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 64mg benzocaine hydrochloride per kg bw and then euthanized at intervals up to 120min. Plasma levels of benzocaine were relatively low at all times, whereas methemoglobin peaked at 24min. Additional rats were orally gavaged with 0-1024mg benzocaine hydrochloride per kg bw and euthanized after 24min. Plasma levels of benzocaine increased from 0.01μM at 2mg per kg bw to 2.9μM at 1024mg per kg bw. Methemoglobin levels did not differ from controls at doses up to 32mg per kg bw in females and 64mg per kg bw in males, whereupon the value increased to ∼80% at 1024mg 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.