3-acetamido-5-amino-4-hydroxybenzenesulphonic acid

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3.

GLP compliance:

no

Species:

rat

Strain:

other: F344;F344/N;Fischer;Wistar;Sprague-Dawley;ChR COBS-CD;SD-JCL;Sherman

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Dose descriptor:

LOEL

Effect level:

895.442 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

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

((("a" and ("b" and ( not "c") ) ) and "d" ) and ("e" and "f" ) )

Domain logical expression index: "a"

Similarity boundary:Target: c1(N)c(O)c(NC(C)=O)cc(S(=O)(=O)O)c1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid anhydride OR Activated alkyl esters OR alpha,beta-carbonyl compounds with polarized double bonds OR MA: Direct acylation involving a leaving group OR MA: Michael addition on conjugated systems with electron withdrawing group OR MA: Nucleophilic substitution at sp3 Carbon atom OR Mechanistic Domain: Acylation OR Mechanistic Domain: Michael addition OR Mechanistic Domain: SN2 OR N-acylamides OR N-acylsulphonamides OR Nitroalkenes OR Thiophosphates by Protein binding by OASIS

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.81

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.273

Conclusions:

The repeated dose toxicity LOEL (Lowest observed effect level) of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid in rat was observed at a dose concentration of 895.4425 mg/kg/day by the oral route.This indicates that 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid shall not exhibit toxic effect to rat by the oral route below the above mention dose.

Executive summary:

Based on the QSAR estimation, the repeated dose toxicity LOEL (Lowest observed effect level) of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid in rat was observed at a dose concentration of 895.4425 mg/kg/day by the oral route.This indicates that 3-acetamido-5-amino-4-hydroxy benzene sulphonic acid shall not exhibit toxic effect to rat by the oral route below the above mention dose.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

895.442 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

K2 data from QSAR model considered reliable by OECD

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity for all the route for toxicity

Repeated dose toxicity : Oral

The repeated dose toxicity LOEL (Lowest observed effect level) of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid in rat was observed at a dose concentration of 895.4425 mg/kg/day by the oral route.This indicates that 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid shall not exhibit toxic effect to rat by the oral route below the above mention dose.

Repeated dose toxicity : Inhalation

In accordance with column 2 of Annex VIII, this end point was considered for waiver since given the very low vapour pressure of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid; exposure of humans via inhalation is highly unlikely and their is negligible possibility of exposure to aerosols, particles or droplets of an inhalable size.

Repeated dose toxicity : Dermal

There are studies that indicate the acute dermal toxicity (LD50) of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid on rat was obtained to be more than 2000 mg/kg body weight. Also, this chemical do not have skin sensitization. Moreover, dermal route of exposure is not the most dominant route when considering the intermediate use of this substance. In view of all the above, this end point was considered for waiver

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The repeated dose toxicity LOEL (Lowest observed effect level) of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid in rat was observed at a dose concentration of 895.4425 mg/kg/day by the oral route.This indicates that 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid shall not exhibit toxic effect to rat by the oral route below the above mention dose.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

In accordance with column 2 of Annex VIII, this end point was considered for waiver since given the very low vapour pressure of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid; exposure of humans via inhalation is highly unlikely and their is negligible possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

There are studies that indicate the acute dermal toxicity (LD50) of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid on rat was obtained to be more than 2000 mg/kg body weight. Also, this chemical do not have skin sensitization. Moreover, dermal route of exposure is not the most dominant route when considering the intermediate use of this substance. In view of all the above, this end point was considered for waiver

Justification for classification or non-classification

The available studies indicate that 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid is not classified as a repeated dose toxicity for any of the route of exposure as per the C&L classification.