30-day oral toxicity study of domoic acid in cynomolgus monkeys: lack of overt toxicity at doses approaching the acute toxic dose.
Domoic acid was orally administered to 3 cynomolgus monkeys at doses of 0.5 mg/kg for 15 days and then at 0.75 mg/kg for another 15 days. After the 30-day dosing period, the treated monkeys were killed. Parameters monitored as markers for toxicity included body weight, food and water consumption, clinical observations, hematology, serum chemistry, light microscopy of all major organs (including brain and retina), and glial fibrillary acid protein immunohistochemistry. Domoic acid in serum and 24-hour urine samples was measured at several time points. All parameters measured remained unremarkable. Domoic acid concentrations measured in the 24-hour urine samples indicated that gastrointestinal absorption in the monkey was approximately 4-7 percent of the administered dose, which is at least twice that previously reported for the rat.
Truelove
J
J
Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Sir F.G. Banting Research Centre, Ottawa, Canada. john_truelove@i5dtep3.hwc.ca
Mueller
R
R
Pulido
O
O
Martin
L
L
Fernie
S
S
Iverson
F
F
D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007608:Kainic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D008252:Macaca fascicularis; D009467:Neuromuscular Depolarizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D013997:Time Factors
D009467:Neuromuscular Depolarizing Agents; C012301:domoic acid; D007608:Kainic Acid