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

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Groups of five male and five female Wistar-derived Alpk:AP f
SD rats were exposed to profenofos
(purity, 92.1%) at a nominal concentration of 2 mg/l (analytical concentration, 2.2 mg/) by noseonly
inhalation for 4 h. The particle size of the test aerosol ranged from 3.01 to 3.51 μm MMAD,
with geometric standard deviation in the range of 1.59–1.65. This study was conducted in accordance
with GLP regulations. There were no deaths and only transient signs of respiratory irritation (wet fur,
salivation, piloerection, haunched posture) were observed in all rats during and immediately after
exposure. All males and all except three females had gained weight by the end of the 14-day experimental
period and no treatment-related effects were found at necropsy. The LC 50
(4-h) of profenofos
for males and females combined was > 2.2 mg/l air (Rattray, 2004).
In a similar design of study to the above, groups of five male and five female Sprague-Dawley
rats were exposed (nose only) to profenofos (purity, 89.0%) at an analytical concentration of 2.03 mg/l
for 4 h. The particle size of the test material was 2.5 μm (MMAD). This study was conducted in accordance
with GLP regulations. During the 14-day observation period, there were no signs of gross
toxicity, abnormal behaviour, mortality and no treatment-related effects on body weight or on gross
findings at necropsy. The LC 50
(4-h) for male and female rats was > 2.03 mg/l air (Durando, 2005c).
(d)
Dermal irritation
In a study of primary skin irritation, 0.5 ml of undiluted technical profenofos (purity, 90.4%)
was applied under semi-occlusive dressing to the intact skin of New Zealand White rabbits for 4 h.
This study was conducted in accordance with GLP regulations. Erythema was present at each observation
time until day 21; and oedema was present until day 17 after application. The mean score for
erythema formation at 24, 48 and 72 h was 1.94; that for oedema was 1.61. The primary irritation
index was 3.3 (Kuhn, 1990b).
Three New Zealand Albino rabbits received 0.5 ml of undiluted profenofos (purity, 92.1%) applied
to the skin for 4 h. This study was conducted in accordance with GLP regulations. Very slight to
well-defined erythema and very slight oedema were found at the application site in all rabbits 1 h after
the end of treatment, but the effects had disappeared within 3 days. The primary dermal i rritation
index was 1.2 (Merkel, 2004c). Profenofos was not irritating to the rabbit skin.
In a third study, a single application of 0.5 ml of profenofos (purity, 89.0%) was made to the
skin of three New Zealand Albino rabbits for 4 h. This study was conducted in accordance with GLP
regulations. Well-defined erythema and slight oedema were again noted 1 h after the treatment period.
There were no signs of irritation on day 7, but desquamation was observed at all application sites.
The primary dermal irritation index was 3.1 and profenofos was classified as moderately i rritating to
the skin (Durando, 2005d).
(e)
Ocular irritation
In a study of primary eye irritation, 0.1 ml of undiluted profenofos (purity, 90.5%) was instilled
into the conjunctival sac of the eyes of New Zealand White rabbits. A statement of quality assurance
was provided in the study report. However, no statements were made in the report regarding GLP compliance.
At 1 h after instillation, the maximum average irritation score was 4.3 and 4.0 for the unwashed
and washed eyes. The reactions were limited to a slight transient conjunctivitis (Cannelongo, 1982b).
Similar results were obtained in two more recent studies.
Conjunctivitis was observed in all three New Zealand Albino rabbits 1 h after instillation of
0.1 ml of profenofos (purity, 92.1%). In this study, the conjunctivitis had disappeared within 24 h of
PROFENOFOS 403–443 JMPR 2007