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females at the highest dose, total protein and creatinine concentrations were decreased and urea
nitrogen, potassium and phosphorus concentrations were increased. Urea nitrogen was also increased
in females at the intermediate dose. In both sexes receiving the highest dose, urine volumes were
significantly increased and protein concentrations were decreased in males—three out of five males
did not excrete any protein in the urine. Similarly to rats found dead/killed in a moribund condition
before termination that showed thickened and congested large and small intestines, rats at the highest
dose at termination showed thickened stomachs and males also showed thickened ileums. Males at
the highest dose had empty seminal vesicles. Absolute pituitary weights of males at the intermediate
(9 ± 2.2 mg) and highest dose (9 ± 1.0 mg), and of females at the highest dose (7 ± 0.6 mg) were
reduced relative to controls (controls: males, 14 ± 3.6 mg; females, 14 ± 2.1), as was the absolute
uterus weight of females at the highest dose. In the group at the highest dose, absolute weights of
adrenals were increased in males and relative liver weights were increased in females. No histopathology
was performed on organs.
On the basis of decreases in absolute pituitary weight in males at 1000 ppm, the NOAEL was
200 ppm, equal to 15.8 mg/kg bw per day (Warren, 1985).
In a second 4-week dose range-finding feeding study, groups of 10 male and 10 female
Sprague-Dawley rats were fed diets containing dimethomorph at a concentration of 0, 2000, 3000, or
4000 ppm, equal to approximately 0, 200, 290, and 370 mg/kg bw per day in males and 0, 220, 300,
420 mg/kg bw per day in females (purity, 96.6%). The rats were examined twice per day for general
health, moribundity and mortality, and weekly detailed clinical examinations were performed. Feed
and water consumption and body-weight development were recorded regularly. At the end of the
study, organ weights were recorded and gross pathology performed. Additionally, histopathology on
livers was performed. The study complied with GLP.
All rats survived until scheduled death. At the highest dose, males and females showed piloerection
and swollen abdomens and perigenital staining were observed in females. In all dosed
females and in males at the highest dose, statistically significant decreases in body-weight gains were
recorded (Table 14). Feed consumption was reduced by 16% in males and 26% in females at the
highest dose. Two males at the highest dose and two females at the intermediate dose and six females
at the highest dose showed distended intestines, in some instances with thickened mucosa and often
filled with fluids or gelatinous material. Body-weight adjusted organ weights were only significantly
changed for livers of rats at 2000 ppm (males, 4%; females, 14%), at 3000 ppm (males, 10%; females,
25%) and at 4000 ppm (males, 13%; females, 36%). Increased dose-related incidences of liver hypertrophy
were found in males at the intermediate and highest dose and in females at the lowest and
intermediate dose and only in one female at the highest dose. In this group of females, at the highest
dosehypertrophy may have been masked by vacuolation in the other females of this group.
On the basis of the body-weight and liver findings, the NOAEL was less than 2000 ppm, equal
to approximately 200 mg/kg bw per day (Scott, 1986).
Table 13. Body-weight gain and feed consumption in rats fed diets containing dimethomorph for
4 weeks
Dietary concentration (ppm) Dose (mg/kg bw) Body-weight gain (g),
weeks 0–4
Feed consumption
(% of control)
Males Females Males Females Males Females
0 0 0 176 51 — —
200 15.8 17.5 157 60 99 100
1000 80.9 81.1 157 57 101 93
5000 305 283.2 23 0.3 62 53
From Warren (1985)
DIMETHOMORPH 273–315 JMPR 2007