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

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In an additional study on possible isomer-specific acute toxicity in Wistar rats, groups of five
male and five female overnight fasted rats were given dimethomorph E-isomer (purity not stated) as
a single dose of 0, 4000 or 5000 mg/kg bw in 0.1% Tween 80 by oral gavage. Rats were observed for
15 days. The study complied with GLP.
In all dosed groups, signs of toxicity started within 1 h after dosing and included (among others)
posture and locomotion disturbances, salivation, blood-crusted snouts and haemorrhagic lacrimation.
Mortalities were observed between study day 2 and day 7; in the group at the lower dose,
four females and no males died; in the group at the higher dose, two females and four males died.
Findings in rats that died were restricted to the GIT and included erosions. In rats sacrificed at study
termination, congested lungs and opaque eyes were found. The LD 50
for the E-isomer was calculated
to be 4715 mg/kg bw in males and 4754 mg/kg bw in females, in both sexes combined, 4472 mg/kg
bw (Heusener & Jacobs, 1987b).
(b)
Dermal application
To investigate the dermal toxicity of the dimethomorph Z-isomer in Wistar rats, groups of
five males and five females were exposed dermally to the Z-isomer (purity, 98.7%) at a dose of 0 or
5000 mg/kg bw for 24 h and then observed for 15 days. The study complied with GLP.
No signs of toxicity and no mortalities were observed. Therefore, the LD 50
was greater than
5000 mg/kg bw in males and females (Heusener & Eberstein, 1985).
Dermal toxicity was investigated in a second study in Fischer 344 rats. Groups of five males
and five females exposed dermally to dimethomorph (purity, 98.5%; E : Z, 46 : 54) at a dose of
2000 mg/kg bw for 24 h and then observed for 14 days. The study complied with GLP.
No signs of toxicity and no mortalities were observed. Therefore, the LD 50
was greater than
2000 mg/kg bw in males and females (Gardner, 1989)
(c)
Exposure by inhalation
Groups of five male and five female Wistar rats were exposed by inhalation to dimethomorph
Z-isomer (purity, 98.7%) at a concentration of 4.24 mg/l (the highest concentration attainable) in a
whole-body chamber for 4 h. 56% of particles had a mean aerodynamic diameter of 5.5 μm or less.
Animals were then observed for 14 consecutive days. The study complied with GLP.
All rats survived till study termination. During the exposure, the rats showed changes in posture
and respiratory patterns. Noticeable breathing was resolved after 5 days. Within the first 2–3
days, reduced feed intake and reduced body-weight gain was found. Therefore, the median lethal
concentration (LC 50
) of the Z-isomer was greater than 4.24 mg/l for males and females (Jackson &
Hardy, 1986).
(d)
Dermal and ocular irritation
The dermal and ocular irritation potential of dimethomorph was investigated in New Zealand
White (NZW) rabbits. The test compound was dimethomorph (purity, 98.5%; E : Z, 46 : 54). For dermal
irritation, three rabbits (two males, one female) were exposed to 500 mg of test compound for 4 h
under semi-occlusive conditions and observed for another 72 h after removal. For ocular irritation,
three animals (one male, two females) were given 50 mg of test compound in a volume of 0.1 ml into
the conjunctival sac of one eye. The eyes were not rinsed. The study complied with GLP.
In the test for dermal irritation, no signs of an irritating potential were recorded.
In the test for ocular irritation, all rabbits showed reddened conjunctivae and slight chemosis.
These signs resolved within 4 h after dosing (Gardner, 1989).
DIMETHOMORPH 273–315 JMPR 2007