title: Comparison of the toxicity of citral in F344 rats and B6C3F1 mice when administrated by microencapsulation in feed or by corn-oil gavage.
abstract: A study of the potential effects of microencapsulation on the toxicity of citral was conducted in 14-day continuous feeding studies with both sexes of F344 rats and B6C3F1 mice. Toxicity by the feeding route was compared with that from bolus doses of the neat chemical in corn oil administrated by gavage. Both sexes of rats and mice were given diet containing 0, 0.63, 1.25, 2.5, 5 and 10% citral microcapsules. These feed formulations were equivalent to daily doses of 0, 142, 285, 570, 1140 and 2280 mg citral/kg body weight for rats and 0, 534, 1068, 2137, 4275 and 8550 mg citral/kg body weight for mice. The daily gavage doses were 0, 570, 1140 and 2280 mg citral/kg body weight for both sexes of rats, and 0, 534, 1068 and 2137 mg citral/kg body weight for both sexes of mice. Citral microcapsules administered in the diet did not cause mortality in mice or rats. Toxicity was confined to decreases in body weight at the 10% concentration in mice, at the 5 and 10% concentrations in rats, and decreases in absolute weights of the liver, kidney and spleen at the 10% concentration in rats. The only histopathological change observed was minimal to mild hyperplasia and/or squamous metaplasia of the respiratory epithelium in the anterior portion of the nasal passages of rats fed 5 or 10% citral microcapsules. By contrast, citral gavage caused mortality in five out of five male and female mice at 2137 mg/kg body weight, and in two out of five male mice at 1068 mg/kg body weight. There were dose-related increases in absolute liver weights of male and female mice. Cytoplasmic vacuolization of hepatocytes occurred in all female mice gavaged with 1068 and 2137 mg citral/kg body weight, and in male mice from the 2137 mg/kg dose group. Necrosis, ulceration and/or acute inflammation of the forestomach occurred in the high-dose mice of both sexes. Inflammation and/or hyperplasia of the forestomach occurred in about half of the male and female mice dosed with 1068 mg citral/kg. Citral gavage at doses that were equivalent to up to 10% in the diet (2280 mg/kg body weight) did not cause toxicity in rats, except for minimal hyperplasia of the squamous epithelium of the forestomach in high-dose males.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
authors.forename: M P
authors.initials: MP
authors.lastname: Dieter
authors.forename: T J
authors.initials: TJ
authors.lastname: Goehl
authors.forename: C W
authors.initials: CW
authors.lastname: Jameson
authors.forename: M R
authors.initials: MR
authors.lastname: Elwell
authors.forename: P K
authors.initials: PK
authors.lastname: Hildebrandt
authors.forename: J H
authors.initials: JH
authors.lastname: Yuan
mesh_terms: D000080462:Acyclic Monoterpenes; D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003314:Corn Oil; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004339:Drug Compounding; D004435:Eating / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D039821:Monoterpenes; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013729:Terpenes / Q000008:administration & dosage* / Q000633:toxicity*; D014116:Toxicology / Q000379:methods; D014801:Vitamin A / Q000037:antagonists & inhibitors
chemical_list: D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D013729:Terpenes; D014801:Vitamin A; D003314:Corn Oil; C007076:citral