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

326
96%) at a concentration designed to give doses of 0.002, 0.02, 0.2 and 2 mg/kg bw per day. A control
group of 15 males and 15 females received basal diet. All mice were killed at the end of the treatment
period and autopsied. Weights of brain, heart, liver, kidneys and testes were recorded. Terminal
samples of blood were taken for haematology and clinical chemistry. A wide range of tissues from
controls and mice at the highest dose were examined microscopically. For the other treatment groups,
only the liver, gall bladder and kidneys were examined microscopically. There were no treatmentrelated
deaths during the study and no abnormal behaviour or signs of toxicity were observed. There
was reduced body weight in the females at 2 mg/kg bw per day when compared with concurrent
controls from the sixth day of treatment onwards, but the body weights of all groups of males were
unaffected. Food consumption was unaffected by treatment. There were no treatment-related effects
on haematological parameters. Clinical chemistry results showed a statistically significant increase
(p < 0.05) in serum alkaline phosphatase (AP) activity in the group of males at the highest dose
(2 mg/kg bw per day) (22% greater than control values) and a small non-significant increase in this
parameter in females (8% greater than control values). Absolute and relative weights of liver were
also increased in male and female mice in the group at the highest dose and the livers appeared
slightly enlarged and dark at autopsy. Microscopically, the centrilobular hepatocytes appeared
enlarged in all males and 8 out of 10 females in the group at the highest dose and the cytoplasm
of these cells was more eosinophilic and appeared more homogeneous than in controls. It is likely
that the hepatocellular hyperplasia seen in this study was caused by a mode of action involving
hepatocellular peroxisome proliferation that is not relevant to humans. The NOAEL was 0.2 mg/kg
bw per day, on the basis of increased serum AP activity at 2 mg/kg bw per day (Gorzinski et al.,
1982a).
In a 36-week feeding study that was performed in accordance with GLP, groups of 12 male
and 12 female B6C3F 1
mice were fed diets containing racemic haloxyfop acid (purity, 96%) at a
concentration designed to give dosaes of 0 (control group) or 2 mg/kg bw per day. An additional
group of 10 males and 10 females was given a dose of 0.02 mg/kg bw per day. All mice were
killed at the end of the treatment period and autopsied. Weights of brain, heart, liver, kidneys and
testes were recorded. Terminal samples of blood were taken for haematology and clinical chemistry.
Only the liver, gall bladder and kidneys were examined microscopically. Two males and one female
from the group at the highest dose and one female from the group at the lowest dose died during
the treatment period. No abnormal behaviour or signs of toxicity were observed and body weights
and food consumption were unaffected by treatment. Haematology showed significantly decreased
erythrocyte count in females at the highest dose but increased erythrocyte count and decreased
erythrocyte volume fraction in the group at the lowest dose. These changes were not thought to be
treatment-related. Clinical chemistry results showed increases in serum AP activity in males at the
highest dose (105% greater than control values and statistically significant) and in females (8%
greater than control values and non-significant). Absolute and relative weights of liver and kidney
were increased in male and female mice in the group at the highest dose and the livers appeared
slightly enlarged and dark at autopsy. Microscopically, the centrilobular hepatocytes appeared
enlarged in all males and in 8 out of 10 females in the group at the highest dose. Also, the cytoplasm
of these cells was more eosinophilic and appeared more homogeneous than in controls. One male
mouse at the highest dose had a small focus of basophilic hepatocytes which the authors of the study
suggested was consistent with the hepatocellular adenoma or type A nodule that is frequently seen
in B6C3F 1
mice. It is likely that the hepatocellular hyperplasia seen in this study was caused by a
mode of action involving hepatocellular peroxisome proliferation that is not relevant to humans.
The kidneys of the males at the highest dose had decreased cytoplasmic vacuolation of the proximal
convoluted tubule cells. The NOAEL was 0.02 mg/kg bw per day on the basis of increased serum AP
activity and effects on the renal proximal convoluted tubules seen at 2 mg/kg bw per day (Gorzinski
et al., 1982a).
HALOXYFOP X-X JMPR 2006