Clinical effects and plasma concentration determination after 2,4-dichlorophenoxy-acetic acid 200 mg/kg administration in the dog

Objective: To investigate the clinical effects and to determine the 2,4-dic hlorophenoxyacetic acid plasma concentrations after a dose of twice the rep orted LD50 (100 mg/kg) was administered orally to dogs. Investigation inclu ded electromyographic evaluations and biochemical parameter determinations, as well as observable clinical signs. Methods: Six beagle dogs were admini stered 2,4-dichlorophenoxyacetic acid 200 mg/kg orally. Dogs were monitored for the development of clinical signs and were anesthetized at 24 hours fo r needle electromyography. Blood was collected pre- and 24-hours postadmini stration. Plasma was analyzed for total and unbound 2,4-dichlorophenoxyacet ic acid by high-performance liquid chromatography with fluorescence detecti on. Serum was submitted for clinical chemistry parameter analysis. Statisti cal analyses of the chemistry parameters were performed using paired t-test s. Results: All 6 dogs survived after oral administration of twice the repo rted LD50. Clinical signs observed were vomiting in 33% and diarrhea in 100 % of the dogs. No gait abnormalities were seen in awake dogs. Electromyogra phic findings revealed predominantly insertional, myotonia with 1 dog havin g spontaneous fibrillations. Decreases from baseline measurements were seen in serum calcium, potassium, and total bilirubin. The mean total and unbou nd plasma 2,4-dichlorophenoxyacetic acid concentrations were 511 mg/L and 1 29 mg/L, respectively. Conclusions: This study demonstrates that the beagle dog is less sensitive to the acute effects of 2,4-dichlorophenoxyacetic ac id than previously reported. The main clinical effects seen after oral admi nistration of twice the reported LD50 were vomiting and diarrhea. Total and unbound plasma 2,4-dichlorophenoxyacetic acid concentrations may be a usef ul indicator of toxicity.