Clinical Effects and Plasma Concentration Determination After 2,4-Dichlorophenoxy-acetic Acid 200 mg/kg Administration in the Dog

Abstract

Objective: To investigate the clinical effects and to determine the 2,4-dichlorophenoxyacetic acid plasma concentrations after a dose of twice the reported LD₅₀ (100 mg/kg) was administered orally to dogs. Investigation included electromyographic evaluations and biochemical parameter determinations, as well as observable clinical signs. Methods: Six beagle dogs were administered 2,4-dichlorophenoxyacetic acid 200 mg/kg orally. Dogs were monitored for the development of clinical signs and were anesthetized at 24 hours for needle electromyography. Blood was collected pre- and 24-hours postadministration. Plasma was analyzed for total and unbound 2,4-dichlorophenoxyacetic acid by high-performance liquid chromatography with fluorescence detection. Serum was submitted for clinical chemistry parameter analysis. Statistical analyses of the chemistry parameters were performed using paired t-tests. Results: All 6 dogs survived after oral administration of twice the reported LD₅₀. Clinical signs observed were vomiting in 33% and diarrhea in 100% of the dogs. No gait abnormalities were seen in awake dogs. Electromyographic findings revealed predominantly insertional myotonia with 1 dog having spontaneous fibrillations. Decreases from baseline measurements were seen in serum calcium, potassium, and total bilirubin. The mean total and unbound plasma 2,4-dichlorophenoxyacetic acid concentrations were 511 mg/L and 129 mg/L, respectively. Conclusions: This study demonstrates that the beagle dog is less sensitive to the acute effects of 2,4-dichlorophenoxyacetic acid than previously reported. The main clinical effects seen after oral administration of twice the reported LD₅₀ were vomiting and diarrhea. Total and unbound plasma 2,4-dichlorophenoxyacetic acid concentrations may be a useful indicator of toxicity.