Tests for mutagenic effects of ammoniated glycyrrhizin, butylated hydroxytoluene, and gum arabic in rodent germ cells

Abstract

Ammoniated glycyrrhizin, butylated hydroxytoluene, and gum Arabic are "generally recognized as safe" (GRAS) substances that are used primarily as additives in foods. These substances were incorporated into rodent diets and fed to male rats and mice for 10 and 8 wk, respectively. The treated male mice and rats were then tested for dominant lethal effects. The mice were also tested for induced heritable translocation. Results of the rat studies indicated a statistically significant dominant lethal effect of each of the compounds tested; however, the biological significance of this response is not known. Results of the mouse dominant lethal and heritable translocation studies, on the other hand, indicated no adverse effects of the compounds tested.

Scientific Opinion on the safety and efficacy of glycyrrhizic acid ammoniated (chemical group 30, miscellaneous substances) when used as a flavouring for all animal species

“…In a mouse dominant-lethal test (Sheu et al, 1986), groups of 36 male mice ((101  C57BL)F 1 strain) were fed diets containing 0 (control) or 2.25 % (w/w) ammoniated glycyrrhyzin for eight weeks. They were then mated with (SEC  C57BL)F 1 strain and (C3H  C57BL)F 1 strain female mice.…”

“…Examination of numbers of live and dead implantations showed no increase in the number of dominant-lethal mutations in the offspring. Sheu et al (1986) also performed a dominant-lethal test in rats. Groups of 20 male Sprague-Dawley rats that had been given diets containing 0 (vehicle control), 0.4, 1.3 or 4.0 % (w/w) ammoniated glycyrrhizin for 10 weeks were mated with untreated females at one and two weeks post treatment.…”

“…Following on from the dominant-lethal test in mice, the offspring were grown to adulthood and a heritable translocation test was performed on them (Sheu et al, 1986). A total of 463 control and 507 experimental male progeny were tested for fertility.…”

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

“…Mutationstests an Keimzellen Dominant-Letal-Tests an Mäusen (Epstein und Shafner 1968;Epstein et al 1972;Sheu et al 1986;Masubuchi et al 1976) und Ratten (FDA 1972Maxwell und Newell 1974) lieferten keine Hinweise auf eine Induktion von Dominant-Letal-Mutationen durch BHT. Bei einer Studie an Sprague-Dawley-Ratten (FDA 1977;Sheu et al 1986), für die bei einer ersten Auswertung ein nicht-dosisabhängiger Anstieg der Zahl toter Implantate innerhalb der ersten Behandlungswoche ermittelt worden war, ergab die erneute Auswertung nach neueren Richtlinien wie in allen übrigen Studien keinen Hinweis auf mutagene Wirkungen von BHT (Bruce und Heddle 1979).…”

“…Bei einer Studie an Sprague-Dawley-Ratten (FDA 1977;Sheu et al 1986), für die bei einer ersten Auswertung ein nicht-dosisabhängiger Anstieg der Zahl toter Implantate innerhalb der ersten Behandlungswoche ermittelt worden war, ergab die erneute Auswertung nach neueren Richtlinien wie in allen übrigen Studien keinen Hinweis auf mutagene Wirkungen von BHT (Bruce und Heddle 1979). BHT induzierte in Mäusen auch keine erblichen Translokationen (Sheu et al 1986) oder spezifischen Locusmutationen (Cumming et al 1976). …”