Improving the reliability of aquatic toxicity testing of hydrophobic chemicals via equilibrium passive dosing – A multiple trophic level case study on bromochlorophene

Stibany, Felix; Ewald, Franziska; Miller, Ina; Hollert, Henner; Schäffer, Andreas

doi:10.1016/j.scitotenv.2017.01.082

Cited by 17 publications

(12 citation statements)

References 39 publications

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“…Bromochlorophene is a preservative that was used in various personal care products where there was dermal (e.g., deodorants, soaps) and oral (e.g., dental care products) human exposure ( Stibany et al. 2017 ), yet there is a lack of human exposure data and lack of data on environmental concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings and data from previous studies on triclosan are summarized in Table 3. Bromochlorophene is a preservative that was used in various personal care products where there was dermal (e.g., deodorants, soaps) and oral (e.g., dental care products) human exposure (Stibany et al 2017), yet there is a lack of human exposure data and lack of data on environmental concentrations. Bromochlorophene has been rarely evaluated, and to the best of our knowledge, there have not been any studies that have looked into its effects on nuclear receptors to date.…”

Section: --mentioning

confidence: 99%

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Triclocarban, Triclosan, Bromochlorophene, Chlorophene, and Climbazole Effects on Nuclear Receptors: An in Silico and in Vitro Study

Kenda

Kuželički

Iida³

et al. 2020

Environ Health Perspect

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BACKGROUND: Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly difficult due to lack of adequate toxicological tests. This difficulty is particularly problematic for cosmetic ingredients, because in vivo testing is now banned completely in the European Union. OBJECTIVES: The aim was to identify candidate preservatives as endocrine disruptors by in silico methods and to confirm endocrine receptors' activities through nuclear receptors in vitro. METHODS: We screened preservatives listed in Annex V in the European Union Regulation on cosmetic products to predict their binding to nuclear receptors using the Endocrine Disruptome and VirtualToxLab™ version 5.8 in silico tools. Five candidate preservatives were further evaluated for androgen receptor (AR), estrogen receptor (ERa), glucocorticoid receptor (GR), and thyroid receptor (TR) agonist and antagonist activities in cellbased luciferase reporter assays in vitro in AR-EcoScreen, hERa-HeLa-9903, MDA-kb2, and GH3.TRE-Luc cell lines. Additionally, assays to test for false positives were used (nonspecific luciferase gene induction and luciferase inhibition). RESULTS: Triclocarban had agonist activity on AR and ERa at 1 lM and antagonist activity on GR at 5 lM and TR at 1 lM. Triclosan showed antagonist effects on AR, ERa, GR at 10 lM and TR at 5 lM, and bromochlorophene at 1 lM (AR and TR) and at 10 lM (ERa and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC 50) IC 50 = 2:4 lM], as for its substantial ERa agonist at >5 lM and TR antagonist activity at 10 lM. Climbazole showed AR antagonist (IC 50 = 13:6 lM), ERa agonist at >10 lM, and TR antagonist activity at 10 lM. DISCUSSION: These data support the concerns of regulatory authorities about the endocrine-disrupting potential of preservatives. These data also define the need to further determine their effects on the endocrine system and the need to reassess the risks they pose to human health and the environment.

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Section: Discussionmentioning

confidence: 99%

Section: --mentioning

confidence: 99%

Triclocarban, Triclosan, Bromochlorophene, Chlorophene, and Climbazole Effects on Nuclear Receptors: An in Silico and in Vitro Study

Kenda

Kuželički

Iida³

et al. 2020

Environ Health Perspect

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“…associated with the hydrophobicity/solubility of the chemical; ii) perform, in similar conditions as the toxicity assay, an analytical determination of the concentrations, at least for the stock solutions and whenever possible for all dilutions made in the test medium. In the case of highly hydrophobic chemicals (log K OW > 5), specific methods like passive dosing should be considered (Brown et al, 2001;Vicquelin et al, 2011;Stibany et al, 2017bStibany et al, , 2017a to avoid a distorted EC estimation.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Demonstrating the need for chemical exposure characterisation in a microplate test system: toxicity screening of sixteen pesticides on two marine microalgae

et al. 2019

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Pesticides used in viticulture create a potential risk for the aquatic environment due to drift during application, runoff and soil leaching. The toxicity of sixteen pesticides and one metabolite were evaluated on the growth of two marine microalgae, Tisochrysis lutea and Skeletonema marinoi, in 96-h exposure assays conducted in microplates. For each substance, concentrations of stock solutions were analytically measured and abiotic assays were performed to evaluate the chemical stability of pesticides in microplates. For two chemicals, microalgae exposures were run simultaneously in microplates and culture flasks to compare EC 50 calculated from the two exposure systems. Results from chemical analyses demonstrated the low stability of hydrophobic pesticides (log K OW > 3). For such chemicals, EC 50 values calculated using measured pesticide concentrations were twofold lower than those first estimated using nominal concentrations. Photosystem II inhibitors were the most toxic herbicides, with EC 50 values below 10 μg L −1 for diuron and around double this for isoproturon. Chlorpyrifos-methyl was the only insecticide to significantly affect the growth of T. lutea, with an EC 50 around 400 μg L −1. All fungicides tested were significantly toxic to both species: strobilurins showed low overall toxicity, with EC 50 values around 400 μg L −1 , whereas quinoxyfen, and spiroxamine, showed high toxicity to both species, especially to T. lutea, with an EC 50 below 1 μg L −1 measured for spiroxamine in culture flasks. This study highlights the need to perform chemical analyses for reliable toxicity assessment and discusses the advantages and disadvantages of using microplates as a toxicity screening tool. 2 Please note that this is an author-produced PDF of an article accepted for publication following peer review. The definitive publisher-authenticated version is available on the publisher Web site. Highlights ► The toxicity of 17 pesticides was tested on two microalgae species. ► A microplate assay was developed for accurate determination of EC 50 values. ► Analytical measurement of exposure concentrations was performed. ► Significant differences between nominal and measured concentrations were found. ► Four herbicides, one insecticide and four fungicides showed significant toxicity.

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“…2-bromo-6-[(3-bromo-5-chloro-2-hydroxyphenyl) methyl]-4-chlorophenol (BCP), a hydrophobic chemical, is used as an anti-microbial agent in household chemicals like cosmetic emulsion, toothpaste, and deodorants (Moran et al, 2005;Stibany et al, 2017) BCP is a registered preservative at concentrations of up to 0.1% in cosmetic products in many countries, including Korea [MFDS (The Ministry of Food and Drug Safety), 2017a]. The various physicochemical characteristics of preservatives are the major determinants of their toxic potential Won et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Toxicological Assessment of Bromochlorophene: Single and Repeated-Dose 28-Day Oral Toxicity, Genotoxicity, and Dermal Application in Sprague–Dawley Rats

et al. 2021

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Bromochlorophene (BCP) has shown good properties in sterilization and antibacterial activity and is widely used as a household chemical. We evaluated the genotoxicity, single and repeated-dose 28-day oral toxicity, and dermal application of a BCP suspension in Sprague–Dawley (SD) rats. For the single-dose toxicity study, a dose of 25–1,000 mg per kg of bodyweight (mg/kg b.w.) of BCP was given once orally to SD rats. Mortality and clinical signs were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. For the repeated-dose 28-day toxicity study, the high dose was set at 1,000 mg/kg b.w. and the middle, middle-low, and low dose were set to 500, 250, and 125 mg/kg, respectively. Hematology and biochemistry parameters were examined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. A bacterial reverse mutation assay, in vitro chromosomal aberration assay, and in vivo micronucleus assay were performed to assess genotoxicity-dermal application exposure assessment of BCP in rats. A high oral approximate lethal dose (ALD) of 1,000 mg/kg was observed in the single-dose toxicity test. During the repeated-dose 28-day time period, most animal deaths after administration occurred during the first 3 weeks. The 1,000 mg/kg b.w. oral dose caused the death of six male rats (6/7) and four female rats (4/7). At 500 mg/kg b.w., the female rats showed mortality (1/7). For the biochemistry assays, cholesterol was increased significantly compared to vehicle in both sexes in the 250 and 500 mg/kg groups. Histopathological changes with treatment-related findings were observed in the pancreas in female rats treated with a high dose of BCP compared with the vehicle group. BCP showed no genotoxic effect. These data suggested that the ALD of BCP, estimated as a non-genotoxic substance, was over 1,000 mg/kg b.w. in the single-dose toxicity study, and the NOAEL of BCP was considered to be 250 mg/kg b.w. for male and female rats after repeated oral administration for 28 days under the present study conditions.

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Improving the reliability of aquatic toxicity testing of hydrophobic chemicals via equilibrium passive dosing – A multiple trophic level case study on bromochlorophene

Cited by 17 publications

References 39 publications

Triclocarban, Triclosan, Bromochlorophene, Chlorophene, and Climbazole Effects on Nuclear Receptors: An in Silico and in Vitro Study

Triclocarban, Triclosan, Bromochlorophene, Chlorophene, and Climbazole Effects on Nuclear Receptors: An in Silico and in Vitro Study

Demonstrating the need for chemical exposure characterisation in a microplate test system: toxicity screening of sixteen pesticides on two marine microalgae

Toxicological Assessment of Bromochlorophene: Single and Repeated-Dose 28-Day Oral Toxicity, Genotoxicity, and Dermal Application in Sprague–Dawley Rats

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