Reaction products of 2-(chloromethyl)oxirane and glycerol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD Toolbox 3.1, is a harmonized system for OSAR application and grouping chemicals into categories, which OECD principles are met.

Data source

Reference

Reference Type:

other: prediction by the OECD QSAR Toolbox

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

Category members were tested according to the different guidelines

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2,3-epoxypropan-1-ol

EC Number:

209-128-3

EC Name:

2,3-epoxypropan-1-ol

Cas Number:

556-52-5

Molecular formula:

C3H6O2

IUPAC Name:

oxiran-2-ylmethanol

Details on test material:

Target substance:
Mixture of 1,2,3-Propanetriol, polymer with 2-(chloromethyl)oxirane (CAS 25038-044-4) and 1,2,3-Propanetriol, glycidyl ethers:
SMILES:C(O)(CO)CO_C1(CCl)CO1_C1(COC(COCC2CO2)COCC2CO2)CO1

Read-across substances are lited in the Toolbox generated report

Test animals

Species:

other: Mouse;Rat

Administration / exposure

Route of administration:

other: "MM B6C3F1, Gavage (TB:Neg);";"RM Lewis, IP (TB:ND);";"MM B6C3F1, IP (TB:Pos);";"MM B6C3F1, IP (TB:PosHD);";"RM SPRAGUE-DAWLEY, IP (TB:ND);";"MM BALB/C, IP Reticulocytes (TB:ND);";"MM (102XC3H)F1, IP (TB:ND); RM LEWIS, IP (TB:ND);"

Results and discussion

Test results

Sex:

not specified

Genotoxicity:

positive

Toxicity:

not specified

Remarks on result:

other: see "any other information on results incl. tables"

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: "Chromosome aberration"
Estimation method: Takes highest mode 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"

Referential boundary: The target chemical should be classified as Epoxides by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol AND Alkyl halide AND Dihydroxyl group AND Epoxide AND Ether AND Glycerol and derivatives AND Saturated heterocyclic fragment by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkane, branched with tertiary carbon OR Alkene OR Allyl OR Aryl OR Carboxamide OR Carboxylic acid OR Carboxylic acid ester OR Conjugated system OR Cycloalkane OR Fused saturated heterocycles by Organic functional groups

Domain logical expression index: "d"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.09

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.628

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive
The target chemical possesses three epoxide rings at the terminal position which are likely high reactive and can react with DNA molecule, inducing mutations etc. Based on the fact that most of the epoxy compounds (especially low molecular weight chemicals) are mutagenic or clastogenic in genetic toxicity tests, the target substance is considered to have genetic toxicity potential too.

Executive summary:

The target chemical was profiled as "Epoxides" by the "US EPA New Chemical Categories". Common properties of epoxides are high reactivity, cytotoxicity, and high probability of mutagenic potential and/or carcinogenicity. Therefore chemicals with the same profiling result have been retrieved from the database. The chemicals containing other chemical elements in their structure and/or other organic functional groups were considered dissimilar to the target chemical and have been removed from the domain. The target chemical is obtained by the reaction of epychlorohydrin with glycerol. Therefore, epichlorohydrin is considered to be a suitable candidate for read-across. Glycidol is the simplest representative of glycidyl ethers category (HPV, Epoxy Resin Systems Task Group (ERSTG), 2001). The other category members possess epoxy moieties in their structures and their profiling results regarding the ability to bind to proteins and to DNA (property which is likely responsible for genetic toxicity) are similar to those of the target chemical. Therefore, they considered to be suitable for read-across. The target substance was predicted to be positive in in vivo Micronucleus Test.