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Description of key information

The substance phthalylsulfathiazole is not toxic by oral and inhalation route through repeated dose.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
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:
rat
Strain:
Sprague-Dawley
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Dose descriptor:
LOEL
Effect level:
386.755 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
Organ:
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 "c" ) and ("d" and "e" ) )

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 High (Class III) by Toxic hazard classification by Cramer (original)

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.41

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.06

Conclusions:
Repeated dose toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in rat (Sprague-Dawley) by the oral route was estimated at a dose concentration of 386.7549 mg/kg/day.
Executive summary:

Repeated dose toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in rat (Sprague-Dawley) by the oral route was estimated at a dose concentration of 386.7549 mg/kg/day.On the basis of this LOEL value it is concluded that the test substance is not toxic to rat (Sprague-Dawley) by oral route below the above mentioned dose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
386.755 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
K2 data from QSAR model considered relaible by OECD

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
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:
rat
Strain:
Sprague-Dawley
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Dose descriptor:
LOEL
Effect level:
106.227 mg/kg bw/day (actual dose received)
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
Organ:
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 "c" ) )

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"

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

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.85

Conclusions:
Repeated dose toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole to rat (Sprague-Dawley)by the inhalation route was estimated at a dose concentration of 106.2268 mg/kg/day.
Executive summary:

Repeated dose toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole to rat (Sprague-Dawley)by the inhalation route was estimated at a dose concentration of 106.2268 mg/kg/day. On the basis of this LOEL value it is concluded that the substance phthalylsulfathiazole is not toxic to rat (Sprague-Dawley) by inhalative route below the above mentioned dose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
106.227
Study duration:
subchronic
Species:
rat
Quality of whole database:
K2 data from QSAR model considered relaible by OECD

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

Additional information

Repeated dose toxicity :

Repeated dose toxicity : Oral

Repeated dose toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in rat (Sprague-Dawley) by the oral route was estimated at a dose concentration of 386.7549 mg/kg/day.On the basis of this LOEL value it is concluded that the test substance is not toxic to rat (Sprague- Dawley)by oral route below the above mentioned dose. The supporting studies showes TDLo - Lowest published toxic dose values for phthalylsulfathiazole also support the key study indicating non toxic behaviour of the substance.

Repeated dose toxicity : Inhalation

Repeated dose toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole to rat (Sprague-Dawley)by the inhalation route was estimated at a dose concentration of 106.2268 mg/kg/day.On the basis of this LOEL value it is concluded that the substance phthalylsulfathiazole is not toxic to rat (Sprague-Dawley) by inhalative route below the above mentioned dose.

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

Repeated dose toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole in rat (Sprague-Dawley) by the oral route was estimated at a dose concentration of 386.7549 mg/kg/day.On the basis of this LOEL value it is concluded that the test substance is not toxic to rat (Sprague-Dawley)by oral route below the above mentioned dose.

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

Repeated dose toxicity LOEL (Lowest observed effect level) of phthalylsulfathiazole to rat (Sprague-Dawley)by the inhalation route was estimated at a dose concentration of 106.2268 mg/kg/day.On the basis of this LOEL value it is concluded that the substance phthalylsulfathiazole is not toxic to rat (Sprague-Dawley) by inhalative route below the above mentioned dose.

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

There are studies that indicate the acute dermal toxicity (LD50) of phthalylsulfathiazole on rat to be greater than 2000 mg/kg body weight. Also, this chemical does not show skin sensitization. Thus indicating that the substance will have negligible effect on dermal exposure and thus is not considered for furhter testing.

Justification for classification or non-classification

On the basis of this LOEL value it is concluded that the substance phthalylsulfathiazole is not toxic via inhalation and oral route. Also demal toxicity will be not considerd as acute toxicity is nil.