A repeated dose 90-day oral toxicity study of cyflumetofen,a novel acaricide, in rats

J Toxicol Sci. 2012 Feb;37(1):91-104. doi: 10.2131/jts.37.91.

Abstract

Cyflumetofen is a novel acaricide which is highly active against phytophagous mites. As a part of safety assessment, a repeated dose 90-day oral toxicity study of cyflumetofen was conducted in Fischer (F344/DuCrj) rats of both sexes. Technical grade cyflumetofen was administered in feed to groups of 10 males and 10 females at dose levels of 0, 100, 300, 1,000, and 3,000 ppm. Prothrombin time was prolonged in males at 3,000 ppm and plasma globulin levels were decreased in females at 1,000 and 3,000 ppm. At necropsy, enlarged and whitish adrenals were observed in females at 3,000 ppm. There were statistically significant increases in relative liver weight (ratio to body weight) in males and relative adrenal weight in females in the 1,000 ppm group; increased relative liver and kidney weights in both sexes at 3,000 ppm, and increased absolute and relative weights of adrenals in females at 3,000 ppm. Increased absolute liver weight was also noted in males at 3,000 ppm. Histopathologically, at 1,000 and 3,000 ppm males had diffuse vacuolation and females had diffuse hypertrophy of adrenal cortical cells. In addition, vacuolation of ovarian interstitial gland cells was noted in females at 1,000 and 3,000 ppm. There were no treatment-related changes in any parameters for either sex in other dose groups. Based on these results, the no-observed-adverse-effect level (NOAEL) of cyflumetofen was judged to be 300 ppm for both sexes (16.5 mg/kg/day for males and 19.0 mg/kg/day for females).

MeSH terms

  • Acaricides / toxicity*
  • Adrenal Glands / drug effects
  • Adrenal Glands / pathology
  • Animals
  • Female
  • Kidney / drug effects
  • Kidney / pathology
  • Lipid Metabolism / drug effects
  • Liver / drug effects
  • Liver / pathology
  • Male
  • No-Observed-Adverse-Effect Level
  • Organ Size / drug effects
  • Ovary / drug effects
  • Ovary / pathology
  • Propionates / toxicity*
  • Rats
  • Rats, Inbred F344

Substances

  • Acaricides
  • Propionates
  • cyflumetofen