Subchronic inhalation toxicity of diglyme

Diglyme [1,1'-oxybis(2-methoxyethane)] is an organic solvent belonging to t he glycol ether class of compounds. To assess the inhalation toxicity of di glyme, groups of 20 male and 10 female rats were exposed by nose-only inhal ation 6 hours/day, 5 days/week for 2 weeks to either 0 (control), 110, 370 or 1100 ppm diglyme. To compare potency, 2-methoxyethanol was also tested a t 300 ppm. Rats were sacrificed either immediately following exposure, afte r a 14-day recovery period, or after 42 and 84 days of recovery (males only ). Parameters investigated included in-life observations and body weights, clinical pathology, and histopathology with organ weights. Exposure to digl yme produced a variety of concentration-related haematological, clinical ch emical and histopathological changes in both sexes. The most striking effec t produced in all test groups was cellular injury involving the testes, sem inal vesicles, epididymides and prostate. Although these effects were more severe at the higher concentrations tested, partial or complete recovery wa s seen by 84 days post-exposure. Changes in the haematopoietic system occur red in both sexes and involved the bone marrow, spleen, thymus, leucocytes and erythrocytes. The testicular effects of diglyme were somewhat less pron ounced than those seen with 2-methoxyethanol. The no-observed-effect level (NOEL) for repeated inhalation exposure to diglyme in female rats is 370 pp m. For males, all concentrations tested produced effects to the reproductiv e system, hence a no-observed-effect level could not be demonstrated. (C) 1 998 Published by Elsevier Science Ltd. All rights reserved.