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

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Ophthalmoscopic examinations performed every 2 weeks did not reveal any alterations in the
lens in any dog.
There were no clear differences between the dogs in any of the haematological parameters
measured. Although the male in the reference group had lower erythrocyte, haemoglobin and erythrocyte
volume fraction values at termination than did the males in the recovery group (as seen in the
6-month feeding study in dogs; O’Connor et al., 1987), lower values were also evident before the
exposure period began. The values for leukocytes in the male in the reference group and erythrocytes
in the female in the reference group were clearly above the 95% upper limit of the range for historical
controls, but these variations were not considered to be related to treatment.
There were also no clear differences in clinical chemistry parameters between dogs in the
reference and recovery groups. There was an apparent increase in alkaline phosphatase activity in
the male and female in the reference groups, which is consistent with findings in the 6-month and
12-month feeding studies in dogs (O’Connor et al., 1987; Rudzki et al., 1988); the value for the male
at 19 weeks was also clearly above the 95% upper limit of the range for historical controls, while the
value for the female was within the range.
Analysis of organ weights revealed increased absolute and relative liver weights in the male but
not in the female in the reference group. The few other differences observed were considered not to
be related to treatment.
Macroscopic examinations did not reveal any treatment-related findings. The few findings noted
(congestion in the spleen, worms in the small intestine, foci in the lungs, discoloration in the cervical
lymph node, cysts in the ovaries and thickening in the vagina) were considered to be spontaneous
findings usually encountered in dogs of this strain and age.
There were no treatment-related histopathology findings and there were no histological alterations
of any sort in the eye. All findings that were seen in dogs in the reference groups were also seen
in those in the recovery groups, and were not unusual in young beagle dogs (Janiak et al., 1989). The
Meeting concluded that treatment of single male and female dogs with difenoconazole in this small
study did not result in the formation of cataracts.
3. Observations in humans
3.1 Medical surveillance on personnel at manufacturing sites
Manufacturing employees are medically examined by company physicians at the beginning
of their employment and then routinely once per year. In Switzerland, routine medical examinations
according to the criteria of the Swiss Accident Insurance Institution (SUVA) include: anamnesis;
physical examination including blood pressure measurement; blood analysis: haemoglobin, erythrocytes,
leukocytes, thrombocytes, complete blood count, blood sedimentation rate, blood sugar, blood
pressure, cholesterol, triglycerides, ALT, aspartate aminotrasferase, alkaline phosphatase, bilirubin,
creatinine and urate; and urine analysis.
Difenoconazole has been manufactured in production plants at Monthey in Switzerland and
formulated at various sites around the world. Data was sought from all sites handling either the technical
active ingredient or formulated product. A request for data on adverse health events covering
the years 1992 to 2002, carried out in December 2002, provided the information that questionnaires
were sent to those responsible for the production sites and company physicians:
Monthey, Switzerland (production); reporting period, 1992 until December 2002
Difenoconazole had been handled since 1992 in three buildings, with an estimated 5300 tonnes
being produced over the decade. In 2002, about two thirds of the product was handled and packed as
DIFENOCONAZOLE 201–272 JMPR 2007