The fate of dichlorophen in the rat

Dixon, Patrick A. F.; Caldwell, John

doi:10.1007/bf03189376

Cited by 8 publications

(4 citation statements)

References 8 publications

(4 reference statements)

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“…Both bithionol and dichlorophen share structures with two free phenolic hydroxyl groups, allowing them to be readily conjugated and absorbed in the gastrointestinal tract, as shown in dichlorophen administration to rats. 40 While the pharmacokinetics of dichlorophen has not been fully determined, in the context of repurposing, dichlorophen's clinical use as an oral anticestodal, antifungal, and antimicrobial treatment suggests its potential as a treatment for inhalatory, gastrointestinal, or injection anthrax infection. 41 Suloctidil's extremely high synergistic efficacy of almost 100% B. cereus growth inhibition independently and in all combinations with other hits at its sub-MIC in liquid assays suggests a possibility for inhibitory efficacy at further dilutions in combination therapies (Figure 5).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…anthracis treatment. Both bithionol and dichlorophen share structures with two free phenolic hydroxyl groups, allowing them to be readily conjugated and absorbed in the gastrointestinal tract, as shown in dichlorophen administration to rats . While the pharmacokinetics of dichlorophen has not been fully determined, in the context of repurposing, dichlorophen’s clinical use as an oral anticestodal, antifungal, and antimicrobial treatment suggests its potential as a treatment for inhalatory, gastrointestinal, or injection anthrax infection …”

Section: Resultsmentioning

confidence: 99%

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Repurposing Clinically Approved Drugs for the Treatment of Bacillus cereus, a Surrogate for Bacillus anthracis

et al. 2020

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Of the numerous infectious diseases afflicting humans, anthrax disease, caused by Bacillus anthracis , poses a major threat in its virulence and lack of effective treatment. The currently lacking standards of care, as well as the lengthy drug approval process, demonstrate the pressing demand for treatment for B. anthracis infections. The present study screened 1586 clinically approved drugs in an attempt to identify repurposable compounds against B. cereus , a relative strain that shares many physical and genetic characteristics with B. anthracis . Our study yielded five drugs that successfully inhibited B. cereus growth: dichlorophen, oxiconazole, suloctidil, bithionol, and hexestrol. These drugs exhibited varying levels of efficacy in broad-spectrum experiments against several Gram-positive and Gram-negative bacterial strains, with hexestrol showing the greatest inhibition across all tested strains. Through tests for the efficacy of each drug on B. cereus , bithionol was the single most potent compound on both solid and liquid media and exhibited even greater eradication of B. cereus in combination with suloctidil on solid agar. This multifaceted in vitro study of approved drugs demonstrates the potential to repurpose these drugs as treatments for anthrax disease in a time-efficient manner to address a global health need.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Repurposing Clinically Approved Drugs for the Treatment of Bacillus cereus, a Surrogate for Bacillus anthracis

et al. 2020

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“…This assumption has to be verified by more thorough analysis, when greater amounts have been isolated and purified. Diconjugates of small drug molecules are comparatively rare, but have been reported by Vestermark & Bostrom (1960), Millburn et al (1967 , Parke (1968), Dixon & Caldwell (1978) and Hawkins (1981).…”

Section: Discussionmentioning

confidence: 99%

Studies on Laxatives: Biliary and Urinary Excretion in Rats Given Danthron by Intravenous Infusion or Gastric Intubation

Sund¹

1987

Pharmacology & Toxicology

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Rats were infused with danthron (I) at doses of 0.48, 2.2 and 5.8 mumol/100 g body weight, or given 12 mumol/100 g with gastric tube. TLC of bile and urine demonstrated a number of metabolites, at both administration routes. These included I monosulphate (II) and -glucuronide (III), two other phase 2 metabolites which behaved as the corresponding diconjugates, and several phase 1 metabolites (IV) in conjugated form. IV as a group were estimated by photometry of hydrolysed samples, using I as a reference. Danthron conjugates as a group were determined in such samples by a specific method for I. Moreover, II and III were determined individually in unhydrolysed specimens. Following infusion, about 80% of the danthron conjugates in bile were excreted after 1 hour; the dose fractions found after 5 hours represented about 20%, 30%, and 40% at the low, intermediate and high dose level, respectively. The corresponding fractions in urine were 16%, 12% and 10%, giving rise to bile:urine excretion ratios of 1.3, 2.7 and 4.0, respectively. This change in excretion pattern was associated with changes in metabolite muster, which involved a decrease in the balance of IV:I conjugates, as well as an increase in III:II ratio. IV was more abundantly present in bile than in urine, and showed a more sustained excretion than the I conjugates. By intragastric administration, the cumulated excretion (bile + urine) of I conjugates were only 6%, 8% and 5% of dose, in three consecutive 6 hours' periods (0-6, 6-12 and 12-18 hours after dosing). The bile:urine excretion ratios seemed to decrease with time, as did the III:II ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Absorption, Distribution, Metabolism, Excretion Dichlorophene Dixon and Caldwell (1978) dosed female Wistar albino rats (3/group) orally with 50 mg/kg [ 14 C] Dichlorophene dissolved in propane-1,2-diol. One group of rats was bile-duct cannulated 1 h after oral administration of [ 14 C]Dichlorophene.…”

Section: General Biologymentioning

confidence: 99%

Safety Assessment of Dichlorophene and Chlorophene1

Yamarik¹

2004

Int J Toxicol

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Dichlorophene is a halogenated phenolic compound that functions as a bacteriocide and fungicide in cosmetics. Chlorophene is a halogenated phenolic compound that functions as a biocide and preservative in cosmetics. Dichlorophene was reported to be used in a total of five cosmetic formulations at concentrations of 0% to 1.0%, but Chlorophene was not reported to be used. Dichlorophene is prohibited for use in cosmetic ingredients in Japan. In Europe, the maximum authorized concentration allowed for Dichlorophene is 0.5% and for Chlorophene is 0.2%. The major impurity of Dichlorophene is the trimer 4-chloro-2,6-bis(5-chloro-2-hydroxy-benzyl)phenol. In rats, Dichlorophene sulfate, Dichlorophene monoglucuronide, and Dichlorophene diglucuronide were the major metabolites of Dichlorophene and were excreted, mainly in the urine. The glucuronic acid conjugate, the sulfate ester conjugate, and two minor metabolites of Chlorophene were the metabolites found in rat urine. Chlorophene was incompletely absorbed through the rat skin. These chemicals exhibited low toxicity in acute oral toxicity studies in several animal species. Some evidence of toxicity with both chemicals was found in short-term oral toxicity studies in mice and rats; nephropathy was the principal finding. Chronic toxicity data were not available for Dichlorophene. Rats and mice dosed with Chlorophene for 2 years had a dose-related and sex-related increase in the severity of nephropathy. In animal tests, Dichlorophene and Chlorophene were ocular irritants. No inhalation toxicity data were available for these ingredients. Dichlorophene up to 10% concentration resulted in no to minimal irritation when applied to the intact and abraded skin of rabbits. Chlorophene was severely irritating to rabbits in most dermal irritation studies. Studies on guinea pigs gave positive and negative results in sensitization tests of Dichlorophene. A dose-related contact hypersensitivity response to Chlorophene was reported in mice. No reproductive or developmental toxicity data were available for Dichlorophene, but there was some evidence of non-dose-dependent developmental toxicity with Chlorophene in rabbits. Dichlorophene was positive in the Ames mutagenicity assay, but not in mammalian or fruit fly test systems. Chlorophene was mutagenic in four in vitro mammalian test systems. Carcinogenicity studies for Dichlorophene were not found. Neoplasms were not observed in rats treated with Chlorophene for 2 years; however a significant incidence of neoplasms was observed in mice so treated. A 1-year National Toxicology Program (NTP) study concluded that Chlorophene was a cutaneous irritant and a weak skin tumor promoter but had no activity as an initiator or complete carcinogen. Dichlorophene was not a sensitizer in clinical dermal sensitization tests. Some reactions to Chlorophene occurred in some, but not all, clinical dermal sensitization tests. Positive photopatch tests to Dichlorophene were found in 13/469 patients. Although these ingredients were ocular irritants at high concentrations, the risk at concentrations which are actually used in cosmetic formulations was uncertain. Overall, the available data were insufficient to support safety of Dichlorophene or Chlorophene. Additional data needed include (1) method of manufacture and impurities data (especially the trimer in Dichlorophene); (2) photosensitization and photo-carcinogenicity data for Dichlorophene; (3) dermal reproductive and developmental toxicity data for Dichlorophene (as a function of dose); and (4) ocular irritation at concentration of use, if available.

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The fate of dichlorophen in the rat

Cited by 8 publications

References 8 publications

Repurposing Clinically Approved Drugs for the Treatment of Bacillus cereus, a Surrogate for Bacillus anthracis

Repurposing Clinically Approved Drugs for the Treatment of Bacillus cereus, a Surrogate for Bacillus anthracis

Studies on Laxatives: Biliary and Urinary Excretion in Rats Given Danthron by Intravenous Infusion or Gastric Intubation

Safety Assessment of Dichlorophene and Chlorophene1

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