Behavioral Toxicology of Volatile Organic Solvents V. Comparisons of the Behavioral and Neuroendocrine Effects Among n-Alkanes

Abstract

Four homologous n-alkanes were compared for their ability to impair performance and stimulate hypothalamic-pituitary activity in mice. Performance was assessed using operant responding maintained under a fixed interval 60-sec schedule of milk presentation. Cumulative concentration-effect functions for octane, heptane, hexane, and pentane were obtained by incrementally increasing exposure concentrations until responding was abolished. Recovery from these rate-decreasing effects was determined 30 min after exposure to the highest concentration. Rate-decreasing potency (EC₅₀) was greatest for octane (2474 ppm), and progressively less for heptane (3872 ppm), hexane (7051 ppm), and pentane (36130 ppm). Responding recovered completely 30 min after exposure for pentane and hexane, to 75% of pre-exposure levels for heptane, but to only 15% of pre-exposure levels for octane. The risk of obtaining a small effect with these agents (the concentration expected to decrease performance 10% in 1 out of 1000 mice) exhibited a similar order. The effect was predicted to occur at 227 ppm for octane, 331 ppm for heptane, and 1429 ppm for pentane. However, this prediction occurred at an unusually low dose for hexane (68 ppm). These n-alkanes also stimulated up to 2000-fold increases in adrenocorticotropin hormone (ACTH) release. n-Hexane was slightly more potent and produced larger effects. These studies demonstrate a direct relationship between aliphatic carbon chain length and the potency of n-alkanes in impairing performance.