A neuromuscular screen for use in industrial toxicology

A short objective screening technique has been developed to identify those agents that have peripheral and/or central nervous effects in small laboratory rodents (when utilized as a feature in routine testing protocols). The technique initially utilizes a series of simple quantitative and qualitative measures of various aspects of sensory and motor function. The methodology has been designed for and utilized as modular additions in a large number and variety of toxicity studies performed on industrial compounds including macrocyclic ethers, aldehydes, urethane foam catalysts, and others. It is shown to be a more sensitive early indicator of toxicity than such classical measures as body weight or clinical chemistry in those cases (such as the macrocyclic ethers and amino propionitrile) where the nervous or muscular system are the ultimate target organs. It is also a noninvasive and relatively inexpensive methodology. The second phase (a series of isolated tissue assays) establishes the ability to differentiate between reversible (pharmacologic) and irreversible (toxicologic) sensory-neural responses. The development and validation of the procedure have involved its use in both acute and subchronic studies by the inhalation, oral, ip, and sc routes. As necessary, isolated tissue and biochemical assays have been done to verify mechanisms of action. In fact, decision-tree schemes have been developed as part of the screen. These schemes allow elucidation of mechanisms of action if such is desired and statistical evaluation of the diverse data generated.