Evaluation of the genotoxicity of the imidazole antifungal climbazole: Comparison to published results for other azole compounds

Pérez-Rivera, Alex A.; Hu, Ting; Aardema, Marilyn J.; Nash, J.F.

doi:10.1016/j.mrgentox.2008.09.011

Cited by 22 publications

(8 citation statements)

References 23 publications

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“…Climbazole is used in cosmetics as an antimycotic preservative and especially as an active ingredient of antidandruff hair care formulations up to a maximum content of 2.0%, equivalent to approximately 15 g/L in antidandruff shampoos [8]. Products containing climbazole are widely available in many countries, for example, in Western Europe and China [9]. Climbazole belongs to the group of imidazole fungicides and inhibits the biosynthesis of ergosterol, the major component of fungal plasma membranes, by noncompetitively blocking the active site of the enzyme lanosterol 14a-demethylase, also known as fungal CYP51 [10].…”

Section: Introductionmentioning

confidence: 99%

Ecotoxicity of climbazole, a fungicide contained in antidandruff shampoo

Richter

Wick

Ternes

et al. 2013

Environmental Toxicology and Chemistry

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Emerging pollutants such as personal care products can reach the environment via effluents from wastewater treatment plants (WWTPs) and digested sludge. Only recently, the antidandruff agent and antimycotic climbazole was detected for the first time in a WWTP effluent with concentrations up to 0.5 µg/L. Climbazole acts as a C14-demethylase inhibitor (DMI) fungicide and thus has a high efficacy against fungi, but knowledge of its potential environmental impact is lacking. Therefore, the aim of the present study was to characterize climbazole's ecotoxicity by conducting standard biotests with organisms representing different trophic levels from the aquatic as well as the terrestrial ecosystems. It was found that the toxicity of climbazole is mostly similar to that of other DMI fungicides, whereas it proved to be particularly toxic to primary producers. The lowest median effective concentrations (EC50s) were determined for Lemna minor, at 0.013 mg/L (biomass yield), and Avena sativa, at 18.5 mg/kg soil dry weight (shoot biomass). Reduction of frond size in water lentils and shoot length in higher plants suggested an additional plant growth-retarding mode of action of climbazole. In addition, it was demonstrated here that for an ionizable compound such as climbazole, the soil pH can have a considerable influence on phytotoxicity.

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Section: Introductionmentioning

confidence: 99%

Ecotoxicity of climbazole, a fungicide contained in antidandruff shampoo

Richter

Wick

Ternes

et al. 2013

Environmental Toxicology and Chemistry

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“…Though a battery of genotoxicity tests is used to evaluate the anti‐clastogenic effect of medicinal plants or their active constituents, the frequency of micro‐nucleated polychromatic erythrocytes (MnPCEs), chromosomal aberrations and single cell gel (comet) assay in bone marrow cells is commonly employed [9].…”

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confidence: 99%

Anti‐Clastogenic Effect of Berberine against DMBA‐Induced Clastogenesis

Sindhu

Manoharan

2010

Basic Clin Pharma Tox

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Our aim was to evaluate the protective effect of berberine on 7,12-dimethylbenz [a]anthracene (DMBA)-induced chromosomal aberrations and micro-nucleated polychromatic erythrocytes (MnPCEs) frequency in bone marrow cells of golden Syrian hamsters. The anti-clastogenic effect of berberine (50 mg ⁄ kg b.w. p.o.) was also assessed by measuring the status of phase II detoxification enzymes and oxidative stress, as biochemical endpoints, during DMBA (30 mg ⁄ kg b.w. i.p.) induced clastogenesis. Marked chromosomal aberrations, increased MnPCEs frequency and enhanced status of lipid peroxidation, antioxidants and phase I and II detoxification enzymes were noticed in hamsters treated with DMBA alone. Oral pretreatment with berberine for 5 days to DMBA-treated hamsters significantly reduced the frequency of MnPCEs and chromosomal abnormalities as well as reversed the status of lipid peroxidation, antioxidants and phase I and II detoxification enzymes. The present study thus suggests that berberine has potent anti-clastogenic potential against DMBA-induced clastogenesis, which is probably due to its anti-lipid peroxidative potential and effect on modulation of phase I and II detoxification cascade.Somatic cell mutation plays a crucial role in the initiation and promotion of carcinogenesis. Polycyclic aromatic hydrocarbons exert mutagenic and carcinogenic effects in biological systems if they are metabolically activated to more reactive forms [1]. 7,12-Dimethylbenz[a]anthracene (DMBA), a potent and best characterised organ-specific carcinogen, attacks DNA through its active metabolite 4-dihydrodiol-1,2-epoxide. DMBA firmly binds to epidermal DNA and generates a complex DNA adduct profile [2]. DMBA is therefore widely used to induce clastogenesis in experimental animals.The investigation of new anti-clastogenic and anti-carcinogenic compounds is essential in the modern human civilization due to rise in undesirable genetic mutations and increase in cancer risk [3]. In vivo models with laboratory animals are the reliable approaches to predict the clastogenic or anti-clastogenic potential of natural or synthetic agents [4]. Bone marrow cells were commonly employed as a tool for the evaluation of clastogenic and anti-clastogenic efficacy of carcinogens and anti-cancer compounds, respectively. An abnormality in chromosomal structure (translocation, deletion, duplication) and chromosomal number due to exposure to chemical carcinogen and ⁄ or mutagen is associated with increased risk of cancer and in the progression of neoplastic transformation [5]. Gaizev et al. and Hayashi et al. reported that measurement of micronuclei in polychromatic erythrocytes is suitable to identify a mutagenic substance due to the reason that their macronucleus is extruded in the processes of their formation from erythroblasts [6,7]. Also, it is easy to examine chromosomal aberrations in the metaphase stage due to its compact arrangement [8].Though a battery of genotoxicity tests is used to evaluate the anti-clastogenic effect of medicinal plant...

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“…() reported that ROS may play an essential role in DNA damage and apoptosis. Some other authors reported the genotoxicity of some antifungal drugs (Hassan, ; Yüzbaşioğlu et al., ) and of itraconazole (El‐Shershaby et al., ) , however, other authors reported the absence of genotoxicity of other antifungal drugs (Perez‐Rivera et al., ).…”

Section: Discussionmentioning

confidence: 99%