US EPA

42011 

Journal Article 

Genotoxic and/or epigenetic effects of some glycol ethers: Results of different short-term tests 

Elias, Z; Daniere, MC; Marande, AM; Poirot, O; Terzetti, F; Schneider, O 

1996 

0 

Occupational Hygiene
ISSN: 1061-0251 

Gordon & Breach Science Publishers, International Publishers Distributor Langhorne PA 19047-3054 

NIOSH/00234203 

2 

1 (1996) 

187-212 

Short term tests were carried out in order to detect an eventual genotoxic and/or epigenetic effect of glycol ethers. The effects sought, and systems used were: gene mutations at the HPRT locus in the V79 cells: sister chromatid exchanges (SCEs) in the V79 cells and chromosomal aberrations in the V79 cells and human lymphocytes; micronuclei (MN) in polychromatic erythrocytes of mouse bone marrow and in vitro in V79 cells; alteration of the mitotic division apparatus and aneuploidy in V79 cells; morphological transformation (MT) of Syrian hamster embryo (SHE) cells; inhibition of intercellular communication (IC) (metabolic cooperation) between V79 cells. The glycol ethers studied were: (1) the ethylene glycol derivatives monomethyl ether (EGME), monoethyl ether (EGEE) and monobutyl ether (EGBE), as well as their intermediate metabolites the alkoxyacetaldehydes MALD, EALD, BALD, and the corresponding final metabolites, the alkoxyacetic acids MAA, EAA, BAA; (2) the propylene glycol derivatives methyl ether ("small alpha"PGME), monobutyl ether (PnB) and dipropylene glycol monobutyl ether (DPnB). The results of the study show that MALD and BALD, and to a lesser extent EGBE (positive at high concentrations), induced gene mutations. Only the alkoxyacetaldehydes were clearly clastogenic. Also, they were strongly positive inducers of SCEs whereas EGEE, EGBE and "small alpha"PGME were weak-positive at high concentrations. Indirect mechanisms could be implicated in the induction of SCEs by the last three compounds. It has been observed that EGEE, EGBE, and "small alpha"PGME enhanced the clastogenic effect of methyl methanesulfonate. The induction of MN (only in vitro) by the ethylene glycol ethers (at high doses) and their metabolites could be due to their toxic effects on the mitotic apparatus. The alkoxyacetaldehydes were the most effective for induction of cell division aberrations and aneuploidy. The presence of many cells with atypical nuclei also indicated that there were perturbations of the mechanisms regulating cell division. Only MALD induced MT in SHE cells. The inhibition of the IC by EGME, EGEE, EGBE, "small alpha"PGME and DPnB was observed. The overall results led us to conclude that: (I) alkoxyacetaldehydes are the active metabolites in in vitro mammalian cell cultures; (2) the diversity of and potential for genotoxic and/or epigenetic effects varies from one compound to another; (3) a dividing cell population is more exposed to the toxicity of ethylene glycol ethers; (4) co-exposition with other risk factors should also be studied. 

ETHERS; CARCINOGENIC AGENTS; BIOASSAY; PHYSIOLOGICAL RESPONSES, ANIMAL; ALCOHOLS; MUTAGENIC AGENTS; ALDEHYDES