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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 2.3.
GLP compliance:
no
Test material information:
Composition 1
Species:
other: Rattus norvegicus
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Remarks on result:
not measured/tested
Dose descriptor:
LOEL
Generation:
F2
Effect level:
108.742 other: mg/kg/day
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
Organ:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified

The prediction was based on dataset comprised from the following descriptors: 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" ) and ("g" and ( not "h") ) ) and ("i" and ( not "j") ) ) and ("k" and "l" ) )

Domain logical expression index: "a"

Similarity boundary:Target: C(=O)(O)c1c(C(=O)Nc2ccc(S(=O)(=O)NC3=NC=CS3)cc2)cccc1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Protein Binding Potency

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as 2-Chloroacetamides (SN2) OR 3-Alken-2-ones (MA) OR Alkyl 2-alkenoates (MA) OR Halogenated five membered heterocycles (SN2) OR Halogenated hydrocarbons (SN2) OR Highly reactive (GSH) OR Miscellaneous Alkyl 2-halo alkenoates (SN2) OR Moderately reactive (GSH) OR Non-reactive (GSH) OR Substituted 1-Alken-3-ones (MA) by Protein Binding Potency

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Similarity boundary:Target: C(=O)(O)c1c(C(=O)Nc2ccc(S(=O)(=O)NC3=NC=CS3)cc2)cccc1
Threshold=60%,
Dice(Atom pairs)

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aliphatic tertiary amines OR Arenes OR Aromatic nitro OR MA: Iminium Ion Formation OR MA: Nitrenium Ion Formation OR MA: P450 Mediated Activation to Isocyanates or Isothiocyanates OR MA: P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Mechanistic Domain: Acyalation OR Mechanistic Domain: Michael addition OR Mechanistic Domain: SN1 OR Sulfonylureas by DNA binding by OECD

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.48

Conclusions:
The two generation reproductive toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in Rattus norvegicus was observed at a dose concentration of 108.7419 mg/kg/day.This indicates that phthalylsulfathiazole shall not exhibit toxic effect to Rattus norvegicus below the above mention dose.
Executive summary:

The two generation reproductive toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in Rattus norvegicus was observed at a dose concentration of 108.7419 mg/kg/day.This indicates that phthalylsulfathiazole shall not exhibit toxic effect to Rattus norvegicus below the above mention dose.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
108.742 mg/kg bw/day
Study duration:
subchronic
Species:
other: Rattus norvegicus
Quality of whole database:
K2 data from QSAR model considered relaible by OECD
Additional information

The two generation reproductive toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in Rattus norvegicus was observed at a dose concentration of 108.7419 mg/kg/day.This indicates that phthalylsulfathiazole shall not exhibit toxic effect to Rattus norvegicus below the above mention dose.

Justification for selection of Effect on fertility via oral route:

The two generation reproductive toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in Rattus norvegicus was observed at a dose concentration of 108.7419 mg/kg/day.

Effects on developmental toxicity

Description of key information

The substance phthalylsulfathiazole was found to be non toxic to reproduction.

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:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 2.3.
GLP compliance:
no
Test material information:
Composition 1
Species:
other: Rattus norvegicus
Strain:
not specified
Route of administration:
oral: unspecified
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Remarks on result:
not measured/tested
Dose descriptor:
LOEL
Effect level:
441.95 other: mg/kg/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: LOEL
Estimation method: Taking average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

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

Domain logical expression index: "a"

Similarity boundary:Target: C(=O)(O)c1c(C(=O)Nc2ccc(S(=O)(=O)NC3=NC=CS3)cc2)cccc1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Similarity boundary:Target: C(=O)(O)c1c(C(=O)Nc2ccc(S(=O)(=O)NC3=NC=CS3)cc2)cccc1
Threshold=60%,
Dice(Atom pairs)

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aliphatic halides OR Aliphatic tertiary amines OR Arenes OR Aromatic nitro OR MA: Iminium Ion Formation OR MA: Nitrenium Ion Formation OR MA: P450 Mediated Activation to Isocyanates or Isothiocyanates OR MA: P450 Mediated Activation to Quinones and Quinone-type Chemicals OR MA: SN2 at an sp3 Carbon atom OR Mechanistic Domain: Acyalation OR Mechanistic Domain: Michael addition OR Mechanistic Domain: SN1 OR Mechanistic Domain: SN2 OR Sulfonylureas OR Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.55

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.12

Conclusions:
The fetotoxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in Rattus norvegicus by oral exposure was observed at a dose concentration of 441.9496 mg/kg/day .
Executive summary:

The fetotoxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in Rattus norvegicus by oral exposure was observed at a dose concentration of 441.9496 mg/kg/day . This indicates that phthalylsulfathiazole shall not exhibit toxic effect to Rattus norvegicus by the oral route below the above mention dose.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
441.95 mg/kg bw/day
Study duration:
subchronic
Species:
other: Rattus norvegicus
Quality of whole database:
K2 data from QSAR model considered relaible by OECD
Additional information

The fetotoxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in Rattus norvegicus by oral exposure was observed at a dose concentration of 441.9496 mg/kg/day . This indicates that phthalylsulfathiazole shall not exhibit toxic effect to Rattus norvegicus by the oral route below the above mention dose.

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

The fetotoxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in Rattus norvegicus by oral exposure was observed at a dose concentration of 441.9496 mg/kg/day .

Justification for classification or non-classification

The LOEL values (Lowest observed effect level) of phthalylsulfathiazole on animals indicate that phthalylsulfathiazole shall not exhibit toxic effect to reproduction.