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

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months of treatment. At the same time-points, clinical chemistry and urine analysis was performed
on the 10 males and 10 females per group not designated for haematology. In addition, bone-marrow
smears taken at 3 months were examined. During the last week of treatment, ophthalomoscopy was
performed on all rats in the control group and those at the highest dose. At termination, the rats were
killed and necropsied. Selected organs were weighed. An extensive range of tissues from rats in the
control group and those at the highest dose, and the testes, epididymes, prostate, seminal vesicles,
liver, kidneys, heart, spleen and abnormal tissues of all rats were histologically examined. Livers
from six males and six females per group were examined by electron microscopy. Hepatic aminopyrine-N-demethylase
activity was measured in liver samples from 10 males and 10 females per group.
Statements of adherence to QA and GLP were included.
No effects of treatment on mortality, clinical signs, ophthalmoscopy and relative organ
weights were observed. Minor effects on haematological parameters were considered not to be toxicologically
relevant. The body-weight gain of males at the highest dose was consistently reduced
(±10%) throughout the study. Food consumption was reduced in males at 50 and 250 ppm by 12%
and 13%, respectively. At 13 weeks, plasma triglyceride concentrations were reduced (42% and
59%, respectively). Urinary glucose concentration was increased (49% and 69%) in males at 50
and 250 ppm, respectively. However, since the increases were small and similar increases in urine
glucose concentrations were observed before treatment (54% and 79% at 50 and 250 ppm, respectively)
this effect was not considered to be treatment-related. The results of gross examinations were
not reported. No treatment-related changes were revealed by optical microscopy of organs. Electron
microscopy of the liver showed mild proliferation of smooth endoplasmic reticulum in the hepatocytes
of three males in the groups at 50 ppm and 250 ppm. Hepatic aminopyrine-N-demethylase
activity was increased in males at 50 or 250 ppm by 34% and 68%, respectively, and in females at
250 ppm by 46%.
On the basis of reduced body-weight gain and food consumption in males at 250 ppm, the
NOAEL was 50 ppm, equal to 2.6 mg/kg bw per day (Lindsay et al., 1981). The Meeting noted that
the 1984 JMPR had stated that a NOEL could not be established owing to haematological effects in
all treatment groups. However, the effects were very small (generally < 3%, and 6% for mean cell
volume at 250 ppm).
In a 3-month feeding study, groups of 20 male and 20 female Alderley Park (Alpk/AP) rats
were fed diets containing lambda-cyhalothrin (P321; purity, 96.5%) at a concentration of 0, 10, 50,
or 250 ppm (equivalent to 0, 0.5, 2.5 and 12.5 mg/kg bw per day). The rats were checked daily for
clinical signs. Detailed clinical examinations and body weights were assessed at the start of treatment
and weekly thereafter. Food consumption was measured weekly. Haematology was performed
on 10 males and 10 females per group at the start, and at 1 and 3 months of treatment. At the same
time-points, clinical chemistry and urine analysis was performed on the 10 males and 10 females
per group not designated for haematology. During the last week of treatment, ophthalomoscopy
was performed on all rats in the control group and at the highest dose. After 13 weeks, the rats
were killed and necropsied. Selected organs were weighed. A selection of tissues from rats in the
control group and at the highest dose, and the liver, kidneys, lungs and abnormal tissues of all rats
were examined histologically. Hepatic aminopyrine-N-demethylase activity was measured in liver
samples of six males and six females per group. Statements of adherence to QA and GLP were
included.
No toxicologically relevant effects on clinical signs, ophthalmoscopy, haematology, clinical
chemistry and urine analysis were observed. Body-weight gain and food consumption were reduced
in the group at the highest dose (males, 11%; females, 7–9%). Blood triglyceride concentrations,
measured after 1 and 3 months of treatment, were reduced by 28–32% in males at the highest dose
and by 15–17% in males at the intermediate dose. A slight increase in relative liver weight (8%) was
LAMBDA-CYHALOTHRIN 173–200 JMPR 2007