Organophosphates animal exposures

Developmental Effects. Adverse effects of methyl parathion on hirman fetal development have not been reported. Based on studies in animals, such effects appear to be possible if pregnant women were exposed during the first trimester to high concentrations of methyl parathion that resulted in significant depression of cholinesterase levels, particularly if concomitant signs and symptoms of organophosphate intoxication occur. Such an exposure scenario may occur with occupational exposure, exposure in homes or offices illegally sprayed with methyl parathion, or accidental exposure to methyl parathion, but is less likely as a result of low-level exposure. 

Following exposure of humans to organophosphates, but not specifically methyl parathion, restoration of plasma cholinesterase occurs more rapidly than does restoration of erythrocyte cholinesterase (Grob et al. 1950 Midtling et al. 1985). These findings are supported by studies of methyl parathion in animals. Erythrocyte cholinesterase levels are representative of acetylcholinesterase levels in the nervous system, and, therefore, may be a more accurate biomarker of the neurological effects of chronic low level exposure of humans to methyl parathion (Midtling et al. 1985 NIOSH 1976). 

Several organophosphate ester hydraulic fluids have produced neurological effects in several animal species after intermediate inhalation exposure (see Table 2-2). 

No information was located regarding neurological effects in animals after chronic inhalation exposure to organophosphate ester hydraulic fluids. 

No studies were located regarding developmental effects in humans or animals after inhalation exposure to mineral oil hydraulic fluids, organophosphate ester hydraulic fluids, or polyalphaolefin hydraulic fluids. 

Many of the studies on the neurological effects of oral exposure to organophosphate ester hydraulic fluids in animals have employed chickens as models instead of the more commonly used rodent models. For reasons that are not well understood, organophosphate-induced delayed neuropathy can be induced in chickens and cats, but not in mice or rats (Abou-Donia and Lapadula 1990). 

Several animal studies conducted histological examination of the heart following intermediate-duration dermal exposure to organophosphate ester hydraulic fluids. No cardiovascular effects were observed in rats exposed to 5,750 mg/kg/day of Fyrquel 220 (MacEwen and Vemot 1983), or rabbits exposed to 1,000 mg/kg/day of cyclotriphosphazene (Kinkead et al. 1989c, 1990) or an unspecified amount of Cellulube 220 (Carpenter et al. 1959). 

No studies were located that examined the toxicokinetics of mineral oil, organophosphate ester, or polyalphaolefin hydraulic fluids in humans or animals, with the exception of a study examining absorption in rats after exposure to a hydraulic fluid containing 99.9% cyclotriphosphazene (Kinkead and Bashe 1987) and the absorption and metabolism of Reolube HYD46, another organophosphate hydraulic fluid (Ciba-Geigy 1985). This section, therefore, discusses available information on the toxicokinetics of major components of these classes of hydraulic fluids or of materials that maybe expected to display similar toxicokinetic properties based on similar physical and chemical characteristics. It should be emphasized that many hydraulic fluids are complex mixtures of chemicals that may include some chemicals which may not share toxicokinetic properties with the major components. 

No data were located regarding absorption in animals after inhalation exposure to organophosphate ester hydraulic fluids or specific organophosphate esters, except for the observation that parent material was not detected by gas chromatography in the blood or urine of male rats exposed to 5,120 mg/m3 of an aerosol of a cyclotriphosphazene (99.9%) hydraulic fluid for 4 hours, thereby suggesting that the extent of absorption was limited (Kinkead and Bashe 1987). Blood samples were collected at 0, 24, and 48 hours after exposure was terminated. Urine was collected for 24 hours after exposure. 

The lack of corroborative case reports, epidemiological data, or animal data (see next paragraph) makes the association between dermal exposure to mineral oil hydraulic fluids and peripheral neuropathy uncertain. Nonetheless, the presence of organophosphate esters, some of which are demonstrated neurotoxic agents, in most mineral oil hydraulic fluids (they often are added as anti-wear agents) suggests that they may play a causative role if such an association exists. 

In conclusion, the limited animal and human data suggest that acute to intermediate exposures to mineral oil hydraulic fluids do not represent a major hazard to the neurological health of workers or the general public. The possible presence of low levels of neurotoxic organophosphate esters in these fluids, however, may lead to some concern to limit exposure. 

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