Pesticide residues in food — 2006: Toxicological ... - ipcs inchem

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peaks Q3, Q6 and Q14, while peaks Q1 and Q2 were increased after acid hydrolysis. In rats receiving
a single dose at 500 mg/kg bw, peak Q14 was increased in males. Concomitantly, peaks Q4, Q5, Q7,
Q8 and Q10 were observed to disappear from the respective radiochromatograms, while Q3 and Q9
were markedly reduced. Enzyme hydrolysis did not affect the metabolite profile.
HPLC separation of bile samples (taken at various time-points, 0–24 h) from male rats receiving
quinoline ring-labelled quinoxyfen at 10 mg/kg bw or 500 mg/kg bw produced six peaks (B2–B7).
Peaks B6 and B7 constituted 20–66% and 26–59% of biliary excretion at various time-points. For
the 10 mg/kg bw rats, the amount of radiolabel in the peaks at various time-points were B2 6–15%;
B5 4–15%; B3 and B4 < 5%. Only peaks B6 and B7 were detected in the samples from rats at
500 mg/kg bw, but this was attributed to the higher detection limits required by the investigating
laboratory. Additional peaks B1, B8, B9 and B10 were detected after enzyme hydrolysis. Peak B7
was noted to disappear with the appearance of peak B10 (approximately 25%) suggesting that B7 is
the glucuronide or sulfatase of B10. Acid hydrolysis of the bile samples from rats at 10 or 500 mg/kg
bw resulted in an increase in B6 by 20% of the biliary radioactivity compared with the control. Peaks
B1, B8 and B9 appeared in the sample from rats at 10 mg/kg bw, but were not detected at 500 mg/kg
bw. B10 eluted with quinoxyfen, but MS showed that the key ions were 16 mass units greater than
the corresponding fragment ions from quinoxyfen. It was concluded that two metabolites associated
with peak B10 were isomers of fluorophenyl-ring hydroxylated quinoxyfen.
Faecal samples exhibited incomplete extraction, typically < 65%. At 500 mg/kg bw, the main
faecal metabolite was F8, which co-eluted with quinoxyfen. The primary faecal metabolite at
10 mg/kg bw was F6 which was shown to consist of two hydroxylated isomers, equivalent to the
bile metabolite B10. The pattern of metabolites in faeces was essentially independent of radiolabel
position (Schumann et al., 1995)
In a GLP-compliant study conducted in 2001, a group of four male Fischer F344 rats received
quinoxyfen (purity, 97.4%; lot DECO-97-152-1) at a dose of 500 mg/kg bw by gavage in 0.5%
methylcellulose. Excreta were collected at 24-h intervals for 48 h after dosing, when the animals
were sacrificed. The primary aim was to investigate hydroxylation at the 3- and 6- positions of the
quinoline ring of quinoxyfen. Excreta samples were pooled, treated with sulfatase/glucuronidase,
extracted and analysed using electrospray ionization LC/MS and LC/MS/MS to determine levels of
3-hydroxy and 6-hydroxy-quinoxyfen.
Only limited data were presented in the report owing to the very low levels of hydroxy-metabolites
detected. In the 0–24 h faecal sample, 0.012% of the administered dose was present as
3-hydroxy-quinoxyfen, primarily as a conjugate. Initially, low levels of 3-hydroxy-quinoxyfen were
detected in urine samples, but this was not confirmed in subsequent analyses. Further analytical work
by Pearson & Reeves (2005) indicated that the compound thought to be 3-hydroxy-quinoxyfen was
actually 2-oxo-quinoxyfen. No detectable levels of 6-hydroxy-quinoxyfen were found in the urine or
faeces, representing < 0.0004% and < 0.004% respectively of the administered dose (Brzak, 2001).
Goats
TRR in excreta (urine, faeces), milk and tissues (kidney, liver, fat) from goats (see Dunsire
& Paul, 1995, above) were characterized and/or identified by TLC and HPLC or GC/MS. The
major component identified in liver was a conjugated form of quinoxyfen (approximately 10–15%
TRR). The only components identified in kidney were quinoxyfen (approximately 3% TRR) and
5,7-dichlorohydroxyquinoline (DCHQ; approximately 2% TRR), with no apparent quinoxyfen
conjugates present. In both kidney and liver, major portions of the TRR were characterized as polar
based on TLC and HPLC characteristics. The major component present in fat was quinoxyfen
(approximately 90% TRR), while milk contained quinoxyfen (approximately 40% TRR) and some
very polar material. Small amounts of radioactivity corresponding to 4-fluorophenol, DCHQ, and
QUINOXYFEN X-X JMPR 2006