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Description of key information

Based upon the predicted data and avaliable data from authoritative database, for the target chemical (3-oxoglutaric acid) as well as its read across glutaric acid, it can be concluded that in the concentration ranges that are mentioned in the respective end points and also the waivers (given the exposure considerations), the chemicals belonging to the same category of di-carboxylic acid are unlikely to exhibit repeated dose toxicity by the oral, inhalation and dermal route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The target chemical 3-oxoglutaric acid and the read across chemical belong to the same category; that of “dicarboxylic acid”. Both the chemicals share physico-chemical properties within an acceptable range as well as environmental fate properties and aquatic toxicity properties thereby qualifying for suitable read-across. In general, the most striking pattern across the two chemicals is their low toxicity profile.
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Data is from RTECS database
GLP compliance:
not specified
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Duration of treatment / exposure:
90 D
Frequency of treatment:
intermittent
Remarks:
Doses / Concentrations:
135 gm/kg
Basis:
no data
Dose descriptor:
other: TDLo - Lowest published toxic dose
Effect level:
135 other: gm/kg/90D (intermittent)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: Nutritional and Gross Metabolic - weight loss or decreased weight gain
Critical effects observed:
not specified
Conclusions:
Repeated dose toxicity (TDLo - Lowest published toxic dose ) via oral route was examined in rat at dose concentration of 135 gm/kg/90D (intermittent). Thus, it can be concluded that glutaric acid shall not exhibit repeated dose toxicity via the oral route below the concentration mentioned in the end point.
Executive summary:

Repeated dose toxicity (TDLo - Lowest published toxic dose ) via oral route was examined in rat at dose concentration of 135 gm/kg/90D (intermittent). Thus, it can be conlcuded that glutaric acid shall not exhibit repeated dose toxicity via the oral route below the concentration mentioned in the end point.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
chronic
Species:
rat

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 adverse effect observed

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: dermal
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:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
not specified
Duration of treatment / exposure:
21-28 days
No. of animals per sex per dose:
unspecified
Dose descriptor:
NOAEL
Effect level:
671.75 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Critical effects observed:
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 "e" )  )

Domain logical expression index: "a"

Similarity boundary:Target: C(=O)(O)CC(=O)CC(=O)O
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 v1.1

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Schiff base formation OR Schiff base formation >> Nucleophilic cycloaddition to diketones OR Schiff base formation >> Nucleophilic cycloaddition to diketones >> Diketones by Protein binding by OASIS v1.1

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.687

Conclusions:
Repeated dose toxicity NOAEL (No observed adverse effect level) of 3-oxoglutaric acid to rabbit by the dermal route was estimated at a dose concentration of 671.75 mg/kg bw/day.On the basis of this NOAEL value it is concluded that the test substance is not toxic to rabbit by the dermal route below the above mentioned dose.
Executive summary:

Repeated dose toxicity NOAEL (No observed adverse effect level) of 3-oxoglutaric acid to rabbit by the dermal route was estimated at a dose concentration of 671.75 mg/kg bw/day.On the basis of this NOAEL value it is concluded that the test substance is not toxic to rabbit by the dermal route below the above mentioned dose.

In the absence of experimental data for the repeated dose toxicity, the predicted value is considered to be reliable pointer of the low toxicity potential of 3 -oxoglutaric acid. This is also supported by data available in certain literature which indiacte dicarboxylic acid to exhibit low toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
671.75 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Quality of whole database:
In the absence of experimental data for the repeated dose toxicity by the dermal route, the predicted value is considered to be reliable pointer of the low toxicity potential of 3 -oxoglutaric acid. This is also supported by data available in certain literature which indicate dicarboxylic acid to exhibit low toxicity.

Additional information

Based upon the predicted data and avaliable data from authoritative database, for the target chemical (3-oxoglutaric acid) as well as its read across glutaric acid, it can be concluded that in the concentration ranges that are mentioned in the respective end points and also the waivers (given the exposure considerations), the chemicals belonging to the same category of di-carboxylic acid are unlikely to exhibit repeated dose toxicity by the oral, inhalation and dermal route.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Data is from an authoritative database. TDLo - (Lowest published toxic dose ) via oral route was examined in rat at dose concentration of 135 gm/kg/90D (intermittent)

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
Model considered relaible by OECD

Justification for classification or non-classification

Based upon the predicted data and avaliable data from authoritative database, for the target chemical (3-oxoglutaric acid) as well as its read across glutaric acid, it can be concluded that in the concentration ranges that are mentioned in the respective end points and also the waivers (given the exposure considerations), the chemicals belonging to the same category of di-carboxylic acid are unlikely to exhibit repeated dose toxicity by the oral, inhalation and dermal route.

Thus, the chemical 3 -oxoglutaric acid is not classified as exhibiting repeated dose toxicity.