title: A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats.
abstract: 3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester: CDP, palmitate monoester: CMP, oleate diester: CDO). We administered a carcinogenic dose (3.6 × 10(-4) mol/kg B.W./day) of 3-MCPD or these esters at equimolar concentrations and two 1/4 lower doses by gavage with olive oil as a vehicle five times a week for 13 weeks to F344 male and female rats. As a result, five out of ten 3-MCPD-treated females died from acute renal tubular necrosis, but none of the ester-treated rats. Decreased HGB was observed in all high-dose 3-MCPD fatty acid ester-treated rats, except CDO-treated males. The absolute and relative kidney weights were significantly increased in the ester-treated rats at medium and high doses. Relative liver weights were significantly increased in the esters-treated rat at high dose, except for CMP females. Significant increase in apoptotic epithelial cells in the initial segment of the epididymis of high-dose ester-treated males was also observed. The results suggested that although acute renal toxicity was lower than 3-MCPD, these three 3-MCPD fatty acid esters have the potential to exert subchronic toxicity to the rat kidneys and epididymis, to a similar degree as 3-MCPD under the present conditions. NOAELs (no-observed-adverse-effect levels) of CDP, CMP and CDO were suggested to be 14, 8 and 15 mg/kg B.W./day, respectively.
authors.affiliation: Pathology, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Onami
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Cho
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyoda
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mizuta
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D004952:Esters / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007673:Kidney Cortex Necrosis / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009829:Oleic Acids / Q000633:toxicity*; D009929:Organ Size; D010169:Palmitic Acids / Q000633:toxicity*; D011916:Rats, Inbred F344; D013997:Time Factors; D059550:Toxicity Tests, Subchronic; D000517:alpha-Chlorohydrin / Q000031:analogs & derivatives / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D004952:Esters; D009829:Oleic Acids; D010169:Palmitic Acids; D000517:alpha-Chlorohydrin