title: Synthesis and mutagenicity of selectively methylated analogs of tris(2,3-dibromopropyl)phosphate and 1,2-dibromo-3-chloropropane.
abstract: Five selectively methylated analogs of the flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) and of the nematocide 1,2-dibromo-3-chloropropane (DBCP) were synthesized and their relative mutagenicities determined in Salmonella typhimurium TA100 in the presence of rat liver microsomes. In all cases, methylation decreased mutagenicity relative to the parent compound, but the relative degree of reduced mutagenicity varied considerably depending on the position of the methyl substitution. The mutagenicity studies with the selectively methylated analogs and with suspected mutagenic metabolites (2-bromocrotonaldehyde and methyl 1-dibromovinyl ketone) supported earlier work with selectively deuterated analogs of Tris-BP and DBCP. They demonstrated that initial oxidation at C-3, followed by spontaneous dehydrohalogenation and dehydrophosphorylation, was the major route of formation of mutagenic metabolites from Tris-BP. In the case of DBCP, formation of mutagenic metabolites can result following initial oxidation at either C-1 or C-3.
authors.affiliation: Department of Toxicology, National Institute of Public Health, Oslo, Norway.
authors.forename: J G
authors.initials: JG
authors.lastname: Omichinski
authors.forename: E J
authors.initials: EJ
authors.lastname: Søderlund
authors.forename: J A
authors.initials: JA
authors.lastname: Bausano
authors.forename: E
authors.initials: E
authors.lastname: Dybing
authors.forename: S D
authors.initials: SD
authors.lastname: Nelson
mesh_terms: D000818:Animals; D001711:Biotransformation; D005411:Flame Retardants / Q000494:pharmacology; D007306:Insecticides; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000138:chemical synthesis*; D009154:Mutation; D010755:Organophosphates / Q000138:chemical synthesis* / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D005411:Flame Retardants; D007306:Insecticides; D009153:Mutagens; D010755:Organophosphates; D009943:Organophosphorus Compounds; C012085:tris(2,3-dibromopropyl)phosphate; C007318:1,2-dibromo-3-chloropropane; D011407:Propane