Inhalation toxicity of Dioxole and Dioxolane compounds in the rat

Citation
Gl. Kennedy et al., Inhalation toxicity of Dioxole and Dioxolane compounds in the rat, DRUG CHEM T, 24(1), 2001, pp. 1-17
Citations number
13
Categorie Soggetti
Pharmacology & Toxicology
Journal title
DRUG AND CHEMICAL TOXICOLOGY
ISSN journal
01480545 → ACNP
Volume
24
Issue
1
Year of publication
2001
Pages
1 - 17
Database
ISI
SICI code
0148-0545(2001)24:1<1:ITODAD>2.0.ZU;2-0
Abstract
Four chemicals (Dioxole 418, Dioxolane 418, Dioxolane 416 and Dioxolane 456 ) which are used as stabilizers in highresolution image were tested or both their acute and repeated inhalation toxicity in the rat using nose-only ex posures. Acute studies determined the lethal concentrations following a sin gle 4-hour exposure, repeated exposure inhalation studies determined the po tency and target tissue(s) following 6-hour/day exposures, 5 days/week for 2 weeks. Each of the chemicals was at least mildly toxic acutely with appro ximate lethal concentrations of > 1,500 ppm for Dioxole 418, 1,300 ppm for Dioxolane 418, 1,700 ppm for Dioxolane 416, and 4,300 ppm for Dioxolane 456 . No specific unusual clinical signs of response were seen in the rats expo sed acutely. Repeated exposures with Dioxole 418 and Dioxolane 418 resulted in no evidence of toxicity with NOAEL's being 440 and 500 ppm respectively (the highest concentrations tested). Repeated exposures to 250 ppm Dioxola ne 456 were not tolerated with mortalities observed after exposure. Severe bone marrow hypoplasia along with reductions in platelet and neutrophil cou nts were observed at this concentration with less severe hemopoietic change s seen also at 10 and 51 ppm. The no-effect level for Dioxolane 456 was det ermined to be 10 ppm in female rats and I ppm in males. The same hemopoieti c effects were seen with Dioxolane 416 at exposures of 53 ppm or greater in males but not in females exposed to 53 ppm Dioxolane 416. Hepatocellular h ypertrophy and depression of serum alkaline phosphatase activity were seen in male rats exposed to 500 but not 53 ppm Dioxolane 416. Testicular degene ration was also seen in rats exposed to 500 ppm Dioxolane 416. The NOAEL wa s 5 ppm for the chemical.