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

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days 14 to 21. Increased relative liver weight was noted at doses of 5000 ppm and greater in males
and females, and in absolute liver weight only in males at 20 000 ppm. The changes in liver weight
were not associated with any histopathological or clinical chemistry change and were not considered
to be adverse.
There was no evidence of toxicity in the studies of prenatal developmental toxicity in rats or
rabbits. The NOAEL in both studies was 1000 mg/kg bw per day on the basis of absence of toxicity
to dams or fetuses at the highest dose tested. Zoxamide was not teratogenic in rats or rabbits.
Zoxamide was not neurotoxic in a study of acute neurotoxicity at doses of up to 2000 mg/kg
bw. No adverse effects were seen during neurological and behavioural examinations performed during
routine repeat-dose studies with zoxamide.
Studies on two plant metabolites of zoxamide—RH-141,452 (3,5-dichloro-4-hydroxymethyl
benzoic acid) RH-141,455 (3,5-dichloro-1,4-benzene-dicarboxylic acid)—formed to a limited extent
in rats, showed them to be rapidly absorbed and rapidly excreted, essentially unchanged; to have low
acute oral toxicities to mice (LD 50
s, > 5000 mg/kg bw), and to give negative results in assays for gene
mutation with strains of Salmonella typhimurium.
There were two reports of mild adverse effects after exposure to a diluted formulation containing
zoxamide and mancozeb. In one case there was a report of skin irritation, in the other “flu-like”
symptoms were reported. The Meeting considered it to be unlikely that these effects were related
directly to exposure to zoxamide.
Toxicological evaluation
An acceptable daily intake (ADI) of 0–0.5 mg/kg bw was established for zoxamide based on
the NOAEL of 48 mg/kg bw per day in the 1-year study in dogs, on the basis of reduced body-weight
gain in females at 255 mg/kg bw per day.
An acute reference dose (ARfD) was considered to be unnecessary for zoxamide as zoxamide
is of low acute toxicity, did not produce developmental effects and did not produce any other
significant effects after acute exposures.
Levels relevant to risk assessment
Species Study Effect NOAEL LOAEL
Mouse
Rat
Two-year studies of toxicity Toxicity 7000 ppm, equal to —
and carcinogenicity a 1021 mg/kg bw per day c
Carcinogenicity
7000 ppm, equal to
1021 mg/kg bw per day c —
Two-year studies of toxicity Toxicity 20 000 ppm, equal to —
and carcinogenicity a 1058 mg/kg bw per day c
Carcinogenicity
20 000 ppm, equal to —
1058 mg/kg bw per day c
Multigeneration study of Reproductive toxicity 30 000 ppm, equal to —
reproductive toxicity a 1474 mg/kg bw per day c
Parental toxicity
30 000 ppm, equal to —
1474 mg/kg bw per day c
Offspring toxicity 30 000 ppm, equal to —
1474 mg/kg bw per day c
Developmental toxicity b Maternal toxicity 1000 mg/kg bw per day c —
Embryo/fetotoxicity 1000 mg/kg bw per day c —
ZOXAMIDE 487–522 JMPR 2007