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

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the end of dosing. Blood samples were taken from all rats for haematology and blood chemistry
examination at the end of the dosing period. Urine was analysed at the end of the exposure period. All
rats were subjected to complete gross examinations, and weights of selected organs were determined.
Histopathological examinations were conducted on all organs from animals in the control group and
in the group at the highest dose and on lung, thyroid, liver, kidneys and all gross lesions from all
dosed groups.
There were no mortalities in the study and boscalid did not cause clinical signs of toxicity in
any of the dosed groups. There were no boscalid-related effects on body weight or food consumption
at any dose.
Erythrocyte counts and erythrocyte volume fraction values were increased in male rats at a
dietary concentration of 2000 ppm and greater, and haemoglobin concentrations were increased in
male rats at 5000 and 15 000 ppm. No corresponding haematological changes were observed in
female rats, but prothrombin time was significantly reduced in females at 15 000 ppm.
Blood chemistry examination showed dose-dependent, statistically significant increases in
gamma-glutamyltransferase activity in male rats at 2000, 5000 and 15 000 ppm and in female rats
at 5000 ppm and greater. In addition, alkaline phosphatase activity was decreased in female rats
at 500 ppm and greater, having significantly increased at 100 ppm. A decrease in the activity of
this enzyme is generally not considered as adverse. No other enzyme activities were affected by
treatment. Concentration of bilirubin decreased with increasing dose in male rats at 2000 ppm group
and greater, but not in females, and the concentrations of triglycerides were reduced in males and
females at 15 000 ppm. Other blood chemistry changes were increases (in contrast with mice in the
previous study) in total protein and albumin in males at 5000 and 15 000 ppm and in total protein,
albumin, globulin and cholesterol in females at 15 000 ppm.
There were no test-substance related effects seen in urine analysis and ophthalmoscopy.
Organ-weight measurement revealed increased weight of the liver and the thyroids in male and
female rats. Liver weights were significantly increased in the group at 15 000 ppm by approximately
19% in male rats and 23% in female rats. Female rat liver weight was also increased in the group
at 5000 ppm by approximately 9%. Thyroid weights were significantly increased in groups of male
rats at 2000 and 15 000 ppm (but not at 5000 ppm) by approximately 21% and 34% and in groups
of female rats at 5000 and 15 000 ppm by approximately 17% and 31%. Liver weights relative to
body weights were also increased in male and female rats in groups at 5000 and 15 000 ppm and
relative thyroid weights were increased in males at 2000 and 15 000 ppm and in females at 5000 and
15 000 ppm.
Centrilobular (zone 3) hypertrophy was recorded in 8 out of 10 male and 2 out of 10 female rats
at 5000 ppm and in 10 out of 10 male and 7 out of 10 female rats at 15 000 ppm. It was also noted that
in those cases where centrilobular hypertrophy occurred in male rats, fat accumulation was observed
more commonly in the periphery of the lobules than in mid-zonal (zone 2) areas. All other hepatic
lesions were unrelated to treatment.
In thyroids, follicular cell hypertrophy and diffuse hyperplasia of grade 1 (minimal) or 2 (slight)
were recorded in some male rats of all groups. The incidences of grades 1 and 2 hypertrophy and
hyperplasia were 1 out of 10, 2 out of 10, 3 out of 10, 7 out of 10, 7 out of 10 and 8 out of 10 in the
groups at 0, 100, 500, 2000, 5000 and 15 000 ppm, respectively. There were no similar records of
hypertrophy or hyperplasia in female rats, in spite of the organ-weight changes that had been observed.
All other thyroid lesions were unrelated to treatment. Also, no lesions recorded in other organs were
treatment-related. Many of the dose-related hepatic changes that were found are indicative of an
adaptive response to a chemical that is an inducer of enzymes. This hypothesis was examined in
another study that demonstrated a proliferation of smooth endoplasmic reticulum (see below). Such
changes are fully reversible as long as degenerative or necrotic changes do not also occur in the liver.
Degenerative changes were not described in this study. In the thyroid, hypertrophy and hyperplasia
BOSCALID X-X JMPR 2006