title: A 28-day oral toxicity study of echimidine and lasiocarpine in Wistar rats.
abstract: Pyrrolizidine alkaloids (PAs) are a class of naturally-occurring plant toxins. Echimidine is one of the predominant PAs found in honeys produced in Australia and New Zealand. There is a lack of information on the oral toxicity of echimidine on which to base regulatory decisions concerning the risk to humans of these honeys. This GLP study was conducted to assess the subchronic dietary toxicity of echimidine to rats compared to that of lasiocarpine as a positive control. Wistar rats, 10/sex, were fed diets containing 0, 0.6, 1.2 or 2.5 mg/kg bw echimidine. Positive control groups, 10/sex, were fed diets containing 0.6, 1.2 or 2.5 mg/kg bw lasiocarpine. Neither PA had any effect on survival, food consumption, clinical signs, gross lesions, or histopathology. Consumption of lasiocarpine, but not echimidine, decreased bodyweight gain in males at ≥ 1.2 mg/kg bw, and in females at 2.5 mg/kg bw. Slight alterations in white cell counts and serum ALT concentrations at 2.5 mg/kg bw of both PAs were not clinically significant, had no histological correlates, and were considered to be of equivocal relevance. In conclusion, the subchronic No Observed Adverse Effect Level (NOAEL) for echimidine is 2.5 mg/kg bw/day, whereas, on the basis of a treatment-related decrease in bodyweight gain in males at 1.2 mg/kg bodyweight, the NOAEL for lasiocarpine is 0.6 mg/kg bw/day.
authors.affiliation: Food Standards Australia New Zealand, Level 3, 154 Featherston Street, Wellington 6011, 6143, New Zealand. Electronic address: rosalind.dalefield@foodstandards.govt.nz.
authors.forename: Rosalind R
authors.initials: RR
authors.lastname: Dalefield
authors.affiliation: Food Standards Australia New Zealand, Level 3, 154 Featherston Street, Wellington 6011, 6143, New Zealand. Electronic address: michelle.gosse@foodstandards.govt.nz.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Gosse
authors.affiliation: Food Standards Australia New Zealand, 55 Blackall Street, Barton, ACT 2600, Australia. Electronic address: utz.mueller@foodstandards.gov.au.
authors.forename: Utz
authors.initials: U
authors.lastname: Mueller
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006722:Honey / Q000633:toxicity*; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011763:Pyrrolizidine Alkaloids / Q000008:administration & dosage / Q000633:toxicity*; D017208:Rats, Wistar; D018570:Risk Assessment; D012737:Sex Factors; D013997:Time Factors; D059550:Toxicity Tests, Subchronic / Q000379:methods*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D011763:Pyrrolizidine Alkaloids; C000615871:echimidine; C005136:lasiocarpine
keywords: Echimidine; Lasiocarpine; Pyrrolizidine