2-Propenenitrile, reaction products with 1,3-benzenedimethanamine

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

other: QSAR, read-across

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

The reliability of the predictions is not high due to the lack of sufficient RDT data for the UVCB and its constituents and a scarcity of analogues with available experimental data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Principles of method if other than guideline:

QSAR, read-across

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-Propenenitrile, reaction products with 1,3-benzenedimethanamine

EC Number:

292-054-9

EC Name:

2-Propenenitrile, reaction products with 1,3-benzenedimethanamine

Cas Number:

90530-16-8

IUPAC Name:

2-Propenenitrile, reaction products with 1,3-benzenedimethanamine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

not specified

Results and discussion

Effect levels

1

Dose descriptor:

NOEL

Effect level:

ca. 150 mg/kg bw/day (actual dose received)

Based on:

other:

Sex:

not specified

Basis for effect level:

other: QSAR, read-across

2

Dose descriptor:

LOEL

Effect level:

ca. 342 mg/kg bw/day (actual dose received)

Based on:

other: QSAR, reade-across

Sex:

not specified

Basis for effect level:

other: QSAR, read-across

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The UVCB 2-Propenenitrile, reaction products with 1,3-benzenedimethanamine is not classified as a STOT RE Category 2 H 373 since the reliability of the predictions is not high due to the lack of sufficient RDT data for the UVCB and its constituents and a scarcity of analogues with available experimental data.According to the LOEL predictions, the constituents are Not classified as hazardous for repeated dose toxicity by oral route.

Executive summary:

Ø Experimental NOEL/LOEL data related to the repeated dose toxicity endpoint is found only for m-xylenediamine. The UVCB 2-Propenenitrile, reaction products with 1,3-benzenedimethanamine is not classified as a STOT RE Category 2 H 373 since the reliability of the predictions is not high due to the lack of sufficient RDT data for the UVCB and its constituents and a scarcity of analogues with available experimental data.

Ø The in vivo metabolism of all constituents of theUVCB is taken into account due to the long period of exposure. The presence of nitrile group in some of the metabolites indicates possible toxic effect. Based on this, two general metabolites - β-aminopropionitrile and 3, 3`-Iminodipropionitrile - are examined. Data found in the literature shows that the latter represents neurotoxic substance, whereas prolonged exposure of rats to β-aminopropionitrile may cause osteolathirysm.

Ø Similar structures to the target chemicals are searched in Toolbox databases. No suitable analogues containing all functionalities are found. Therefore the constituents are analyzed based on two functionalities, which are expected to cause toxic effects, i.e. benzylamine and aliphatic nitrile.

Ø The NOEL predictions of constituents A to E, based on the benzylamine functionality, are150 mg/kg bw/d(nominal).

Ø The LOEL predictions of constituents A to E, based on benzylamine and aliphatic nitrile functionalities, exceed the CLP Category 2 threshold. Therefore according to the LOEL predictions, the constituents are Not classified as hazardous for repeated dose toxicity by oral route.