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

Won, Hansol; Jeong, Da Hye; Shin, Hye-Sun; Lee, Jin Hee; Lee, Jeong Pyo; Yang, Jun-Young; Jung, Kyoung Hwa; Jeong, Jayoung; Oh, Jun Ho

doi:10.3389/fphar.2021.690141

Cited by 5 publications

(6 citation statements)

References 24 publications

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“…In the in vivo dermal study, 2.34 mg/kg of BCP was applied to rat dorsal skin and 12.2 ± 2.63% of bioavailability was observed. However, in another in vivo dermal study [9], BCP absorption in the hydrogel formulation was 29.25 ± 6.09% following 0.262 mg/kg rat dorsal application. In accordance with Im et al, the application doses affected skin absorption.…”

Section: Discussionmentioning

confidence: 87%

“…Moreover, the results of in silico and in vitro studies have shown that BCP interferes with nuclear receptor function and acts as an antagonist of the androgen receptor, estrogen receptor α, glucocorticoid receptor, and thyroid receptors α and β [8]. In addition, in a study by Won et al on repeated-dose oral toxicity of BCP for 28 days, the relative weight of the kidneys in female rats increased at a dosage of 500 and 1000 mg/kg, and their hematological and histopathological characteristics were altered at these dosages [9]. They also reported in vivo dermal absorption in rats, but the analysis method used for the evaluation of BCP concentration and the formulation applied to the skin were unclear.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and the Dermal Absorption of Bromochlorophene, a Cosmetic Preservative Ingredient, in Rats

Lee

Kim²,

Pham³

et al. 2022

Toxics

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The cosmetic industry has flourished in recent years. Accordingly, the safety of cosmetic ingredients is increasing. Bromochlorophene (BCP) is a commonly used cosmetic preservative. To evaluate the effects of BCP exposure, in vitro dermal absorption and in vivo pharmacokinetic (PK) studies were conducted using gel and cream formulations. The Franz diffusion cell system and rat dorsal skin were used for tests according to the Korea Ministry of Food and Drug Safety guidelines for in vitro skin absorption methods. After the dermal application (1.13 mg/cm2) of BCP in the gel and cream formulations, liquid chromatography–mass spectrometry (LC–MS/MS) was used to evaluate the amount of BCP that remained unabsorbed on the skin (WASH), and that was present in the receptor fluid (RF), stratum corneum (SC), and (epi)dermis (SKIN). The total dermal absorption rate of BCP was 7.42 ± 0.74% for the gel formulation and 1.5 ± 0.9% for the cream formulation. Total recovery in an in vitro dermal absorption study was 109.12 ± 8.79% and 105.43 ± 11.07% for the gel and cream formulations, respectively. In vivo PK and dermal absorption studies of BCP were performed following the Organization for Economic Cooperation and Development guidelines 417 and 427, respectively. When intravenous (i.v.) pharmacokinetics was performed, BCP was dissolved in glycerol formal and injected into the tail vein (n = 3) of the rats at doses of 1 and 0.2 mg/kg. Dermal PK parameters were estimated by the application of the gel and cream formulations (2.34 mg/kg of BCP as an active ingredient) to the dorsal skin of the rats. Intravenous and dermal PK parameters were analyzed using a non-compartmental method. The dermal bioavailability of BCP was determined as 12.20 ± 2.63% and 4.65 ± 0.60% for the gel and cream formulations, respectively. The representative dermal absorption of BCP was evaluated to be 12.20 ± 2.63% based on the results of the in vivo PK study.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and the Dermal Absorption of Bromochlorophene, a Cosmetic Preservative Ingredient, in Rats

Lee

Kim²,

Pham³

et al. 2022

Toxics

View full text Add to dashboard Cite

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“…Monitoring urine output, proteins, and glucose levels can help determine renal toxicity (Patel et al, 2018). In humans and animals, exposure to various hazardous chemicals raises oxidant levels and induces oxidative DNA damage, which leads to cellular damage and tissue necrosis (Won et al, 2021). All organs showed normal histology and indicated no pathological damage.…”

Section: Discussionmentioning

confidence: 99%

Newly synthesized acridone derivatives targeting lung cancer: A toxicity and xenograft model study

Bhusare,

Yadav,

Nandave

et al. 2024

Drug Development Research

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AKT is one of the overexpressed targets in nonsmall cell lung cancer (NSCLC) and plays an important role in its progression and offers an attractive target for the therapy. The PI3K/AKT/mTOR pathway is upregulated in NSCLC. Acridone is an important heterocycle compound which treats cancer through various mechanisms including AKT as a target. In the present work, the study was designed to evaluate the safety profile of three acridone derivatives (AC‐2, AC‐7, and AC‐26) by acute and repeated dose oral toxicity. In addition to this, we also checked the pAKT overexpression and its control by these derivatives in tumor xenograft model. The results from acute and repeated dose toxicity showed these compounds to be highly safe and free from any toxicity, mortality, or significant alteration in body weight, food, and water intake in the rats. In the repeated dose toxicity, compounds showed negligible variations in a few hematological parameters at 400 mg/kg. The histopathology, biochemical, and urine parameters remained unchanged. The xenograft model study demonstrated AC‐2 to be inhibiting HOP‐62 induced tumor via reduction in p‐AKT1 (Ser473) expression significantly. In immunofluorescence staining AC‐2 treated tissue section showed 2.5 fold reduction in the expression of p‐AKT1 (Ser473). Histopathology studies showed the destruction of tumor cells with increased necrosis after treatment. The study concluded that AC‐2 causes cell necrosis in tumor cells via blocking the p‐AKT1 expression. The findings may provide a strong basis for further clinical applications of acridone derivatives in NSCLC.

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“…Only the micronucleus test result was unable to obtain accurate genotoxicity (mutagenicity) information; therefore, further genotoxicity test is required for confirmation of genotoxicity of CEAE. In addition to the micronucleus test, other in vitro assay systems have been also used to evaluate the genotoxic potential of tested substances including the Ames test, chromosomal aberration test, and Comet assay [ 27 – 29 ]. In this study, the in vitro chromosomal aberration test in CHL cells indicated that CEAE did not produce chromosomal damage-inducing potential ( Table 4 ), further underpinning the ascertainment of nongenotoxicity of CEAE.…”

Section: Discussionmentioning

confidence: 99%

Toxicological Evaluation of Camellia euphlebia Leaves Aqueous Extract Using Acute and Subacute Toxicity Studies in Mice and Genotoxicity Studies

2022

Evidence-Based Complementary and Alternative Medicine

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Camelliaeuphlebia is a novel food source and Chinese folk medicine with multiple pharmacological properties. Our previous exploration has demonstrated the antidepressant-like activity of Camellia euphlebia leaves aqueous extract by reliable animal models of depression; however, a lack of toxicological information limits its pharmacological application. The present study aimed to evaluate the preliminary safety of C. euphlebia extract by determining acute/subacute toxicity in mice and in vivo/in vitro genotoxicity. The oral-medium lethal dose of the extract in mice was found to be higher than 5000 mg/kg body weight in the acute toxicity study. In a 14-days subacute toxicity study, C. euphlebia extract at doses of 400, 800, and 1600 mg/kg did not result in significant changes in food intake, water intake, body weight, relative organ weight, aspartate aminotransferase activity, alanine aminotransferase activity, creatinine level, and number of white blood cells and red blood cells. However, histopathology observation of organs taken from all mice showed that 1600 mg/kg extract caused slight hydropic degeneration in the cytoplasm of hepatocytes. In a 28-days subacute toxicity study, 600 mg/kg extract significantly increased the level of red blood cells but produced no negative side effects on other pathological parameters. Mice treated with the extract at doses of 200, 400, and 600 mg/kg for 28 days did not manifest any histopathological alterations of the liver, kidney, and spleen. Additionally, the extract showed no chromosomal aberrations in the in vivo micronucleus test and in vitro chromosomal aberration test. The results revealed that the extract showed no significant toxic effects and no potential genotoxicity but with the likelihood of transient erythrocytosis and slight hepatotoxicity. Further chronic toxicological evaluation involved in more physiological parameters, especially associated with liver toxicity and erythropoietin level, would be needed to determine its safety and application value.

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

Cited by 5 publications

References 24 publications

Pharmacokinetics and the Dermal Absorption of Bromochlorophene, a Cosmetic Preservative Ingredient, in Rats

Pharmacokinetics and the Dermal Absorption of Bromochlorophene, a Cosmetic Preservative Ingredient, in Rats

Newly synthesized acridone derivatives targeting lung cancer: A toxicity and xenograft model study

Toxicological Evaluation of Camellia euphlebia Leaves Aqueous Extract Using Acute and Subacute Toxicity Studies in Mice and Genotoxicity Studies

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