Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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The study did not identify a NOAEL as the lowest dose (37.5 mg/kg bw per day) produced
effects on male external genitalia of rats (Inawaka, 2005).
Rabbits
Groups of 18 inseminated New Zealand White rabbits received procymidone (purity, 99.6%) at
a dose of 0, 30, 150, 750 or 1000 mg/kg bw per day in corn oil by oral gavage on days 7–19 of gestation.
Clinical observations, food consumption and body weight were monitored and dams were terminated
on day 30 of gestation. Uteri were examined for live fetuses and intrauterine deaths. Fetuses
were weighed and examined for external, visceral (dissection) and skeletal abnormalities (alizarin
staining). Specific examinations of anogenital distance and external genitalia were not performed.
There was no compound-related maternal toxicity; pregnancy outcome was unaffected and no
evidence of teratogenic potential of procymidone was recorded in any of the groups. The degree of
ossification of the fifth and sixth sternebrae was reduced at 1000 mg/kg bw per day. The NOAEL
for maternal toxicity and teratogenicity was 1000 mg/kg bw per day, the highest dose tested. The
NOAEL for developmental toxicity was 750 mg/kg bw per day on the basis of reduced sternebrae
ossification. The study and procedures were inspected by a quality assurance unit and complied with
the essential elements of OECD test guideline 414 of 1981 (Wickramaratne, 1988; Wickramaratne
et al., 1988b)
Groups of 26 pregnant New Zealand White rabbits were given procymidone (purity, 99.2%) at
a dose of 0 or 125 mg/kg bw per day in a vehicle of 0.5% methylcellulose by gavage on days 6 to 28
of gestation. Clinical signs of toxicity, body weight and food consumption were recorded. The dams
were terminated on day 29 of gestation and received an extensive uterine examination. Live fetuses
were weighed, sexed and examined for abnormalities. A detailed examination of the external genitalia
was performed, the anogenital distance and phallus boundary-genital distance were measured
using a micrometer and the diameter and the ventral gap of the preputial lamella were measured using
a microscope.
Signs of maternal toxicity (reduced food consumption, anorexia, abortion) were evident in the
group receiving procymidone. There were no treatment-related effects on fetal parameters, although
the litter size was lower in the procymidone group than controls (7.4 ± 2.7 vs 9.1 ± 2.8) this was
within the normal range for rabbits. Anogenital distance, the phallus boundary-genital distance and
the diameter of the preputial lamina in live fetuses were similar in both groups (Table 24). The ventral
gap of the preputial lamina was unaffected in male fetuses, but was increased in female fetuses
in the treated group. As a result, the ratio of the ventral gap to the diameter of preputial lamella
was also increased. The relative ventral gap of the preputial lamina to body-weight ratio was not
statistically significantly altered, indicating that this effect might be secondary to pup body weight,
although pup weight was only slightly greater in the group receiving procymidone (Table 24). Only
Table 23. Blood plasma kinetic values in pregnant rats given procymidone by gavage
Parameter
Dose (mg/kg bw per day)
37.5 62.5 37.5 62.5
Gestation day 6 6 19 19
C max
(μg/ml) 3.11 3.91 4.01 4.43
T max
(h) 2 2 4 4
AUC (μg.h/ml) 33 46 38 36
From Inawaka (2005)
AUC, area under the curve of concentration–time.
PROCYMIDONE 349–401 JMPR 2007