Benzocaine-induced methemoglobinemia in an acute-exposure rat model

Tricaine methanesulfonate, a sedative for temporarily immobilizing fish, has a 21-day withdrawal time. Benzocaine has been proposed as an alternative sedative because a withdrawal period may not be required. Since benzocaine is known to induce methemoglobinemia, the potential for orally administered benzocaine to induce methemoglobin was assessed in rats. Sprague–Dawley rats were given a single gavage administration of 64 mg benzocaine hydrochloride per kg bw and then euthanized at intervals up to 120 min. Plasma levels of benzocaine were relatively low at all times, whereas methemoglobin peaked at 24 min. Additional rats were orally gavaged with 0–1024 mg benzocaine hydrochloride per kg bw and euthanized after 24 min. Plasma levels of benzocaine increased from 0.01 μM at 2 mg per kg bw to 2.9 μM at 1024 mg per kg bw. Methemoglobin levels did not differ from controls at doses up to 32 mg per kg bw in females and 64 mg per kg bw in males, whereupon the value increased to ∼80% at 1024 mg per kg bw. These data were used to estimate the potential impact of benzocaine residues in fish and suggest that the consumption of fish treated with benzocaine hydrochloride will not cause methemoglobinemia in humans.