toxicological profile for malathion - Agency for Toxic Substances and ...

MALATHION 64
3.2.2.2 Systemic Effects
3. HEALTH EFFECTS
The highest NOAEL values and all reliable LOAEL values for systemic effects in each species and
duration category are recorded in Table 3-2 and plotted in Figure 3-2.
Respiratory Effects. Several reports of malathion poisoning document respiratory difficulties typical
of parasympathetic autonomic stimulation shortly after poisoning (Amos and Hall 1965; Choi et al. 1998;
Crowley and Johns 1966; Dive et al. 1994; Jušić and Milić 1978; Monje Argiles et al. 1990; Namba et al.
1970; Tuthill 1958; Zivot et al. 1993). Doses could be estimated from information in some studies, and
ranged from 214 to 1,071 mg/kg. Even at the lower dose estimates, respiratory distress and bronchorrhea
were common, and most patients required ventilatory support, some for more than 30 days (Monje
Argiles et al. 1990). Pulmonary fibrosis that developed in the second week following the poisoning
episode was also observed in two reports (Dive et al. 1994; Monje Argiles et al. 1990).
Adverse respiratory effects have been described in animals after acute oral exposure to malathion. Severe
respiratory distress was observed in Wistar rats administered approximately 411 mg/kg/day malathion of
unspecified purity in a 7-day dietary study (Ojha et al. 1992). Hemorrhage and hyperemia in the lungs
was reported in male Wistar rats 2 days following administration of a single gavage dose of 1,950 mg/kg
of technical malathion (95% pure), the only dose level tested (Piramanayagam et al. 1996). Without
providing details, the authors (Piramanayagam et al. 1996) stated that by day 12, almost all organs
examined appeared normal. Rats treated for 1–2 weeks with 130 mg malathion/kg/day (purity
unspecified) by gavage developed interstitial pneumonia and emphysema (Piramanayagam and Manohar
2002). Also, pregnant Sprague-Dawley rats administered 500 mg/kg/day technical malathion (purity
unspecified) by gavage 3 times during gestation exhibited dyspnea 2 hours after each dosing (Prabhakaran
et al. 1993). Dyspnea and respiratory distress may be due to stimulation of parasympathetic
postganglionic nerves (muscarinic effects) or to diaphragmatic failure (nicotinic effects).
No respiratory effects (clinical signs or histopathology) were reported in Osborne-Mendel rats
administered up to 622 mg/kg/day technical malathion (95% pure) in the diet for 80 weeks (NCI 1978) or
in Fischer-344 rats administered up to 332 mg/kg/day technical malathion (95% pure) also in the diet for
103 weeks (NCI 1979a). In studies in mice, NCI (1978) reported that male and female B6C3F1 mice
given approximately 2,980 mg/kg/day malathion (95% pure) in the diet began coughing and sneezing
after 72 weeks of treatment; this condition persisted until the end of the study (80 weeks). No such