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

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In a GLP-compliant study, groups of 15 male and 15 female Fischer 344 rats were fed diets
containing racemic haloxyfop acid (purity, 96%), receiving doses of 0 (control), 0.002, 0.02, 0.2
or 2.0 mg/kg bw per day for 16 weeks. Blood samples were taken from 10 males and 10 females
per group after 84, 99 and 106/7 days on test and haematology (total leukocyte count, differential
leukocyte count, erythrocyte count, erythrocyte volume fraction and haemoglobin) was performed.
Urine analysis (specific gravity, pH, glucose, protein, ketones, occult blood, bilirubin and urobilinogen)
was performed at the end of the treatment period. All rats were killed for autopsy at the end of
the treatment period and the following organs were weighed: brain, liver, kidneys, heart, thymus
and testes. Clinical chemistry (glucose, AP, ALT, BUN, total protein, albumin and globulin) was
performed on serum from blood taken at autopsy. Histopathology was performed on a wide range of
tissues from 10 males and 10 females of the control group and group at the highest dose. For the other
treatment groups, only the liver was examined microscopically.
The treatment had no effect on mortality, behaviour, clinical signs and body weight or food
consumption. However, the growth of several of the rats in all groups was adversely affected by a
viral infection. There were no treatment-related effects on haematological parameters. Serum AP
activity was significantly (p < 0.05) increased by 24% in males given 2.0 mg/kg bw per day. Urine
analysis showed no treatment-related effects. Absolute and relative liver weights were significantly
(p < 0.05) increased in the group of females at the highest dose. In males, there were dose-related
increases in absolute and relative liver weights, with the absolute weight being significant (p < 0.05)
for the groups given 0.2 or 2.0 mg/kg bw per day and the increase in relative liver weight being
significant (p < 0.05) at all doses tested. Small but significant (p < 0.05) increases in the relative
weights of heart and kidneys were seen in females at 0.02 or 2.0 mg/kg bw per day. At autopsy, all
males at the highest dose and two of the males at 0.2 mg/kg bw per day had visibly enlarged livers
and several of the rats of either sex at 0.2 or 2.0 mg/kg bw per day had discoloured kidneys (darkened
or greenish appearance). Microscopic examination showed hepatocellular hypertrophy in males at
0.2 or 2.0 mg/kg bw per day, with the effect being more severe at the highest dose. The hepatocytes
of males and females at the highest dose had an increased degree of cytoplasmic homogeneity. No
renal histopathology was seen.
The NOAEL was 0.02 mg/kg bw per day on the basis of hepatocellular hypertrophy (not
relevant to humans) seen at 0.2 mg/kg bw per day or more. The small but statistically significant
increases in the weights of liver, heart and kidneys that were seen at 0.02 mg/kg bw per day or less
were not considered to be toxicologically significant as they were not associated with any effects on
clinical chemistry or histopathology. The NOAEL for effects of relevance to humans was 0.2 mg/kg
bw per day on the basis of the slightly increased serum AP activity at 2 mg/kg bw per day (Gorzinski
et al., 1982c).
In a GLP-compliant study, groups of 12 male and 12 female Fischer 344 rats were fed diets
providing racemic haloxyfop acid (purity, 96%) at a dose of 0 (control), 0.02 or 2.0 mg/kg bw per day
for 37 weeks. Blood samples were taken from eight males and eight females per group after 258 days
and haematology was performed (total leukocyte count, differential leukocyte count, erythrocyte
count, erythrocyte volume fraction and haemoglobin). Urine analysis (specific gravity, pH, glucose,
protein, ketones, occult blood, bilirubin and urobilinogen) was performed at the end of the treatment
period. All rats were killed for autopsy at the end of the treatment period and the following organs
were weighed: brain, liver, kidneys, heart, thymus and testes. Clinical chemistry (glucose, AP, ALT,
BUN, total protein, albumin and globulin) was performed on serum from blood taken at autopsy. The
liver and kidneys of all rats were examined microscopically. In addition, sections of kidney from five
males in the control group and the group at the highest dose were treated with special stains (Zeihl
Nielson acid fast, PAS, Gomori iron, Von Kossa calcium, Hall bilirubin and Dahl calcium) and were
examined by microscope.
HALOXYFOP X-X JMPR 2006