Reaction products of 2-(chloromethyl)oxirane and glycerol

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD Toolbox 3.0, 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:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-chloro-2,3-epoxypropane

EC Number:

203-439-8

EC Name:

1-chloro-2,3-epoxypropane

Cas Number:

106-89-8

Molecular formula:

C3H5ClO

IUPAC Name:

2-(chloromethyl)oxirane

Test material form:

other: liquid

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:
Epichlorohydrin (CAS 106-89-8): C1(CCl)CO1

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

LOAEL

Effect level:

3.3 mg/kg bw/day (nominal)

Sex:

male/female

Remarks on result:

other: no further information available

Results: F1 generation

Effect levels (F1)

Remarks on result:

other: not predicted with Toolbox

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: LOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression: Result: Out of Domain

("a" and ("b" and "c" ) )

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"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.626

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.626

Applicant's summary and conclusion

Conclusions:

Epychlorohydrin caused reduced male fertility with histopathological changes in the testis and epididymidis and therefore reproductive adverse effects of the target substance cannot be ruled out. However, the read-across substance epichlorohydrin is not classified officially as toxic to reproduction therefore no decision on classification and labelling for reproductive toxicity can be assigned to the target chemical GE-100 based on this data.

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 epichlorohydrin with glycerol. Therefore, epichlorohydrin is considered to be a suitable candidate for read-across. Moreover, its profiling results regarding binding to proteins and to DNA (properties which are likely responsible for reproductive toxicity) are similar to those of the target.

Epichlorohydrin caused reduced male fertility and an increase in the incidence of histopathological changes of the testis and epididymidis and therefore reproductive adverse effects of the target chemical cannot be ruled out as well.