کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5846729 | 1128503 | 2012 | 8 صفحه PDF | دانلود رایگان |
The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6Â mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4-10.9Â mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28Â days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360Â ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120Â ppm, versus 229Â ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60Â ppm dose and in one female rat at the 30Â ppm dose, establishing a NOAEL of 2.1Â mg/kg bw/day for males and <Â 2.6Â mg/kg bw/day for females, and BMDL values as low as 1.6Â mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid.
⺠A 28-day dietary co-exposure to melamine and cyanuric acid was conducted in F344 rats. ⺠The NOAELs were 2.1 mg/kg bw/day for males and < 2.6 mg/kg bw/day for females. ⺠BMDL values as low as 1.6 mg/kg bw/day for both sexes were determined. ⺠The length of exposure plays an important role in the threshold of toxicity. ⺠Current assessments may underestimate the risk of melamine and cyanuric acid.
Journal: Toxicology and Applied Pharmacology - Volume 262, Issue 2, 15 July 2012, Pages 99-106