Toxicological studies with dithranol and its 10-acyl analogues

P. Männistö, D. Kirkland, M. Viluksela, Leena Tikkanen

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7 Citations (Scopus)

Abstract

The oral LD50 values of an antipsoriatic drug, dithranol, were 1542 mg/kg in NMRI mice and 3216 mg/ kg in Wistar rats. Three 10-acyl analogues of dithranol (10-acetyl, 10-propionyl and 10-butyryl dithranol or butantrone) were more toxic both in mice and rats. They were mutagenic only in TA1537 of the five Salmonella typhimurium strains tested. None of them were mutagenic in two Escherichia coli strains. Butantrone was least toxic to test bacteria and had the lowest mutagenic activity on TA1537. In metaphase analysis of in vitro treated human lymphocytes, dithranol, 10-acetyl dithranol and 10-propionyl dithranol produced significant increases in the number of chromosome and chromatid gaps but without a clear dose-response relationship, and without inducing significant breaks. Butantrone did not cause significant increases in gaps or breaks. In the mouse micronucleus test, dithranol and butantrone caused no increases in micronucleated polychromatic or normochromatic erythrocytes, indicating lack of clastogenic activity in vivo at maximum tolerated doses. Hence, dithranol and its 10-acyl analogues have a weak mutagenic activity in vitro. The mutagenic activity of butantrone is lower than that of the other analogues and dithranol.

Original languageEnglish
Pages (from-to)180 - 185
Number of pages6
JournalArchives of Toxicology
Volume59
Issue number3
DOIs
Publication statusPublished - 1986
MoE publication typeNot Eligible

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Anthralin
Toxicology
Poisons
Rats
Micronucleus Tests
Chromatids
Salmonella
Maximum Tolerated Dose
Lymphocytes
Lethal Dose 50
Salmonella typhimurium
Metaphase
Chromosomes
Escherichia coli
butantrone
Wistar Rats
Bacteria
Erythrocytes
Pharmaceutical Preparations

Cite this

Männistö, P., Kirkland, D., Viluksela, M., & Tikkanen, L. (1986). Toxicological studies with dithranol and its 10-acyl analogues. Archives of Toxicology, 59(3), 180 - 185. https://doi.org/10.1007/BF00316330
Männistö, P. ; Kirkland, D. ; Viluksela, M. ; Tikkanen, Leena. / Toxicological studies with dithranol and its 10-acyl analogues. In: Archives of Toxicology. 1986 ; Vol. 59, No. 3. pp. 180 - 185.
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Männistö, P, Kirkland, D, Viluksela, M & Tikkanen, L 1986, 'Toxicological studies with dithranol and its 10-acyl analogues', Archives of Toxicology, vol. 59, no. 3, pp. 180 - 185. https://doi.org/10.1007/BF00316330

Toxicological studies with dithranol and its 10-acyl analogues. / Männistö, P.; Kirkland, D.; Viluksela, M.; Tikkanen, Leena.

In: Archives of Toxicology, Vol. 59, No. 3, 1986, p. 180 - 185.

Research output: Contribution to journalArticleScientificpeer-review

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N2 - The oral LD50 values of an antipsoriatic drug, dithranol, were 1542 mg/kg in NMRI mice and 3216 mg/ kg in Wistar rats. Three 10-acyl analogues of dithranol (10-acetyl, 10-propionyl and 10-butyryl dithranol or butantrone) were more toxic both in mice and rats. They were mutagenic only in TA1537 of the five Salmonella typhimurium strains tested. None of them were mutagenic in two Escherichia coli strains. Butantrone was least toxic to test bacteria and had the lowest mutagenic activity on TA1537. In metaphase analysis of in vitro treated human lymphocytes, dithranol, 10-acetyl dithranol and 10-propionyl dithranol produced significant increases in the number of chromosome and chromatid gaps but without a clear dose-response relationship, and without inducing significant breaks. Butantrone did not cause significant increases in gaps or breaks. In the mouse micronucleus test, dithranol and butantrone caused no increases in micronucleated polychromatic or normochromatic erythrocytes, indicating lack of clastogenic activity in vivo at maximum tolerated doses. Hence, dithranol and its 10-acyl analogues have a weak mutagenic activity in vitro. The mutagenic activity of butantrone is lower than that of the other analogues and dithranol.

AB - The oral LD50 values of an antipsoriatic drug, dithranol, were 1542 mg/kg in NMRI mice and 3216 mg/ kg in Wistar rats. Three 10-acyl analogues of dithranol (10-acetyl, 10-propionyl and 10-butyryl dithranol or butantrone) were more toxic both in mice and rats. They were mutagenic only in TA1537 of the five Salmonella typhimurium strains tested. None of them were mutagenic in two Escherichia coli strains. Butantrone was least toxic to test bacteria and had the lowest mutagenic activity on TA1537. In metaphase analysis of in vitro treated human lymphocytes, dithranol, 10-acetyl dithranol and 10-propionyl dithranol produced significant increases in the number of chromosome and chromatid gaps but without a clear dose-response relationship, and without inducing significant breaks. Butantrone did not cause significant increases in gaps or breaks. In the mouse micronucleus test, dithranol and butantrone caused no increases in micronucleated polychromatic or normochromatic erythrocytes, indicating lack of clastogenic activity in vivo at maximum tolerated doses. Hence, dithranol and its 10-acyl analogues have a weak mutagenic activity in vitro. The mutagenic activity of butantrone is lower than that of the other analogues and dithranol.

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