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

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and the E : Z isomer ratio was approximately 50 : 50 after dilution with non-radiolabelled dimethomorph.
Non-labelled dimethomorph was 98.8% chemically pure. Another four males and four females
served as a control group and were treated with vehicle only. Blood samples at different time intervals
from 0.25 h to 144 h after dosing were collected and analysed for radioactivity. The study complied
with GLP.
In the groups receiving the lower dose, values for both sexes were comparable; t max
was reached
at < 3h, terminal t 1/2
was 59–68 h and AUC 0–∞
at 10–15 μg × h/g (Table 8). In the groups receiving
the higher dose, increased c max
and AUC 0–∞
values were found in females and this correlated with a
prolonged half-life.
Total radioactive residues (TRR) in plasma and erythrocytes 168 h after treatment were below
the limit of detection (LOD) in both rats of groups at the lower dose and in the plasma of rats in
groups receiving the higher dose (LOD at lower dose, 0.020–0.022 ppm; LOD at higher dose, 0.201–
0.223 ppm). In the groups at the higher dose, TRR in erythrocytes were 0.75 ppm and 0.939 ppm in
male and female rats, respectively (Afzal & Wu, 1995a).
To investigate the tissue distribution of dimethomorph, groups of nine male and nine female
Sprague-Dawley rats (Crl:CD BR) were given [ 14 C]dimethomorph as single oral doses at 10 mg/kg
bw or 500 mg/kg bw by gavage. The test compound was uniformly chlorophenyl-ring labelled [ 14 C]
dimethomorph (radiochemical purity, 96%) and had a specific activity of 0.363 GBq/mmol and the
E : Z isomer ratio was approximately 50 : 50 after dilution with non-radiolabelled dimethomorph
(purity, 98.8%). Another three males and three females served as a control group and were treated
with vehicle only. At t max
, 24 h and 168 h after dosing, three males and three females from each group
were killed and tissues collected for TRR analysis. T max
values were derived from a previous study
(Afzal & Wu, 1995a) considering the lower bounds of t max
ranges in actual dosing groups; for females
at the lower dose, t max
was set at 1.5 h; for males at the lower dose at 0.5 h; and for males and females
at the higher dose at 8 h. The study complied with GLP.
No signs of toxicity were recorded in any group. Highest TRR levels in all dosed groups at t max
and 24 h after dosing were found in the GIT and contents, followed by the carcass and liver (Table
9 and Table 10). In liver, maximal TRR values were 1.05% of the administered dose. In all other
organs, low levels of less than 0.1% were observed even at t max
and they were significantly depleted
within 24 h in the groups at the lower dose. In the groups at the higher dose, a certain delay in depletion
from organs within 24 h was observed when compared with the groups at the lower dose. Levels
at t max
and 24 h were all less than 0.1% of the administered dose. At 168 h, liver contained the highest
levels of residues, with a range of 0.04–0.1% TRR of the administered dose; in all other tissues, TRR
was virtually negligible (Afzal & Wu, 1995b).
To investigate the dermal absorption of dimethomorph, groups of four male Sprague-Dawley
CD rats were exposed dermally to [ 14 C]dimethomorph at a dose of 7.73 or 79.62 mg/kg bw for 8 h.
The test compound was uniformly chlorophenyl-ring labelled [ 14 C]dimethomorph (radiochemical
purity, 96%; purity, 98.8%) and had a specific activity of 0.363 GBq/mmol and the E : Z isomer ratio
was approximately 45 : 55. The chemical purity of dimethomorph before labelling was 97.6%. The
study complied with GLP.
In the group at the lower dose, 4.75% of the applied dose was absorbed, based on the sum of
radioactivity recovered 168 h after topical application in urine, faeces, cage wash, carcass, blood
and untreated skin. In the group at the higher dose, 1.2% of the applied dose was absorbed (Bounds,
1995).
1.2 Effects on enzymes and other biochemical parameters
No information was available.
DIMETHOMORPH 273–315 JMPR 2007