Administration of [ring-U-14C]
propanil (3,4-dichloropropionanilide) to male Sprague-Dawley rats (30, 100, and 300 mg/kg, ip) increased the formation of
methemoglobin at the two highest doses. Following a
propanil dose of 100 mg/kg,
methemoglobin formation attained a maximum level of 5% by 1.5 hr and declined to normal levels (approximately 2.5%) by 12 hr.
Hemoglobin binding attained a maximum level of 50 pmol/mg
protein by 12 hr, and remained constant for 24 hr. Following a
propanil dose of 300 mg/kg,
methemoglobin formation attained a maximum level of 24% by 4.5 hr, and declined to a level of 5% by 24 hr.
Hemoglobin binding attained a maximum level of 425 pmol/mg
protein by 12 hr, and remained constant for 24 hr.
Hemoglobin binding was also detected at the lowest
propanil dose (10 pmol/mg
protein) even though
methemoglobin formation was not observed. HPLC analysis of alkaline-treated
hemoglobin from
propanil-treated rats indicated the presence of one radiolabeled compound with the same HPLC retention time as 3,4-dichloraniline. These data are consistent with the concept that
propanil is converted to
N-hydroxy-3,4-dichloroaniline in the liver. Subsequently, this metabolite enters the erythrocyte and is oxidized by
hemoglobin to 3,4-dichloronitrosobenzene with concomitant conversion of
oxyhemoglobin to
methemoglobin. The 3,4-dichloronitrosobenzene binds to
cysteine residues on
hemoglobin as the corresponding sulfinic
acid amide adduct. These data suggest that human exposure to
propanil may be monitored in the absence of observable toxicity by the analysis of
propanil metabolites bound to
hemoglobin.