Responses of the L5178Y tk⁺/tk⁻ mouse lymphoma cell forward mutation assay ii: 18 coded chemicals

Abstract

Eighteen chemicals were tested for their mutagenic potential in the L5178Y tk+/- mouse lymphoma cell forward mutation assay by the use of procedures based upon those described by Clive and Spector [Mutat Res 44:269-278, 1975] and Clive et al [Mutat Res 59:61-108, 1979]. Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Significant responses were obtained with benzofuran, benzyl chloride, bromodichloromethane, butylated hydroxytoluene, chlorendic acid, o-chlorobenzalmalonitrile, 1,2,3,4-diepoxybutane, dimethyl formamide, dimethyl hydrogen phosphite, furfural, glutaraldehyde, hydroquinone, 8-hydroxyquinoline, and resorcinol. Apart from bromodichloromethane, butylated hydroxytoluene and dimethyl hydrogen phosphite, rat liver S9 mix was not a requirement for the activity of any of these compounds. Chemicals not identified as mutagens were water, tert-butyl alcohol, pyridine, and witch hazel.

Effects of Glutaraldehyde Exposure on Human Health

“…Both positive and negative results have been reported in in vitro mutagenicity studies [76][77][78][79][80][81][82][83][84][85][86] , while almost all in vivo tests have yielded negative results 75,76,87,88) . GA exhibited mild to strong mutagenic effects with and without S9 metabolic activation in S. typhimurium strain TA102 [77][78][79] .…”

“…SCE and a low frequency of chromosomal aberration were induced by high concentrations of GA, 3.6-16 mg/l, without metabolic activation 75) . Gene mutation was induced by GA in L5178Y tk+/tk-mouse lymphoma cells 85) and the human TK6 lymphoblast cell line 86) . Since GA induced a marginal increase in unscheduled DNA synthesis in the in vitro hepatocyte DNA repair assay (50, 100 µM), DNAreactive genotoxic activity of GA was suggested to involve DNA-protein cross-linking 86) .…”

Butylhydroxytoluol (BHT) [MAK Value Documentation in German language, 2004]

“…Mit S9-Mix ließen sich dagegen in allen drei Untersuchungsreihen, jedoch überwiegend im Bereich hoher Zytotoxizität, Hinweise auf genotoxische Effekte zeigen. DMSO diente in allen Tests als Lösungs-mittel (McGregor et al 1988). Die Kolonien wurden hinsichtlich der Koloniegröße nicht charakterisiert, so dass keine Aussage möglich ist, ob es sich um mutagene oder klastogene Effekte handelte.…”

Scientific opinion on the evaluation of substances as acceptable previous cargoes for edible fats and oils

“…It was also negative in one assay on TA102 with or without metabolic activation (up to 5,000 lg/plate) (McGregor et al, 2005) but was positive in another assay in TA102 in the presence of an exogenous metabolic system at (750 lg/plate) and equivoval in the absence of metabolic activation (Williams-Hill et al, 1999) TBA. It was also negative in a gene mutation assay in mouse lymphoma L5178Y cells at the tk locus up to 5,000 lg/mL (McGregor et al, 1988;NTP, 1997), a chromosomal aberration test in CHO cells up to 5,000 lg/mL (Galloway et al, 1987;NTP, 1997) and a sister chromatid exchange (SCE) test in CHO cells up to 5,000 lg/mL (Galloway et al, 1987;NTP, 1995) in the presence or absence of metabolic activation. A positive result was noted in a Comet assay in human HL-60 leukaemia cells in the absence of metabolic activation at a concentration of 1 mM (Tang et al, 1997).…”