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

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of them with signs of improper dosing; three rabbits aborted and two of them had findings in the liver
and/or spleen. Mortalities in all groups were not considered to be treatment-related, while the abortions
at 650 mg/kg bw per day probably were treatment-related (Table 38). There were no additional
clinical or necropsy findings considered to be treatment-related. The decreased body-weight gain
during days 6–12 of gestation coincided with a statistically significant reduced feed intake in this
period (Table 39). Postimplantation losses in females with live fetuses at necropsy were comparable
in all groups. There were no malformations or increased incidences in variations that are considered
to be treatment-related.
The NOAEL for maternal and developmental toxicity was 300 mg/kg bw per day on the basis
of intermittently reduced body-weight gain in dams and abortions at 650 mg/kg bw per day. No
treatment-related malformations were observed (Müller, 1989a).
2.6 Special studies: pharmacology
Thirteen studies on the pharmacological effects of dimethomorph in different species were
performed. They all complied with GLP.
(a)
Anticonvulsive activity in mice
In six male mice, dimethomorph at a dose of 100 mg/kg bw did not suppress leptazol- (pentylenetetrazole)
induced convulsions and therefore the study authors concluded that dimethomorph has
no central nervous system depressing activity (Ainsworth & Wright, 1991a).
Table 38. Postimplantation losses in a study of developmental toxicity in rabbits given
dimethomorph by gavage
Parameter
Dose (mg/kg bw per day)
0 135 300 650
Inseminated females 22 22 22 22
Pregnant females 20 17 18 20
Females found dead 1 0 2 4
Abortions 1 1 0 3
Females with total intrauterine deaths 1 2 0 1
Females with live fetuses at necropsy 17 14 16 12
From Müller (1989a)
Table 39. Body weight gain in dams in a study of developmental toxicity in rabbits given
dimethomorph by gavage
Days of gestation
Body-weight gain (kg)
Dose (mg/kg bw per day)
0 135 300 650
0–6 0.3 0.2 0.3 0.2
6–12 0.1 0.1 0.1 0
12–18 0.1 0.1 0.1 0.1
18–24 0.1 0.1 0.2 0.2
0–28 0.8 0.6 0.7 0.5
From Müller (1989a)
DIMETHOMORPH 273–315 JMPR 2007