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

72
1% Tylose CB 30.000. The injection sites were examined after 24 h. One week after the i ntradermal
induction, the second phase of induction was conducted, consisting of two percutaneous a pplications
separated by an interval of 24 h of 2 × 2 cm filter paper squares containing 25% boscalid under
o cclusive dressings. The challenge was performed 2 weeks after the dermal induction, by applying
5% boscalid on filter paper under occlusive dressing for 24 h. Skin reactions were scored at 24 h and
48 h after patch removal. After the intradermal application of 5% boscalid in 1% aqueous Tylose CB
30.000, there was a well defined erythema and moderate edema in all guinea-pigs.
Separate tests using α-hexylcinnamaldehyde as a positive control had been conducted twice
per year in the laboratory concerned to demonstrate the continuing ability of the test procedures to
detect sensitizing compounds.
One guinea-pig in the group receiving boscalid and one guinea-pig in the vehicle control
group died from pneumonia unrelated to treatment. The numbers of guinea-pigs with skin reactions
after the challenge are summarized in Table 22. A few animals (4 out of 19) in the group receiving
boscalid showed skin reactions at challenge, while vehicle alone caused no skin irritation (Wiemann
& Hellwig, 1998a; Wiemann, 2000d).
Table 22. Maximization test in guinea-pigs exposed to boscalid: results
of challenge
Group
No. of positive reactions/No. of guinea-pigs tested
24 h 48 h Total
Control group 0/10 0/10 0/10
Test group 3/19 4/19 4/19
From Wiemann & Hellwig (1998a) and Wiemann (2000d)
The evaluation criteria used were those of the EEC Directive 93/21 for the 18th Amendment
of the Directive 67/548 EEC (Publication No. L 110A, May 4th, 1993). This requires a minimum
of 30% of the test animals to show skin reactions for a classification as a sensitizer. On the basis of
these criteria, the results indicated that boscalid is non-sensitizing, since only 4 out of 19 guinea-pigs
(21%) showed a very slight skin reaction at challenge.
2.2 Short-term studies of toxicity
Mice
Groups of 10 male and 10 female C57BL mice were given diets containing boscalid (batch
No. N 26, purity, 95.3%) at a concentration of 0, 150, 1000, 4000 or 8000 ppm, equal to 0, 29,
197, 788 and 1518 mg/kg bw per day in males and 0, 42, 277, 1184 and 2209 mg/kg bw per day in
females, for about 3 months. The stability of boscalid in the diet was verified and the homogeneity
of the dietary mixtures was verified before the start of the study. Analyses for correct concentrations
were performed before the study start and at week 8.
Food consumption and body weight were determined once per week. The state of health was
checked twice per day. Blood samples were taken from all mice for haematology and blood chemistry
examination at the end of the dosing period. All mice were subjected to complete gross examinations,
and weights of selected organs were determined. Histopathological examinations were conducted on
all organs from the control group and the group at the highest dose and on lung, liver, kidneys and all
gross lesions from all dose groups.
There were no mortalities in the study and boscalid did not cause clinical signs of toxicity in
any of the dose groups. There were no boscalid-related effects on body weight, food consumption
BOSCALID X-X JMPR 2006