1994; Ehrich and Jortner, 2001; Gallo and Lawryk, 1991; Johnson and Glynn, 2001; Kamrin, 1997; Lotti, 2001; Richardson, 1995).

Other delayed effects. Some studies have reported other persistent symptoms after poisoning with organophosphorous compounds or symptoms that appear 5–10 years after a poisoning episode, including neurologic and visual deficits, behavioral alterations, and impairment of cognition. Those effects, however, might be confounded by other factors or be the result of inappropriate study designs (Abou-Donia, 1995; Baker and Wilkinson, 1990; Chambers and Levi, 1992; Ecobichon and Joy, 1994; Eyer, 1995; Gallo and Lawryk, 1991; Jamal, 1997; Kaloianova and El Batawi, 1991; Lotti, 2001). Although some latent effects have been noted in laboratory rats, the symptoms reported in people have been difficult to verify in animal studies partly because of difficulties in replication of exposures and extrapolation of end points from humans to animals (Ballantyne and Marrs, 1992; Bushnell et al., 1993; Ecobichon and Joy, 1994; Gallo and Lawryk, 1991; Marrs, 1996; Mattsson et al., 1996; Maurissen et al., 2000).

Experimental Data

Neurotoxic Effects

As noted above, organophosphorous insecticides increase levels of the neurotransmitter acetylcholine in both the central and peripheral nervous systems. Excess acetylcholine at neuromuscular junctions causes excessive neuromuscular stimulation (such as tremors), which can be followed by neuromuscular block. Excess acetylcholine at synapses of the autonomic nervous system affects quantity of secretions, heart rate, blood pressure, gastrointestinal function, urination, and pupil size. Excess acetylcholine at synapses of the CNS can alter behavior and cognition. Studies in animals generally require substantial inhibition of acetylcholinesterase (for example, greater than 40% inhibition of erythrocyte acetylcholinesterase) before those effects are seen. Even when doses of organophosphorous compounds are sufficient to cause notable evidence of cholinergic poisoning in animals or people, it is unusual for signs and symptoms to continue after recovery of acetylcholinesterase activity (Ballantyne and Marrs, 1992; Cecchine et al., 2000; Chambers and Levi, 1992; Ecobichon, 2001; Ecobichon and Joy, 1994; Eyer, 1995; Gallo and Lawryk, 1991; Marrs, 1996; Mattsson et al., 1996).

There has also been discussion around the potential effects of organophosphorous compounds on learning and memory following fetal and childhood exposures. In animals, however, some experiments have not demonstrated an increased sensitivity during the developing periods. Mattsson and colleagues (2000) treated rats with chlorpyrifos (0.3, 1.0, and 5.0 mg/kg/day) from gestational day 6 to postnatal day 10 and measured chlorpyrifos concentrations and cholinesterase inhibition in the fetuses and the dams. The nursing pups had a lower concentration than the dams and cholinesterase activity in all tissues of the high-dose pups rapidly returned to near control levels. Another study in rats with the same dosing regimen examined learning and memory, but no effects were seen in the absence of maternal toxicity (Maurissen et al., 2000).

Animal studies have been conducted to assess the persistence of neurotoxic effects of organophosphorous compounds. The results of a study of chlorpyrifos (at 1, 3, and 10 mg/kg per day, 5 days/week for 4 weeks followed by 4 weeks of recovery) do not indicate effects on short-term memory in adult rats, but do indicate a decrease in motor activity (Maurissen

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