Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt

Endpoint summary

Description of key information

The chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt (Synonym C.I. Food Blue 3) is unlikely to exhibit acute toxicity by the oral and inhalation route of exposure. However, predicted data using the OECD recommended QSAR indicated that it is likely to cause acute dermal toxicity in Category 4.

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:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: Data is from Journal with permission

Principles of method if other than guideline:

The acute toxic effect of Blue VRS was evaluated in mice by a single oral dosage

GLP compliance:

not specified

Test type:

other: No data

Limit test:

yes

Species:

mouse

Strain:

other: Evans

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Carworth Farm E

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

5000 mg/Kg bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not specified

Details on study design:

Details on study design- Duration of observation period following administration: 7 days- Frequency of observations and weighing: No data available- Necropsy of survivors performed: No data available- Other examinations performed: No data available

Statistics:

The LDs0 values with 95% confidence limits calculated according to Litchfield & Wilcoxon (1949).

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No effects on survival and clinical sign

Mortality:

No effect on survival of treated mice were observed.

Clinical signs:

other: No toxic signs were observed in treated mice.

Gross pathology:

No data available

Other findings:

Distinct blue coloration of the skin showed that some of the colouring had been absorbed although substantial amounts were excreted in the faeces.

Interpretation of results:

practically nontoxic

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

LD50 was considered to be > 5000 mg/kg bw when in Evans albino male and female mice were treated with Blue VRS.

Executive summary:

In a acute oral toxicity study, Evans albino male and female mice were treated with VRS orally by gavage. No effect on survival and clinical sign were observed in treated mice. Distinct blue coloration of the skin showed that some of the colouring had been absorbed although substantial amounts were excreted in the faeces. Therefore, LD50 was considered to be > 5000 mg/kg bw when Evans albino male and female mice were treated with Blue VRS orally by gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data from K2 Publication

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from QSAR Toolbox version 3.3

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

The prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: estimation

Species:

rabbit

Strain:

not specified

Sex:

male/female

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 313.588 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" )  and "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and "l" )  )

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 >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Similarity boundary:Target: CCN(CC)c1ccc(C(=C2C=CC(=N{+}(CC)CC)C=C2)c2ccc(S(=O)(=O)O{-})cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Shiff base formation with carbonyl compounds OR AN2 >> Shiff base formation with carbonyl compounds >> Pyrazolone and Pyrazolidine Derivatives OR SN2 OR SN2 >> Nucleophilic ring opening on aziridinium ion intermediate of N-mustards OR SN2 >> Nucleophilic ring opening on aziridinium ion intermediate of N-mustards >> Nitrogen Mustard by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - cyano OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as 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 >> Arenes OR No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -5.64

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.104

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Based on the QSAR prediction done for acute toxicity of hydrogen [4-[4-(diethylamino)-2', 4’-disulphonatobenzhydrylidene] cyclohexa-2, 5-dien-1-ylidene]diethylammonium, sodium salt via dermal route, the LD50 value is estimated to be 1313.5881 mg/kg bw on rabbits. Thus it can be concluded that hydrogen [4-[4-(diethylamino)-2', 4’-disulphonatobenzhydrylidene] cyclohexa-2, 5-dien-1-ylidene]diethylammonium, sodium salt is considered to be cute toxicity category IV as per criteria of CLP regulation.

Executive summary:

Based on the QSAR prediction done for acute toxicity ofhydrogen [4-[4-(diethylamino)-2', 4’-disulphonatobenzhydrylidene] cyclohexa-2, 5-dien-1-ylidene]diethylammonium, sodium saltvia dermal route, the LD50 value is estimated to be 1313.5881 mg/kg bw on rabbits. Thus it can be concluded thathydrogen [4-[4-(diethylamino)-2', 4’-disulphonatobenzhydrylidene] cyclohexa-2, 5-dien-1-ylidene]diethylammonium, sodium saltis considered to be cute toxicity category IV as per criteria of CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 313.588 mg/kg bw

Quality of whole database:

Data is from QSAR Toolbox version 3.3

Additional information

Justification for selection of acute toxicity – oral endpoint

The LD50 with 95% confidence limit of the given test material is found to be >5000 mg/Kg bw.

Justification for selection of acute toxicity – inhalation endpoint

The estimated vapour pressure of the chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt is very low  i.e. 1.145239e-31 Pascal. With such low vapour pressure, exposure by the inhaltion route is highly unlikely. Thus, this end point was considered for waiver.

Justification for selection of acute toxicity – dermal endpoint

Based on the QSAR prediction done for acute toxicity of hydrogen [4-[4-(diethylamino)-2', 4’-disulphonatobenzhydrylidene] cyclohexa-2, 5-dien-1-ylidene]diethylammonium, sodium salt via dermal route, the LD50 value is estimated to be 1313.5881 mg/kg bw on rabbits. Thus it can be concluded that hydrogen [4-[4-(diethylamino)-2', 4’-disulphonatobenzhydrylidene] cyclohexa-2, 5-dien-1-ylidene]diethylammonium, sodium salt is considered to be cute toxicity category IV as per criteria of CLP regulation.