Decreased pup weight and increased pup mortality were reported after administration of chlorpyrifos to rats. That occurred when pregnant female rats were exposed to chlorpyrifos at doses that caused maternal toxicity. Acetylcholinesterase inhibition was indicated by excessive salivation and tremors (Breslin et al., 1996). Decreased pup weight and increased pup mortality have also been reported in rats exposed to acetylcholinesterase-inhibiting doses of chlorpyrifos between birth and weaning (Carr et al., 2001). Biochemical changes other than acetylcholinesterase inhibition have been reported in neonatal rats exposed to chlorpyrifos, including changes in protein synthesis, DNA synthesis, intracellular signaling, and cholinergic receptors (Dam et al., 1998; Song et al., 1997; Tang et al., 1999; Whitney et al., 1995). Changes in righting reflex, cliff avoidance, locomotor activity, and spatial learning have been reported in neonatal, weanling, and juvenile rats exposed to chlorpyrifos at doses expected to inhibit acetylcholinesterase activity; some detriments occurred without notable enzyme inhibition or continued after substantial recovery of esterase activity (Carr et al., 2001; Chanda and Pope, 1996; Jett et al., 2001). The significance of behavioral changes in young rats with regard to possible toxicity in adult animals or in other species is unknown.

Immunotoxic Effects

The modulation of the immune system by malathion and its impurities depends on the dose, specific agent, cellular target, and duration of exposure; both stimulatory and suppressive effects have been reported in exposed animals. Dichlorvos has been reported to have suppressive effects on the generation of macrophages on chronic exposure and the ability to suppress cellular and humoral immune responses at cholinergic doses (Rodgers, 2001).

Other Health Effects

Dermatitis and hypersensitivities, including bronchospasm, have been reported after exposure to organophosphorous insecticides. The contributions of contaminants and vehicles to those responses have not been differentiated from effects of the active ingredients alone. Transient effects of malathion and dichlorvos on the immune system, including hypersensitivity and dermatitis, have been reported (Baker and Wilkinson, 1990; Chambers and Levi, 1992; Gallo and Lawryk, 1991; Kaloianova and El Batawi, 1991). Chlorpyrifos has been reported to increase lymphocyte numbers (Richardson, 1995).

Effects on respiratory, cardiac, and gastrointestinal systems in humans and animals are related to the ability of the insecticides to inhibit acetylcholinesterase and increase acetylcholine-mediated neural transmission (Ballantyne and Marrs, 1992). Some organophosphorous compounds—but not the insecticides used in the Gulf War—have been reported to have endocrine effects, including dysregulation of hypothalamic releasing factors when acetylcholinesterase was substantially inhibited (Smallridge et al., 1991), decreased spermatogenesis (Somkuti et al., 1991), increased estrogen metabolism (Berger and Sultatos, 1997), and antagonism at androgen receptors (Tamura et al., 2001).

Interactions with Other Agents

Organophosphorous insecticides can inhibit esterases other than acetylcholinesterase, including pseudocholinesterase and carboxylesterases in both humans and animals.

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