Propanil-induced methemoglobinemia and hemoglobin binding in the rat

David C McMillan, Tammie A. McRae, Jack A. Hinson

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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-dichloroaniline. 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.

Original languageEnglish (US)
Pages (from-to)503-507
Number of pages5
JournalToxicology and Applied Pharmacology
Volume105
Issue number3
DOIs
StatePublished - Sep 15 1990

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Propanil
Methemoglobinemia
Rats
Hemoglobins
Methemoglobin
Metabolites
Sulfinic Acids
High Pressure Liquid Chromatography
Oxyhemoglobins
Proteins
Amides
Liver
Cysteine
Sprague Dawley Rats
Toxicity
Erythrocytes

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Propanil-induced methemoglobinemia and hemoglobin binding in the rat. / McMillan, David C; McRae, Tammie A.; Hinson, Jack A.

In: Toxicology and Applied Pharmacology, Vol. 105, No. 3, 15.09.1990, p. 503-507.

Research output: Contribution to journalArticle

McMillan, David C ; McRae, Tammie A. ; Hinson, Jack A. / Propanil-induced methemoglobinemia and hemoglobin binding in the rat. In: Toxicology and Applied Pharmacology. 1990 ; Vol. 105, No. 3. pp. 503-507.
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abstract = "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-dichloroaniline. 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.",
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