Diisopropyl ether

Endpoint summary

Additional information

In the key bacterial reverse mutation assay (GLP-compliant and equivalent to OECD guideline 471), DIPE was tested at doses of 0, 31.25, 62.5, 125, 250, 500, 1000, 2000, 4000, or 8000 μg/mL in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538 and in Escherichia coli WP2 uvr A pKM 101 both in the presence and absence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Brooks et al., 1985).  Incubations at each concentration were done in triplicate and an independent repeat experiment was performed. A combination of Tween 80 and ethanol was used as the vehicle and positive controls were included in all incubations.  No cytotoxicity and no increase in the reverse mutation rate were observed at any DIPE concentration in any of the tester strains either in the presence or absence of metabolic activation.  Incubation with positive control substances in the presence of metabolic activation resulted in anticipated increases in the reverse mutation rate but did not always do so in the absence of metabolic activation.  This study is therefore considered reliable with restrictions.

 

In a GLP-compliant mammalian chromosome aberration test (equivalent to OECD guideline 473), DIPE was tested at doses of 0, 300, 600, or 1200 µg/mL in rat liver (RL4) cells in the absence of exogenous metabolic activation (Brooks et al., 1985).  Incubations at each concentration were done in triplicate; however, an independent repeat experiment was not performed.  Control incubations were used; however, it is unclear if the control cultures were solvent-treated or untreated. Additionally, 7,12-dimethylbenzanthracene was used as the positive control compound. No cytotoxicity was observed and no chromosome damage was observed at any DIPE concentration.  Incubations with the positive control substance resulted in anticipated increases in chromatid damage.

In the key mammalian gene mutation assay (GLP-compliant and equivalent to OECD guideline 471), DIPE was tested at doses ranging from 50 to 5000 µg/mL for either 3- or 24-hours both in the presence and/or absence of an exogenous metabolic activation system (S9) (Vertesi, 2010). Incubations at each concentration were done in duplicate and an independent repeat experiment was performed. RPMI 5 Medium and DMSO were used as the vehicles and 4-nitroquinoline-N-oxide and cyclophosphamide were used as the positive control compounds in the absence and presence of S9, respectively. No cytotoxicity and no increase in the reverse mutations were observed at any DIPE concentration either in the presence or absence of metabolic activation and incubation with positive control substances resulted in anticipated increases in the reverse mutation rates. 

  

In a GLP-compliant yeast gene mutation assay (equivalent to OECD guideline 480), DIPE was tested at doses of 0, 0.01, 0.1, 0.5, 1.0, or 5.0 mg/mL in Saccharomyces cerevisiae both in the presence and absence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9) (Brooks et al, 1985).  Incubations at each concentration were done in triplicate and an independent repeat experiment was performed. DMSO was used as the vehicle and positive controls were included in all incubations. No cytotoxicity was observed and no increase in the rate of mitotic gene conversion was observed at any DIPE concentration in the presence or absence of metabolic activation. Incubation with positive control substances in the absence (4-nitroquinoline-N-oxide) or presence (cyclophosphamide) of metabolic activation did not always result in anticipated increases in the rate of mitotic gene conversion. Due to this, and as the post-treatment incubation period was 3 days as opposed to the recommended 4 to 7 days, this study is considered reliable with restrictions.

Justification for selection of genetic toxicity endpoint

The four available in vitro studies in its entirety are relevant for the conclusion on mutagenicity; thus, not one of them can be selected per se.

Short description of key information:

The genetic toxicity of diisopropyl ether (DIPE) has been assessed in 4 GLP compliant in vitro studies, including a bacterial reverse mutation assay and a mammalian chromosome aberration test.  Negative results were reported in all studies in the presence and/or absence of metabolic activation.  

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In vitro testing by four different methods produced negative results. As a result, the substance does not meet the criteria for classification for mutagenicity according to Regulation (EC) No 1272/2008, Annex I section 3.5.