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

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doses of up to 1.0 mg/kg bw per day caused any adverse effect on reproduction in Fischer 344 rats.
The NOAEL was 0.05 mg/kg bw per day on the basis of hepatocellular hypertrophy at 1.0 mg/kg
bw per day. This effect was not regarded as being relevant to humans. The NOAEL for effects of
relevance to humans was the highest dose tested, 1 mg/kg bw per day (Jeffries et al., 1985).
Table 5: Fertility index of F344 rats fed diets containing racemic haloxyfop acid
Generation Fertility index (%)
Adults mated Pups produced 0 mg/kg bw
per day
0.005 mg/kg bw
per day
0.05 mg/kg bw
per day
1.0 mg/kg bw
per day
F 0
F 1a
83 93 93 97
F 0
F 1b
87 87 97 93
F 1b
F 2a
63 57 67 53
F 1b
F 2b
73 50 47* 47*
F 1b
F 2c
70 43 50 40*
F 2b
F 3a
53 63 53 67
F 2b
F 3b
77 80 83 90
F 2c
Cross-mating 90 90 83 93
From Jeffries et al. (1985)
* Statistically significantly different (p < 0.05) from the value for untreated controls (0 mg/kg bw per day).
(b)
Developmental toxicity
Rats
In a GLP-compliant study of developmental toxicity, groups of 30 mated female Fischer 344
rats were given oral doses of the sodium salt of racemic haloxyfop (purity, 99.7%) at 0, 0.1, 1.0 or
7.5 mg/kg bw per day by gavage on days 6 to 15 of gestation. On day 21 of gestation, all surviving
dams were killed and autopsied. Livers were weighed and liver plus other tissues were fixed, but
histopathology was not performed. Uteri were examined for number of live and dead fetuses, position
of fetuses, number and position of resorption sites, number of corpora lutea, sex, body weight and
length of fetuses, and any overt fetal malformations. Apparent non-pregnancy was confirmed by
staining the uterus with sodium sulfide. At least half the fetuses from each litter were examined by
microdissection for evidence of visceral malformations. The remaining fetuses were examined for
skeletal malformations. No maternal deaths occurred during the study and no clinical signs were
seen. At the highest dose (7.5 mg/kg bw per day), there was decreased feed intake and decreased
body-weight gain on days 6 to 8 of gestation, low body weight when compared with that of controls
on days 16 to 21, and increased intake of water on days 12 to 20. There were no effects on mortality,
clinical signs, or liver weight of the dams. Pregnancy rate was not affected. Litter data showed no
effects on number of resorbed implantations, pre-implantation loss, litter size, sex ratio, fetal weight
or fetal length. There was no effect of treatment on the numbers of any visceral malformations in
fetuses. The only skeletal effect was a significantly increased incidence (p < 0.05) of fetuses with
incompletely ossified centra of thoracic vertebrae in the group at the highest dose (6% fetuses; 33%
litters) when compared with the rate in controls (fetuses, 1%; litters, 8%). The Meeting concluded that
no embryotoxicity or teratogenicity was seen in this study, and that the NOAEL was 1.0 mg/kg bw per
day on the basis of delayed ossification in fetuses at 7.5 mg/kg bw per day (Hayes et al., 1983).
Rabbits
In a GLP-compliant study of developmental toxicity, groups of 30 mated female New Zealand
White rabbits were given the sodium salt of racemic haloxyfop (purity, 99.7%) as an oral dose at 0,
HALOXYFOP X-X JMPR 2006