Abstract

OBJECTIVES: Despite observation of adverse reproductive effects of toluene, including alterations of serum gonadotropins (luteinising hormone (LH) and follicle stimulating hormone (FSH)) in humans, little is known of the mechanism of toxicity. The hypothesis was tested that toluene acutely suppresses pulsatile gonadotropin secretion by measuring LH and FSH at frequent intervals during controlled exposure to toluene. METHODS: Women in the follicular and luteal phases of the menstrual cycle and men were randomised to inhale filtered air with or without 50 ppm toluene through a mouthpiece for 3 hours (19% of the OSHA permissible exposure limit). Blood was sampled by intravenous catheter at 20 minute intervals for 3 hours before, 3 hours during, and 3 hours after exposure. Plasma LH, FSH, and testosterone were measured. Pulse amplitude, pulse frequency, and mean concentrations of LH and FSH for each of the 3 hour periods before, during and after exposure to toluene versus sham exposure were calculated with the ULTRA pulse detection program and compared by analysis of variance (ANOVA) with repeated measures. RESULTS: In men mean concentrations of LH showed a significant interaction (p < 0.05) between exposure and sampling period, with a greater LH decline during exposure to toluene than sham exposure. However, there was no concomitant effect on testosterone concentrations. The LH pulse frequency of women in the luteal phase showed a trend towards a significant interaction between exposure and sampling period (p = 0.06), with a greater decline in pulse frequency during exposure to toluene than sham exposure. There were no other significant effects of exposure to toluene. CONCLUSIONS: Three hour exposure to 50 ppm toluene did not result in abnormal episodic LH or FSH secretion profiles, however, subtle effects on LH secretion in men and women in the luteal phase were found. The clinical relevance of these effects is unclear, indicating the need for further study of reproductive function in exposed workers.