Prop-2-yn-1-yl 1H-imidazole-1-carboxylate

Categories

Category name:

Read-across: in Vitro Mammalian Chromosome Aberration Test

Justifications and discussions

Category definition:

in Vitro Mammalian Chromosome Aberration Test

Category description:

log Kow: from -1.71 to 1.35 target chemical is in domain

Category rationale:

REPORTING FORMAT FOR THE CATEGORY APPROACH

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
By using different grouping methods to group chemicals into chemical categories according to different measures of similarity so that within a category a QSAR model can be established. We select profiles related to generic toxicity, including in vitro mutagenicity (Ames test) alerts by ISS, DNA binding by OECD and Protein binding by OECD. Besides, generic toxicity depends on the solubility, shape and reactivity of the chemicals. Therefore, we select "logkow" to describe solubility, Structure similarity to describe the shape of molecule, empiric profiles Toxic hazard classification by Crame to describe the reactivity.

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL
Reliable predicted value obtained by the OECD QSAR Toolbox 4.5 SP1 using Read-across within category members.The prediction fulfilling the OECD criteria for the validation of QSAR models with respect to • a defined endpoint • unambiguous algorithm • a defined domain of applicability • appropriate measure of goodness-of-fit, robustness and predictivity • a mechanistic interpretation.

OECD Principle 1 - Defined endpoint): Human Health Hazards -> Genetic Toxicity -> in Vitro -> in Vitro Mammalian Chromosome Aberration Test -> Chromosome aberration in vitro cytogenicity / chromosome aberration study in mammalian cells -> Chinese hamster Chinese hamster lung fibroblasts (V79) Chinese hamster Ovary (CHO) Human Other Test organisms (species) -> No S9 Info With and Without With S9 Without Without S9 -> Chinese Hamster Lung (CHL) Chinese Hamster Lung Cells Chinese Hamster Lung V-79 Cells Lymphocytes No Strain Information.

OECD principle 2 - Unambiguous algorithm: takes the highest mode value from
the 5 nearest neighbours
Active descriptor: log Kow (calculated)
Data usage: All values*

Database(s) used:
- ECHA REACH
- Genotoxicity & Carcinogenicity ECVAM
- Genotoxicity OASIS
- Genotoxicity pesticides EFSA
- Toxicity Japan MHLW
Category boundaries (applicability domain):
- Active descriptor(s) range:
- log Kow: from -1.71 to 1.35 target chemical is in domain
- Response range:
- in Vitro Mammalian Chromosome Aberration Test: negative (x6); Negative (x10)
Profilers:
- No alert found (in vitro mutagenicity (Ames test) alerts by ISS) (primary grouping) target chemical is in domain
- Structure similarity (subcategorization)
· Mode: Hologram, CombineAllFeatures
· Measure: Dice
· Molecular features: AtomCenteredFragments
· Atom characteristics: AtomType,
CountHAttached, Hybridization
· Differ from target by: At least one category
· Removed categories: [0%,10%); [10%,20%); [20%,30%) target chemical is in domain
- Protein binding by OECD (subcategorization) target chemical is in domain
- DNA binding by OECD (subcategorization) target chemical is in domain
- Toxic hazard classification by Cramer (subcategorization) target chemical is in domain

OECD principle 4 - Uncertainty of the prediction:
The prediction is based on 16 values, 16 of them (100%) equal to predicted value
Prediction confidence is measured by the p-value: 1.53E-05

OECD principle 5 - Chemical and biological mechanisms
No alert found (in vitro mutagenicity (Ames test) alerts by ISS) (primary grouping): No alert found
Structure similarity (subcategorization): [90%,100%]
Protein binding by OECD (subcategorization): No alert found
DNA binding by OECD (subcategorization): No alert found
Toxic hazard classification by Cramer (subcategorization): High (Class III)