Inhalation toxicity of Dioxole and Dioxolane compounds in the rat.
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 exposures. Acute studies determined the lethal concentrations following a single 4-hour exposure; repeated exposure inhalation studies determined the potency 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 approximate 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 exposed 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 Dioxolane 456 were not tolerated with mortalities observed after exposure. Severe bone marrow hypoplasia along with reductions in platelet and neutrophil counts were observed at this concentration with less severe hemopoietic changes seen also at 10 and 51 ppm. The no-effect level for Dioxolane 456 was determined to be 10 ppm in female rats and I ppm in males. The same hemopoietic 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 hypertrophy and depression of serum alkaline phosphatase activity were seen in male rats exposed to 500 but not 53 ppm Dioxolane 416. Testicular degeneration was also seen in rats exposed to 500 ppm Dioxolane 416. The NOAEL was 5 ppm for the chemical.
Kennedy
G L
GL
Haskell Laboratory for Toxicology, DuPont Company, 1090 Elkton Road, Newark, DE 19714, USA.
O'Neill
A J
AJ
Valentine
R
R
D000280:Administration, Inhalation; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D004148:Dioxolanes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004149:Dioxoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009043:Motor Activity; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D016273:Occupational Exposure; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D023382:Toxicity Tests, Acute
D004148:Dioxolanes; D004149:Dioxoles; D009153:Mutagens; D000469:Alkaline Phosphatase