3,5-diaminobenzoic acid

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4 with logKow as the primary descriptor.

GLP compliance:

not specified

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): C7H5NO4
- Molecular weight (if other than submission substance): 167.1195 g/mol
- Smiles notation (if other than submission substance): c1(cc(ccc1)[N+](=O)[O-])C(=O)O
- InChI: 1S/C7H5NO4/c9-7(10)5-2-1-3-6(4-5)8(11)12/h1-4H,(H,9,10)
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

21 - 23 °C

pH:

7.5 - 7.9

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

153.057 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

Details on results:

- Exponential growth in the control (for algal test): yes
- Unusual cell shape: No
- Colour differences: No
- Flocculation: No
- Adherence to test vessels: No

The prediction was based on dataset comprised from the following descriptors: EC50
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 ("h" and ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and "r" )  )

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 High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "h"

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: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) sufonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sufonamide group >> Arenesulphonamides OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulphonamides by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "j"

Similarity boundary:Target: Nc1cc(N)cc(C(O)=O)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as 4,4'-Methylenedianilines/benzidines (Hepatobiliary toxicity) Rank B  OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for CA and MNT by OASIS v.1.1

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA alerts for CA and MNT by OASIS v.1.1

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as ECHA PR AND EINECS AND REACH ECB AND TSCA AND US HPV Challenge Program by Inventory Affiliation

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Canada DSL OR DSSTOX OR METI Japan OR NICNAS by Inventory Affiliation

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.8

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.8

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for 3,5-Diaminobenzoic acid on Desmodesmus subspicatus in a 72 hour study was estimated to be 153.05 mg/L on the basis of effects on growth rate.

Executive summary:

The short-term toxicity of the test substance 3,5-Diaminobenzoic acid (CAS no. 535 -87 -5) to  Desmodesmus subspicatus (algae) is predicted using OECD QSAR Toolbox version 3.4 (2017), based on the effects observed in a static freshwater system during a 72 hr exposure. The effect concentration (EC50) for the substance is estimated to be 153.05 mg/L. Based on this value, it can be concluded that the test chemical 3,5-Diaminobenzoic acid can be considered as non-toxic to Desmodesmus subspicatus (algae) at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

Description of key information

The short-term toxicity of the test substance 3,5-Diaminobenzoic acid (CAS no. 535 -87 -5) to  Desmodesmus subspicatus (algae) is predicted using OECD QSAR Toolbox version 3.4 (2017), based on the effects observed in a static freshwater system during a 72 hr exposure. The effect concentration (EC50) for the substance is estimated to be 153.05 mg/L. Based on this value, it can be concluded that the test chemical 3,5-Diaminobenzoic acid can be considered as non-toxic to Desmodesmus subspicatus (algae) at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

153.05 mg/L

Additional information

Various study for the target chemical 3,5-Diaminobenzoic acid (CAS No. 535-87-5) and the study for its read across substancewere reviewed to summarize the following information:

 

The short-term toxicity of the test substance 3,5-Diaminobenzoic acid (CAS no. 535 -87 -5) to  Desmodesmus subspicatus (algae) is predicted using OECD QSAR Toolbox version 3.4 (2017), based on the effects observed in a static freshwater system during a 72 hr exposure. The effect concentration (EC50) for the substance is estimated to be 153.05 mg/L. Based on this value, it can be concluded that the test chemical 3,5-Diaminobenzoic acid can be considered as non-toxic to Desmodesmus subspicatus (algae) at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

The short-term toxicity of the test substance 3,5-Diaminobenzoic acid (CAS no. 535 -87 -5) to algae is predicted using EPI Suite ECOSAR version 1.10(EPI suite, 2017), based on the effects observed in a static freshwater system during a 96 hr exposure. The effect concentration (EC50) for the substance is estimated to be 2886.212 mg/L. Based on this value, it can be concluded that the test chemical 3,5-Diaminobenzoic acid can be considered as non-toxic to algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

In a weight of evidence study of short term toxicity to Pseudokirchneriella subcapitata (green algae) by Po Yi Lee et. al of read across substance 4 -Aminobenzoic acid (CAS no. 150-13-0) which is having a percentage similarity of 50-60% with the target chemical 3,5-Diaminobenzoic acid,was carried out for 48 hrs. The study was performed according to closed system algal toxicity test. The study was based on the effects of the read across compound 4 -Aminobenzoic acid (CAS no. 150-13-0) on Pseudokirchneriella subcapitata (green algae) in a static fresh water system. Algal inoculum was withdrawn from the chemostat operated under a steady state, and transferred into 300mL BOD bottles, together with dilution water (with growth medium) and toxicants. The BOD bottles were filled completely, leaving no headspace. A water seal was provided to ensure a closed test environment. The bottles were then placed on an orbital shaker operated at 100 rpm. Temperature and light intensity were kept at 24±1◦C and 65µEm2/s (± 10%), respectively. The final yield and algal growth rate based on cell density counts was determined. The population density of the algae was determined using an electronic particle counter. Probit analysis was applied to determine the concentration– response relationship and the median effective concentration (EC50). One-tail Dunnett’s procedure was applied for the estimation of NOEC and LOEC values at 5% level of significance. On the basis of effect on growth rate and yield of the test organism Pseudokirchneriella subcapitata (green algae), the 48 hr EC50 value was determined to be 724.4 and 199.9 mg/l, respectively and the NOEC value was determined to be 8.42 mg/l. Thus, based on the EC50 value, it can be concluded that the read across substance 4 -Aminobenzoic acid can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP classification criteria.

 

Another weight of evidence study(J-CHECK, 2016)of short term toxicity to green algae was carried out for 72 hrs for evaluating the effect of the read across substance 3,5 -Xylidine (CAS no. 108 -69 -0) which is having a percentage similarity of 50 -60% with the target chemical 3,5 -Diaminobenzoic acid. The study was based on the effects of the read across compound 3,5 -Xylidine (CAS no. 108 -69 -0) on green algae in a static fresh water system. On the basis of effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be 29 and 5.8 mg/l and on the basis of areas under the growth curves, the 72 hr EC50 and NOEC value was determined to be 22 and 5.8 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 3,5 -Xylidine can be considered as toxic to aquatic organisms and thus can be classified as aquatic chronic category 3. Since the test chemical is readily biodegradable in nature, chemical 3,5 -Xylidine can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP classification criteria.

 

Based on the overall reported results for target and its read across substance, it can be concluded that the test substance 3,5 -Diaminobenzoic acid can be considered as non-toxic to algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria