3,5-diaminobenzoic acid

Endpoint summary

Description of key information

LD50 value was estimated to be 2844 mg/kg bw for rats for 24 duration.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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:

data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached

Reference:

Composition 1

Qualifier:

according to

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: No data

Limit test:

no

Test material information:

Composition 1

Specific details on test material used for the study:

- Name of test material (as cited in study report): 3,5-Diaminobenzoic acid
- Molecular formula (if other than submission substance): C7H8N2O2
- Molecular weight (if other than submission substance): 152.1522 g/mole
- Substance type: Organic
- Physical state: solid

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data

Route of administration:

other: Oral

Vehicle:

not specified

Details on oral exposure:

No data

Doses:

2844 mg/kg bw

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data

Statistics:

No data

Preliminary study:

No data

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 844 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

No data

Clinical signs:

No data

Body weight:

No data

Gross pathology:

No data

Other findings:

No data

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 7 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 ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and "u" )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aminoaniline, meta AND Aniline AND Aryl AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aminoaniline, meta AND Carboxylic acid AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Primary amine AND Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR 4,4'-Methylenedianilines/benzidines (Hepatobiliary toxicity) Rank B  OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Azobenzenes (Hemolytic anemia with methemoglobinemia) Rank B OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Bosentan (Hepatotoxicity) Alert OR Hydrazines (Hepatotoxicity) Rank C OR Methyldopa (Hepatotoxicity) Alert OR Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A OR Nitrobenzenes (Hepatotoxicity) Rank C OR Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B OR o-/ p-Aminophenols (Hemolytic anemia with methemoglobinemia) Rank B OR Organophosphates (Neurotoxicity) Rank A OR Oxyphenistain (Hepatotoxicity) Alert OR p-Aminophenols (Renal toxicity) Rank B OR Phenyl phoshates (Lipodosis of adrenocortial) Rank C OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Aminophenols OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "n"

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 >> N-Carbonylsulfonamides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides 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 >> Michael addition on quinone type chemicals OR Michael Addition >> Michael addition on quinone type chemicals >> Pyranones, Pyridones (and related nitrogen chemicals)  OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Carboxylic Acid Amides OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Nucleoophilic addition to alpha, beta - unsaturated carbonyl compounds OR AN2 >> Nucleoophilic addition to alpha, beta - unsaturated carbonyl compounds >> Propargyl Alcohol Derivatives OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds by Oncologic Primary Classification

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aliphatic Azo and Azoxy Type Compounds OR Arylazo Type Compounds OR Not classified OR Phenol Type Compounds OR Triazene Type Compounds by Oncologic Primary Classification

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Primary aromatic amine, hydroxyl amine and its derived esters by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as 1-phenoxy-benzene OR Aromatic mono- and dialkylamine OR H-acceptor-path3-H-acceptor OR Hydrazine OR Nitro-aromatic OR No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.28

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.962

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2844mg/kg bw for rats for24 duration.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 3,5-diaminobenzoic acid. The LD50 was estimated to be 2844mg/kg bw for rats for24 duration.

.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

2 844 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox version 3.4

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, 3,5-diaminobenzoic acid has been reviewed for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in mice and rats for 3,5-diaminobenzoic acid. The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 3,5-diaminobenzoic acid. The LD50 was estimated to be 2844mg/kg bw for rats for24 duration.

In another study conducted by Schaferet al(Arch. Environ.Contam.Toxicol. 14, 111-129 (1985)), Deer mice were treated with 3,5-diaminobenzoic acid in the concentration of 1250 mg/kg bw orally by gavage using Water, corn oil, 1% carbopol as carriers and observed for 3 days. No 50 % mortality was observed in treated mice at 1250 mg/kg bw. Therefore, LD50 was considered to be > 1250 mg/kg bw when Deer mice were treated with 3,5-diaminobenzoic acid orally by gavage.

Also it is supported by QSAR prediction done using the Danish (Q) SAR Database (2016), the LD50 was estimated to be 2200 mg/kg/day on Rat and 4000 mg/kg/day on mice for substance 3, 5-Diaminobenzoic acid. Thus based on this value it can be concluded that the substance 3, 5-Diaminobenzoic acid can be not classified by oral route as per the criteria of CLP regulation.

Thought, the value of 1250 mg/kg bw was available for target 3, 5-diaminobenzoic acid (CAS no 535875), other predicted data vales are > 2000 mg/kg bw.

Thus, based on the above studies and predictions on 3, 5-diaminobenzoic acid and by applying weight of evidence, it can be concluded that LD50 value is > 2000 mg/kg bw. Thus comparing this value with the criteria of CLP regulation, 3, 5-diaminobenzoic acid can be classified as non toxic for acute oral toxicity.

Justification for classification or non-classification

Based on the above available data for target 3, 5-diaminobenzoic acid (CAS no 535875) is likely to be non hazardous by acute oral route of exposure and hence not classified as per the criteria of CLP regulation.