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In vitro tests

The Ames test was performed prior to the adoption of the OECD Guideline 471, but the design of the test method is equivalent to the guideline requirements. In this test, no increasing in revertants was noted in strains TA 1535, TA 1537, TA 1538 and TA 100 with and without metabolic activation. Increasing in revertants was noted only the TA98 strain at three lower dose tested with metabolic activation. The positive result in TA98 is questionable, due to following factors: 1) the number of revertants induced was just at the level chosen for significance (3-fold increase), 2) a 10-fold increase in concentration of test material did not cause a dose-dependent increase in the number or revertants , and 3) higher concentrations of test material that were not toxic (0.1 and 0.3%) did not increase the number of revertants as compared to controls.  On the contrary, the positive control induced a significantly greater number of revertants than the test material. Although the authors of the study concluded that the test material was positive in the assay, the fact that mutagenicity was not noted in other strains with frame shift mutation (TA1537 and TA 1538) along with the issues raised about the positive result with TA strain suggest that this substance does not have the potential to be mutagenic or genotoxic.

In the in vitro mammalian chromosome aberration test using human peripheral blood lymphocytes (HPBL), diallyl diglycol carbonate was concluded to be negative for the induction of structural and numerical chromosome aberrations in the non-activated and S9 activated test systems. The positive and solvent controls fulfilled the requirements for a valid test.

In the Primary Rat Hepatocyte UDS Assay, primary rat hepatocytes obtained from liver of male Fisher 344 rats were exposed to the test substance at concentrations of 0.3313 – 10 nL/mL without metabolic activation for 1 hour and then washed. The test material, CR-39, did not induce detectable UDS in primary rat hepatocytes over an applied concentration range of 10 nL/mL to 0.313 nL/mL. This concentration range caused toxicity ranging from high to nondetectable 20 hours after treatment. Therefore, the test material is considered to be inactive in this assay.

Diallyl diglycol carbonate was tested in the in vitro Mammalian Cell Transformation Assay (Microbiological Associates, 1980b) to investigate the in vitro morphological transforming potential of the test substance in the BALB/3T3 Clone A31 mouse cell line in the absence of an exogenous metabolic activation system. The negative control and the positive control fulfilled the requirements for determination of a valid test. The criterion established for the surviving fraction of cells treated with the test article was also satisfied. The treated 3T3 cells failed to exhibit the morphologically transformed phenotypes designated at Type II and Type III foci at 0.1 µL/mL and 0.03 µL/mL. Under the same test conditions, the cells exposed to a dose of 0.01 µl/ml of test article developed one focus exhibiting the morphologically transformed Type III phenotype among 5.685 x 10E4 cells at risk giving a transformation frequency (TF) of 1.8 x 10E-5. However, relative to the negative control, the induced transformation frequency (TF = 1.8 x 10-5) was not statistically significant (P>0.05).


Short description of key information:
In vitro studies:
1. Ames Test (Microbiological Accociates, 1980), OECD 471;
2. In vitro mammalian Chromosome Aberration Test (BioReliance, 2004), OECD 473;
3. In the Primary Rat Hepatocyte Unscheduled DNA Synthesis Assay (Litton Bionetics, Inc., 1980) OECD 482;
4. In vitro Mammalian Cell Transformation Assay (Microbiological Associates, 1980), EU Method B.21 (In Vitro Mammalian Cell Transformation Test).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

CR 39 (Diallyl diglycol carbonate) does not show the potential for genotoxicity when tested in in vitro bacterial gene mutation assay (Ames Test), Chromosome Aberration Assay, Unscheduled DNA Synthesis Assay and in Mammalian Cell Transformation Assay. There was a questionable response in one strain in Ames Test. However, the fact that mutagenicity was not noted in other strains with frame shift mutation suggests that this substance does not have the potential to be mutagenic or genotoxic.

The classification is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulations No 1272/2008.