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

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(b)
Developmental toxicity
Rats
Groups of 25 female Sprague Dawley rats (Crl:CD(SD)BR) were given zeta-cypermethrin
(purity, 89.6%) at a dose of 0, 5, 12.5, 25 or 35 mg/kg bw per day in corn oil by gavage from day 6
to day 15 post coitum. Clinical observations and measurement of body weight and food consumption
were performed daily. Pathological investigations were conducted at the end of the study period
(day 20 of presumed gestation). The ovaries and uteri of each animal were removed and examined for
the number of corpora lutea, and the number and position of implantations, including the numbers
of live fetuses, early and late resorptions, and dead fetuses. The sex and weight of each fetus was
determined, and all fetuses were examined for external malformations. Approximately half the fetuses
were examined for skeletal malformations and the remainder for visceral abnormalities. No animals
died before sacrifice. Clinical observations related to toxicity were limited to the groups at 25 and
35 mg/kg bw per day and primarily comprised ataxia, hypersensitivity, urine-stained abdominal fur,
emaciated appearance and soft faeces. Tremors and convulsions were seen only in one animal at
35 mg/kg bw per day. Maternal necropsy findings were minimal and not dose-related, with a single
animal at 35 mg/kg bw per day having white cloudy fluid in the thorax and pericardium adhering to
the diaphragm, and two animals in the group at 5 mg/kg bw per day having a mammary mass or a
lesion on the back and base of the tail. Relative to the control group, maternal body-weight gains were
significantly reduced by 23% and 51% at 25 and 35 mg/kg bw per day, respectively, during the dosing
period, with an associated reduction in food consumption of 10% and 24%, respectively. Treatment
did not affect the average number of resorptions or fetuses, nor did it affect the number of dams
with viable fetuses. No treatment-dependent differences in average fetal body weights, sex ratios,
percentage dead or resorbed conceptuses were observed. The numbers of fetuses with alterations
(gross external, visceral and skeletal combined) were increased slightly at higher doses (7 out of 390,
9 out of 377, 8 out of 321, 11 out of 384, and 12 out of 347 in increasing order of dose, not statistically
significant), but were not considered to be an effect of treatment, as all abnormalities considered
individually were reported as common in this strain of rat, occurred at fetal or litter incidences that
were not dose-dependent and/or statistically significantly increased relative to controls, and were
within the ranges for their respective historical controls.
The NOAEL for maternal toxicity was 12.5 mg/kg bw per day on the basis of clinical signs of
toxicity and reduced weight gain at 25 mg/kg bw per day and higher. As there was no evidence of
treatment-related effects on fetal developmental or survival in this study, the NOAEL for developmental
toxicity was 35 mg/kg bw per day, the highest dose tested (Hoberman, 1990).
5.5 Special studies
(a)
Neurotoxicity
In a study of acute neurotoxicity, groups of 10 male and 10 female Long Evans rats (Charles
River Laboratories) were given zeta-cypermethrin (FMC 56701; purity, 84.4%) undiluted as a single
dose at 0 (tap water only), 10, 50 or 250 mg/kg bw by gavage on day 0. The animals were observed
twice per day for mortality, a detailed physical exam was performed daily, and body weight was
measured weekly. FOB and testing for motor activity were conducted for two of each sex per group
before treatment and on days 0, 7 and 14. After testing on day 14, five of each sex in the control group
and in the group at 250 mg/kg bw were anaesthetized, perfused in situ with fixative, and given a gross
necropsy. Tissue samples from the nervous system (brain, spinal cord, sciatic, tibial and sural nerves,
Gasserian ganglion, cervical and lumbar dorsal root fibres and ganglia, cervical and lumbar ventral
root fibres), and gastrocnemius muscle were taken for histopathological examination. One female
at 250 mg/kg bw died on day 0 after displaying treatment-related clinical signs. At 250 mg/ kg bw,
CYPERMETHRINS X-X JMPR 2006