Identification of Formaldehyde as the Metabolite Responsible for the Mutagenicity of Methyl Tertiary-Butyl Ether in the Activated Mouse Lymphoma Assay

Mackerer, Carl R.; Angelosanto, Frank A.; Blackburn, Gary R.; Schreiner, Ceinwen A.

doi:10.3181/00379727-212-44023

Cited by 28 publications

(7 citation statements)

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“…This concentration did not cause mutagenic effect. Previous results of MTBE assessment by Ames test (Mackerer et al, 1996;Kado et al, 1998;Williams-Hill et al, 1999) and findings in this study clearly indicate its toxic or lethal but nonmutagenic effect on bacterial cells. To explain the real mechanism of DMSO effect in Ames test is out of the scope of this study.…”

Section: Ames Testsupporting

confidence: 79%

Effect of methyl tert‐butyl ether in standard tests for mutagenicity and environmental toxicity

Vosahlikova

Cajthaml

Demnerova

et al. 2006

Environmental Toxicology

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Methyl tert-butyl ether (MTBE) is a synthetic compound that is used as a technological solution to problems created by air pollution from vehicle emissions. An important source of MTBE in the environment is leakage from underground storage tanks at gasoline stations or accidents during gasoline transport. The aim of this study was to evaluate the risk of MTBE leakage for the environment using the Microtox (Vibrio fischeri) toxicity test, Lactuca sativa seed germination test, and Ames bacterial mutagenicity test with Salmonella typhimurium his(-) strains TA98, TA100, YG1041, and YG1042, using both standard plate and preincubation protocols. The result of Microtox expressed as EC(50) was 33 mg (MTBE)/L. The effect of all tested MTBE concentration (0.05, 0.50, and 1.00% v/v) on Lactuca sativa roots elongation was negative and proved its toxicity. The highest tested concentration of MTBE that could be tested in Ames test was 3 mg (MTBE)/plate, because of cytotoxicity. No mutagenic response was observed at this or lower concentrations in any of the four strains used.

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Section: Ames Testsupporting

confidence: 79%

Effect of methyl tert‐butyl ether in standard tests for mutagenicity and environmental toxicity

Vosahlikova

Cajthaml

Demnerova

et al. 2006

Environmental Toxicology

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“…In contrast with what has been previously suggested (98), a lack of involvement of formaldehyde (metabolic product of MTBE) in the onset of mouse liver tumors has recently been reported (99). In condusion, nongenotoxic hormonally related mechanisms appear to be the most plausible explanation for the development of these tumors, as suggested by the National Research Council (100).…”

Section: Organic Compounds Of Leadcontrasting

confidence: 59%

Potential health effects of gasoline and its constituents: A review of current literature (1990-1997) on toxicological data.

Caprino

Togna

1998

Environ Health Perspect

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We reviewed toxicological studies, both experimental and epidemiological, that appeared in international literature in the period 1990-1997 and included both leaded and unleaded gasolines as well as their components and additives. The aim of this overview was to select, arrange, and present references of scientific papers published during the period under consideration and to summarize the data in order to give a comprehensive picture of the results of toxicological studies performed in laboratory animals (including carcinogenic, teratogenic, or embryotoxic activity), mutagenicity and genotoxic aspects in mammalian and bacterial systems, and epidemiological results obtained in humans in relation to gasoline exposure. This paper draws attention to the inherent difficulties in assessing with precision any potential adverse effects on health, that is, the risk of possible damage to man and his environment from gasoline. The difficulty of risk assessment still exists despite the fact that the studies examined are definitely more technically valid than those of earlier years. The uncertainty in overall risk determination from gasoline exposure also derives from the conflicting results of different studies, from the lack of a correct scientific approach in some studies, from the variable characteristics of the different gasoline mixtures, and from the difficulties of correctly handling potentially confounding variables related to lifestyle (e.g., cigarette smoking, drug use) or to preexisting pathological conditions. In this respect, this paper highlights the need for accurately assessing the conclusive explanations reported in scientific papers so as to avoid the spread of inaccurate or misleading information on gasoline toxicity in nonscientific papers and in mass-media messages.

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“…Both DMP and DBP are probably converted to the corresponding alcohols and further to aldehyde metabolites by S-9. 15 Because acetaldehyde and formaldehyde are mutagenic in the mouse lymphoma assay, 16,17 the aldehyde metabolites of DMP and DBP are most likely the mutagenic forms. The data obtained with 610P are difficult to interpret.…”

Section: Discussionmentioning

confidence: 99%

Results of the l5178y mouse lymphoma assay and the balb/3t3 cellin vitro transformation assay for eight phthalate esters

et al. 2000

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Eight phthalate esters, with alcohol chain lengths of 1–11 carbon atoms and with various degrees of branching, were tested in vitro in the L5178Y mouse lymphoma mammalian cell mutation assay and in the Balb/3T3 cell transformation assay. The tests were performed as part of a voluntary testing agreement between the Chemical Manufacturers Association’s Phthalate Esters Panel and the United States Environmental Protection Agency (US EPA). The esters tested were: dimethyl phthalate (DMP), di‐n‐butyl phthalate (DBP), butyl benzyl phthalate (BBP), di‐{n‐hexyl, n‐octyl, n‐decyl} phthalate (610P), di‐isononyl phthalate (DINP), di‐{heptyl, nonyl, undecyl} phthalate (711P), di‐isodecyl phthalate (DIDP) and di‐undecyl phthalate (DUP). Both DMP and DBP were found to produce significant increases in the mutant frequency in the mouse lymphoma assay in the presence but not in the absence of an Aroclor‐induced rat liver activation system (S‐9). Ester 610P gave equivocal results in the mouse lymphoma assay in the presence and absence of rat liver S‐9. There was no indication of mutagenic potential for any of the other test materials in the mouse lymphoma assay, and none of the test materials increased transformation frequency in the Balb/3T3 cell transformation assay. Aldehyde metabolites of the de‐esterified alcohols are postulated to play a role in the positive results for DMP and DBP. Copyright © 2000 John Wiley & Sons, Ltd.

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Identification of Formaldehyde as the Metabolite Responsible for the Mutagenicity of Methyl Tertiary-Butyl Ether in the Activated Mouse Lymphoma Assay

Cited by 28 publications

References 0 publications

Effect of methyl tert‐butyl ether in standard tests for mutagenicity and environmental toxicity

Effect of methyl tert‐butyl ether in standard tests for mutagenicity and environmental toxicity

Potential health effects of gasoline and its constituents: A review of current literature (1990-1997) on toxicological data.

Results of the l5178y mouse lymphoma assay and the balb/3t3 cellin vitro transformation assay for eight phthalate esters

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