Evaluation of the safety of mixed tocopheryl phosphates (MTP) -- a formulation of alpha-tocopheryl phosphate plus alpha-di-tocopheryl phosphate.
The safety of a formulation of mixed tocopheryl phosphates, (MTP) was evaluated in a series of toxicological tests in vivo using rats, mice and rabbits and in vitro using bacterial and mammalian cell cultures. The tests conducted included an oral LD(50) study, three 28-day oral repeat-dose studies, two dermal toxicity tests, an ocular irritation test, mutagenic potential tests, and chromosomal aberrations tests. MTP consists of mono alpha-tocopheryl phosphate (TP) and di-tocopheryl phosphate (T(2)P) and is intended for use as a dietary supplement and for dermal applications in humans and animals. The dermal and oral LD(50) values of MTP were determined to be >1130 mg/kg bw (918 mg tocopherol equivalents/kg bw) in rabbits and rats, respectively. MTP was not a dermal or eye irritant in rabbits and showed no allergenic potential in mice. In the mutagenicity and genotoxicity studies, MTP did not increased the number of revertants in Salmonella typhimurium or Escherichia coli and did not induce chromosomal aberrations in cultured Chinese hamster ovary (CHO) cells. When administered daily for 28 days by gavage at doses up to 955 mg/kg bw/day (780 mg tocopherol equivalents/kg bw/day), MTP produced no consistent, dose-dependent adverse effects in rats.
Libinaki
R
R
Department of Biochemistry and Molecular Biology, Monash University, Building 13D, Melbourne 3800, Australia.
Ogru
E
E
Gianello
R
R
Bolton
L
L
Geytenbeek
S
S
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000633:toxicity*; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects; D003872:Dermatitis / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005128:Eye Diseases / Q000139:chemically induced; D005260:Female; D006967:Hypersensitivity / Q000473:pathology; D007509:Irritants; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009152:Mutagenicity Tests; D009153:Mutagens; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity
D000975:Antioxidants; D007509:Irritants; D009153:Mutagens; C512375:alpha-di-tocopheryl phosphate; C012552:alpha-tocopherol phosphate; D024502:alpha-Tocopherol