'-methylenedi-2,6-xylenol orally.

Thus based on above available data for target 1-Naphthalenecarboxaldehyde, 2-hydroxy-, [(2-hydroxy-1-naphthalenyl) methylene] hydrazine (CAS no 2387-03-3) and its structurally related read across 2-tert-butylhydroquinone (CAS no 1948-33-0) and 4, 4'-methylenedi-2, 6-xylenol (CAS no 1948-33-0) as per the CLP regulation is likely to be non hazardous by oral route.

Acute inhalation toxicity:

The chemical 2-hydroxynaphthalene-1-carbaldehyde [Synonym: C.I. Pigment Yellow 101] has a high melting point of 301oC. Thus, it is expected to have low vapour pressure. Therefore, exposure by the inhaltion route by the vapors of this chemical is unlikely. In addition, the particle size distribution of the chemical was found to be in the range of 150 micron to 25 micron which is not of inhalable size. Thus, taking all these aspects into consideration, acute toxicity by the inhalation route is expected to be unlikely. Thus, this end point was considered for waiver since the chemical is not likely to exhibit acute toxicity by the inhalation route.

Acute dermal toxicity:

Based on the prediction done by using QSAR toolbox version 3.3 (2016), acute dermal toxicity was estimated in Fischer 344 male and female rats by using 1-Naphthalenecarboxaldehyde, 2-hydroxy-, [(2-hydroxy-1-naphthalenyl) methylene] hydrazine dermally for 24 hours. The estimated LD50 was found to be 4247.017578125 mg/kg bw when Fischer 344 male and female rats were treated with 1-Naphthalenecarboxaldehyde, 2-hydroxy-, [(2-hydroxy-1-naphthalenyl) methylene] hydrazine dermally for 24 hours.

Based on the above reviewed study for the target 1-Naphthalenecarboxaldehyde, 2-hydroxy-, [(2-hydroxy-1-naphthalenyl) methylene] hydrazine (CAS no 2387-03-3) as per the CLP regulation is likely to be non hazardous by dermal route to rabbits.

Justification for selection of acute toxicity – oral endpoint
Experimental result; Data purchased from BASF

Justification for selection of acute toxicity – inhalation endpoint
The chemical 2-hydroxynaphthalene-1-carbaldehyde [Synonym: C.I. Pigment Yellow 101] has a high melting point of 301oC. Thus, it is expected to have low vapour pressure. Therefore, exposure by the inhaltion route by the vapors of this chemical is unlikely. In addition, the particle size distribution of the chemical was found to be in the range of 150 micron to 25 micron which is not of inhalable size. Thus, taking all these aspects into consideration, acute toxicity by the inhalation route is expected to be unlikely. Thus, this end point was considered for waiver since the chemical is not likely to exhibit acute toxicity by the inhalation route.

Justification for selection of acute toxicity – dermal endpoint
The LD50 value for 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone in F344 rats is estimated to be 4247 mg/kg bw by dermal route of exposure.

Justification for classification or non-classification

The chemical 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone (Yellow 101) was not found to be toxic in acute toxicity study by the oral and dermal route.

Acute inhlation toxicity is also unlikely given the high melting point of this chemical, resulting in low vapour pressure and therefore exposure by the inhalation route will be unlikely. In addition, the particle size distribution of the chemical was found to be in the range of 150 micron to 25 micron which is not of inhalable size. Thus, acute toxicity by the inhalation route is also unlikely

Considering all of the above data, the chemical 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone is not likely to be acute toxic by the oral, inhaalation and dermal route