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A 28-day oral toxicity study of echimidine and lasiocarpine in Wistar rats
Institution:1. Food Standards Australia New Zealand, Level 3, 154 Featherston Street, Wellington 6011, 6143, New Zealand;2. Food Standards Australia New Zealand, 55 Blackall Street, Barton, ACT 2600, Australia;1. United States Department of Agriculture, Agricultural Research Service, Poisonous Plant Research Lab, Logan, UT, USA;2. Animal Dairy and Veterinary Science Department, Utah State University, Logan, UT, USA;3. School of Veterinary Science, Massey University, Palmerston North, New Zealand;1. College of Physical Science and Technology, Sichuan University, Chengdu 610064, China;2. Institute of Physics, Academia Sinica, Taipei 11529, Taiwan;1. German Federal Institute for Risk Assessment, Max-Dohrn-Straße 8-10, 10589, Berlin, Germany;2. University of Kaiserslautern, Food Chemistry and Toxicology, Erwin-Schrödinger-Straße 52, 67663, Kaiserslautern, Germany
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.
Keywords:Pyrrolizidine  Echimidine  Lasiocarpine  bw"}  {"#name":"keyword"  "$":{"id":"kwrd0030"}  "$$":[{"#name":"text"  "_":"bodyweight  d"}  {"#name":"keyword"  "$":{"id":"kwrd0040"}  "$$":[{"#name":"text"  "_":"day  NOAEL"}  {"#name":"keyword"  "$":{"id":"kwrd0050"}  "$$":[{"#name":"text"  "_":"No Observed Adverse Effect Level  NTP"}  {"#name":"keyword"  "$":{"id":"kwrd0060"}  "$$":[{"#name":"text"  "_":"National Toxicology Program  PA"}  {"#name":"keyword"  "$":{"id":"kwrd0070"}  "$$":[{"#name":"text"  "_":"pyrrolizidine alkaloid  TBHQ"}  {"#name":"keyword"  "$":{"id":"kwrd0080"}  "$$":[{"#name":"text"  "_":"tert-butylhydroquinone
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