Oral exposure

To avoid this confusion it is necessary to separate acute Al intoxication into acute Al gastroenteropathy and acute Al encephalopathy . Chronic Al gastroenteropathy as such probably does not exist, because patients will terminate the oral exposure because of complaints. 

Gastroenterological symptoms due to Al toxicity have been described as massive gastrointestinal intoxication and as peritoneal dialysis fluid contamination with Al [81-83]. 

Compound 11 n o SYVAL ID50 (mpk l 24 h) GR73632-induced foot tapping ID50 (mpk d 24 h) 

NK1 agonist-mediated gerbil foot tapping model (ID50 = 0.33 mpk) [34]. Aprepitant (36), which contains seven fluorine atoms, was subsequently approved by the Food and Drug Administration (FDA) for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. 

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Chronic Toxicity. The effects of repeated oral exposure to phthalates for periods ranging from a few days to 2 years have been studied in a number of animal species including rats, mice, hamsters, guinea pigs, ferrets, and dogs (37). 

Health Hazards. AHyl chloride is a toxic, highly flammable compound that is severely irritating to the skin and mucous membranes. AHyl chloride is considered to be moderately to highly toxic (LD q = 275-700 mg/kg body weight) via oral exposure. Amounts incidental to industrial handling are unlikely to cause injury. Large amounts, however, can cause injury, even death (24,50). 

Hematological Effects. No information was found regarding hematological effects in humans following exposure to methyl parathion. Repeated oral exposure to methyl parathion resulted in decreased mean corpuseular volume in one study and decreased hematocrit and erythrocyte count in another study in rats. Chronic ingestion of methyl parathion induced reduction of mean hemoglobin, hematocrit, and erythrocyte eounts in rats. 

No acute oral MRL was derived for methyl parathion because data regarding the most sensitive effect that was observed after acute oral exposure are conflicting. Increased pup mortality and altered behavior occurred in offspring of rats exposed to 1 mg/kg/day methyl parathion during, but no effects on pup survival or on sensitive electrophysiological indices of neurotoxicity were seen at virtually the same dose, 0.88 mg/kg/day, in a similar developmental toxicity study. 

An MRL of 0.0007 mg/kg/day has been derived for intermediate-duration oral exposure (15-364 days) to methyl parathion. 

Death from a combination of inhalation and dermal exposures has been reported by Fazekas (1971) in four individuals who used methyl parathion (Wofatox) spray in a careless manner. These individuals were part of a larger series of 30 cases (20 men, 10 women) of fatal methyl parathion intoxication reported by Fazekas (1971). Since 26 of these fatalities followed oral exposure, this report is discussed in detail in Sections 3.2.2.1 and 3.2.2.2. 

There have been a number of cases of human intoxication and death from oral exposure to methyl parathion. 

Hematological Effects. No studies were located regarding hematological effects in humans after oral exposure to methyl parathion. 

Ocular Effects. One study reported that seven children exposed to methyl parathion by inhalation, oral, and possibly dermal routes exhibited pinpoint pupils (miosis) (Dean et al. 1984). This effect is a consequence of the effects on the parasympathetic nervous system. No other studies were located regarding ocular effects in humans after oral exposure to methyl parathion. 

LD50 values for the dermal route of exposure to methyl parathion have been established in acute studies for rats 67 mg/kg for males and females (Gaines 1960), 110 mg/kg for males, and 120 mg/kg for females (EPA 1978e). The LD50 in male mice exposed by dermal application of methyl parathion to their hind feet (rather than shaved backs) was 1,200 mg/kg (Skinner and Kilgore 1982a). The mice were muzzled to prevent oral exposure from grooming. 

Mouse/oral exposure drinking water Chromosomal aberrations - Degraeve et al. 1985... 

Mouse/oral exposure gavage Sperm shape abnormalities + Mathew et al. 1992... 

Human lymphocytes/oral exposure Chromosomal aberrations + Van Bao et al. 1974... 

The available data are insuiScient to determine the pattern or extent of distribution in human tissues after oral exposure to this compound. 

Limited information was available regarding excretion in humans after oral exposure to methyl parathion. During 5 days of exposure of four subjects to 2 or 4 mg of methyl parathion once daily in food (0.028 or... 

The available evidence suggests that excretion of methyl parathion metabolites in humans and animals following acute oral exposure is essentially the same and occurs rapidly. Excretion occurs primarily via the urine. Methyl parathion can also be excreted in breast milk, although it has been detected only in a limited number of samples from women of central Asia, for which exposure data were not available (Lederman 1996) (see also Section 3.4.2.2). A study in rats also reported excretion of methyl parathion in the milk (Golubchikov 1991 Goncharuk et al. 1990). 

Data from a single study in dogs suggest that hepatic first-pass metabolism may limit systemic availability of the parent compound following oral exposure (Braeckman et al. 1983). Placental transfer of methyl parathion was demonstrated in pregnant rats 1-3 days before parturition. Thirty minutes after administration, both methyl parathion and methyl paraoxon were found in fetal brain, liver, and muscle methyl parathion, but not methyl paraoxon, was detected in placenta and maternal liver (Ackermann and Engst 1970). Methyl parathion binds reversibly to serum albumin, but is readily distributed to the tissues (Braeckman et al. 1980, 1983). 

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