Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
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
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Control animals:
not specified
Dose descriptor:
other: not specified
Based on:
not specified
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
Organ:
not specified
Dose descriptor:
NOAEL
Generation:
F2
Effect level:
243.829 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified

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

(((((("a" and ("b" and ( not "c") )  )  and ("d" and ( not "e") )  )  and "f" )  and "g" )  and "h" )  and ("i" and "j" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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 >> Carbamates OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents 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 >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone (di)imines OR Schiff base formation OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives >> Pyrazolones and pyrazolidinones OR SN2 OR SN2 >> Nucleophilic substitution at Nitrogen atom OR SN2 >> Nucleophilic substitution at Nitrogen atom >> N-halogenated diketones or sulfoxides/sulfones OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides >> Heterocyclic sulfenamides by Protein binding by OASIS v1.1

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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 by Protein binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Similarity boundary:Target: C(=O)(O)c1c(O)ccc(N(=O)=O)c1
Threshold=10%,
Dice(Atom centered fragments)

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.14

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.73

Conclusions:
In Combined Repeated Dose Toxicity Study with the Reproduction Test NOAEL (no observed adverse effect level) of 5-nitrosalicylic acid in female rat by oral (gavage)route was estimated at a dose concentration of 243.8289 mg/kg bw/day.
Executive summary:

In Combined Repeated Dose Toxicity Study with the Reproduction Test NOAEL (no observed adverse effect level) of 5-nitrosalicylic acid in female rat by oral (gavage)route was estimated at a dose concentration of 243.8289 mg/kg bw/day.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
243.829 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The data is K2 level as the data has been obtained from QSAR model considered by OECD.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Toxicity to reproduction

In Combined Repeated Dose Toxicity Study with the Reproduction Test NOAEL (no observed adverse effect level) of 5-nitrosalicylic acid in female rat by oral (gavage)route was estimated at a dose concentration of 243.8289 mg/kg bw/day.

Short description of key information:

5-nitrosalicylic acid does not show any reperotoxic effects in rats.

Justification for selection of Effect on fertility via oral route:

In Combined Repeated Dose Toxicity Study with the Reproduction Test NOAEL (no observed adverse effect level) of 5-nitrosalicylic acid in female rat by oral (gavage)route was estimated at a dose concentration of 243.8289 mg/kg bw/day.

Effects on developmental toxicity

Description of key information

5-nitrosalicylic acid does not show any developmental effects in rats.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
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
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
whole body
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Control animals:
not specified
Dose descriptor:
other: not specified
Based on:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Abnormalities:
not specified
Localisation:
not specified
Description (incidence and severity):
not specified
Dose descriptor:
NOAEL
Effect level:
220.8 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: fetotoxicity
Remarks on result:
other: not specified
Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified
Developmental effects observed:
not specified
Treatment related:
not specified

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

(((((("a" and ("b" and ( not "c") )  )  and ("d" and ( not "e") )  )  and "f" )  and "g" )  and "h" )  and ("i" and "j" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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 >> Carbamates OR Acylation >> Direct acylation involving a leaving group >> N-acylamides 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 conjugated systems with electron withdrawing group >> Cyanoalkenes OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds OR SN2 >> Nucleophilic substitution at Nitrogen atom OR SN2 >> Nucleophilic substitution at Nitrogen atom >> N-halogenated diketones or sulfoxides/sulfones OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides OR SN2 >> Nucleophilic substitution on heterocyclic sulfenamides >> Heterocyclic sulfenamides OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes by Protein binding by OASIS v1.1

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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 by Protein binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Similarity boundary:Target: C(=O)(O)c1c(O)ccc(N(=O)=O)c1
Threshold=20%,
Dice(Atom centered fragments)

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.98

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.67

Conclusions:
The fetotoxicity NOAEL (no observed adverse effect level) of 5-nitrosalicylic acid in rat by oral exposure was observed at a dose concentration of
220.8 mg/kg bw/day.
Executive summary:

The fetotoxicity NOAEL (no observed adverse effect level) of 5-nitrosalicylic acid in rat by oral exposure was observed at a dose concentration of 220.8 mg/kg bw/day

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
220.8 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The data is K2 level as the data has been obtained from QSAR model considered by OECD.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Developmental toxicity / teratogenicity

The fetotoxicity NOAEL (no observed adverse effect level) of 5-nitrosalicylic acid in rat by oral exposure was observed at a dose concentration of 220.8 mg/kg bw/day.

Justification for selection of Effect on developmental toxicity: via oral route:

The fetotoxicity NOAEL (no observed adverse effect level) of 5-nitrosalicylic acid in rat by oral exposure was observed at a dose concentration of

220.8 mg/kg bw/day.

Justification for classification or non-classification

The chemical 5-nitrosalicylic acid does not exhibit toxicity to the reproductive system upto the doses mentioned in the study end points.