Genotoxicity and teratogenicity of diphenyl and diphenyl ether: A study of sea urchins, yeast, andSalmonella typhimurium

Abstract

This study was designed to investigate the possible genotoxic and teratogenic actions of diphenyl (DP), diphenyl ether (DPE), and their eutectic mixture, in a comparative approach including different test systems. Two microbial systems and a metazoan model were used: (1) diploid D7 strain of Saccharomyces cerevisiae; (2) Salmonella typhimurium strains TA100, TA98, TA1535, TA1537, TA1538, TA1532, TA2636; and (3) sea urchins (Paracentrotus lividus and Sphearechinus granularis). Both compounds resulted in severe toxicity in all of test organisms at levels greater than or equal to 10(-5) M (approximately 2 ppm). DP caused genetic effects in yeast with and without activating system, while the two chemicals appeared to be ineffective in Salmonella up to toxic levels. The action of DP and DPE on sea urchins resulted in developmental defects and mitotic abnormalities, following exposure of embryos or by pretreatment of sperm or eggs. In this system DPE appeared to be more effective than DP by about one order of magnitude (minimal active concentrations: 10(-5) M vs 10(-4) M). The eutectic mixture, industrially used as a heat transfer medium, was tested in its virgin and used form, for genotoxicity and embryotoxicity. The latter appeared to be more effective than the virgin eutectic. This increase in the embryo- and genotoxicity of the used eutectic may be related to the appearance of newly formed compounds in the heat transfer process. These compounds have been separated by high-pressure liquid chromatography and detected by fluorimetry.

Scientific Opinion on Flavouring Group Evaluation 78, Revision 1 (FGE.78Rev1): Consideration of aliphatic and alicyclic and aromatic hydrocarbons evaluated by JECFA (63rd meeting) structurally related to aliphatic and aromatic hydrocarbons evaluated by EF

“…1-10 000 μg/plate Negative e (Clark et al, 1979) Reverse mutation S. typhimurium TA98, TA100 (Haworth et al, 1983;NTP, 2004i;NTP, 2004j) Reverse mutation S. typhimurium TA98, TA100, TA1532, TA1535, TA1537, TA1538, TA2636 0.1-500 μg/plate i Negative e (Pagano et al, 1983) Reverse mutation S. typhimurium TA98, TA100, TA2637…”

“…10-5000 μg/plate j Negative e (Nohmi et al, 1985) Reverse mutation S. typhimurium TA97, TA98, TA100 (Pagano et al, 1983) EFSA Journal 2011; 9(6):2178 (Wangenheim and Bolcsfoldi, 1988) Sister chromatid exchange h Slight toxicity was occasionally observed at the highest concentration tested.…”

“…In contrast to the negative results obtained for biphenyl in S. typhimurium and E. coli systems, biphenyl .013] produced genetic effects in an assay with Saccharomyces cerevisiae strain D7, with and without metabolic activation, at concentrations of up to 1 mmol/l (Pagano et al, 1983).…”

Flavouring Group Evaluation 59 (FGE.59): Consideration of aliphatic and aromatic ethers evaluated by JECFA (61st meeting) structurally related to aliphatic, alicyclic and aromatic ethers including anisole derivatives evaluated by EFSA in FGE.23 (2006) (Commission Regulation (EC) No 1565/2000 of 18 July 2000) ‐ Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC)

“…(Florin et al, 1980) Reverse mutation S. typhimurium TA98, TA100, TA1532, TA1535, TA1537, TA1538, TA2636 0.1-500 µg/plate Negative a (Pagano et al, 1983) Reverse mutation S. typhimurium TA100, TA97, TA98, TA102 (Pagano et al, 1983) Reverse mutation S. typhimurium TA100, TA1538, TA98, TA1537, TA1535…”

Biphenyl [MAK Value Documentation in German language, 2001]

“…Nur bei dieser Dosierung war die Körperge-wichtszunahme verringert, außerdem verendeten 5 Muttertiere (Khera et al 1979). Brams et al 1987;Bronzetti et al 1981;Cline und McMahon 1977;Fujita et al 1985;Glatt et al 1992;Haworth et al 1983;Ishidate et al 1984;Kawachi et al 1980;NTP 1980;Pagano et al 1983Pagano et al , 1988Probst et (Sofuni et al 1985) als auch Genmutationen am HPRT-Locus (Glatt et al 1992). Die Induktion der HPRT-Mutationen war nicht von einer nachweisbaren Zytotoxizität der Behandlung begleitet.…”