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

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of the study were unremarkable. On the basis of these data, difenoconazole was considered to be essentially
non-toxic when applied topically under occlusion to intact rabbit skin (Mastrocco et al., 1987a).
(c)
Inhalation
A test for the acute toxicity of difenoconazole technical (batch No. P 012060, purity, 96.2%)
was conducted in a group of Tif RAI f (SPF) rats (five of each sex) exposed by inhalation. Exposure
was in a head/nose inhalation system for 4 h to a mean analysed atmospheric concentration of
3967/3285 (nominal/gravimetric) mg/m 3 air (technically highest achievable concentration). In order
to maintain a constant aerosol concentration with acceptable particle size distribution, it was necessary
to blend difenoconazole with 5% Sipernat 50S, an inert silica. The aerosol was generated from
the solid test material by means of a brush-feed micronizing jet mill. The aerosol from the dust generator
was diluted with filtered humidified air. Owing to the properties of the test material, it was not
possible to generate higher concentrations of aerosol. A control group of equal size was exposed to
purified air under the same conditions as the test group. The rats were examined for clinical signs of
toxicity and mortality during and after exposure and daily thereafter. Individual body weights were
recorded immediately before exposure, on day 7 and day 14. The study was terminated 14 days after
dosing. Autopsy was performed on all rats. Particular attention was given to the respiratory tract.
No rats died during the study. Symptoms observed in rats of both sexes and to a similar extent
were dyspnoea during and after exposure and piloerection, hunched posture and reduced locomotion
after exposure. Reduced locomotion was not observed after the day of exposure, while hunched
posture was also observed on the day after exposure, dyspnoea persisted to include day 4 and piloerection
persisted to include day 6. All symptoms disappeared within 7 days. In comparison with rats
in the control group, the males showed a lower body-weight gain in the first week and the females
showed a higher body-weight gain in the second week after exposure. No treatment-related macroscopic
findings were observed. The median lethal concentration (LC 50
) for difenoconazole suspended
in air was > 3300 mg/m 3 (3.3 mg/l) for male and female rats (Hartmann, 1991).
(d)
Dermal irritation
Difenoconazole technical (purity, 91.5%) was evaluated for acute dermal irritation potential in
three male and three female Hra:(NZW)SPF rabbits. Difenoconazole (0.5 g) was moistened with 0.9%
saline and applied to a 6.25 cm 2 gauze pad that was placed on the shaved dorsal area. The gauze patch
was covered with plastic, secured with tape and left for 4 h. Thereafter, patches were removed and the
test sites were washed using tap water and paper towels. Adjacent areas of untreated skin of each rabbit
served as controls for the test. Signs of skin erythema or oedema were scored after 30 min, 24 h, 48 h,
and 72 h after dosing. Dermal irritation was scored and recorded according to the Draize technique
One female was found with grade 1 erythema after 30 min. After 24 h, this reaction had cleared.
No other skin reactions were noted with any rabbit (Glaza, 1991a). The Meeting concluded that
difenocoazole was very slightly and transiently irritating to the skin of rabbits.
(e)
Ocular irritation
Difenoconazole technical (purity, 91.5%) was evaluated for acute eye irritation potential in
New Zealand White (Hra:(NZW)SPF) rabbits (initial body weight, 2442–2696 g). Three males and
three females in group 1 and two males and one female in group 2 were used. Each rabbit received 0.1
ml of difenoconazole placed into the everted lower lid of the right eye. The upper and lower lids were
gently held together for 1 s to prevent loss of material and then released. In group 1 (three males and
three females), the eyes of the rabbits were not washed, while in group 2 (two males and one female),
the eyes of the rabbits were washed with lukewarm tap water for 60 s starting 30 s after instillation
of difenoconazole. The eyes were examined at 1, 24, 48 72 and 96 h after dosing. Eye irritation was
scored and recorded according to the Draize technique.
DIFENOCONAZOLE 201–272 JMPR 2007