Studies of the effect of 2-(2′-hydroxy-5′-methylphenyl)benzotriazole on rat liver

Schmid, Karl; Schweizer, W; Stäubli, W.; Waechter, F.

doi:10.1016/0015-6264(80)90102-9

Cited by 8 publications

(9 citation statements)

References 21 publications

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“…Homogenates of two or three livers were then combined for preparation of the various liver subcellular fractions. Preparation of a ribosome-free microsomal fraction A washed microsomal fraction was prepared as previously described (Schmid et al, 1980). The ribosomes were removed by treatment of the microsomal fraction with pyrophosphate, followed by chromatography on Bio-Gel A-150m (50-100 mesh; Bio-Rad Laboratories, Richmond, CA, U.S.A.) (Remacle et al, 1976).…”

Section: A Nimalsmentioning

confidence: 99%

Immuno-electron-microscopic studies on the subcellular distribution of rat liver epoxide hydrolase and the effect of phenobarbitone and 2-acetamidofluorene treatment

Waechter¹,

Bentley²,

Germann³

et al. 1982

Biochemical Journal

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The distribution of rat liver epoxide hydrolase in various subcellular fractions was investigated by immuno-electron-microscopy. Ferritin-linked monospecific anti-(epoxide hydrolase) immunoglobulins bound specifically to the cytoplasmic surfaces of total microsomal preparations and smooth and rough microsomal fractions as well as the nuclear envelope. Specific binding was not observed when the ferritin conjugates were incubated with peroxisomes, lysosomes and mitochondria. The average specific ferritin load of the individual subcellular fractions correlated well with the measured epoxide hydrolase activities. This correlation was observed with fractions prepared from control, phenobarbitone-treated and 2-acetamidofluorene-treated rats.

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Section: A Nimalsmentioning

confidence: 99%

Immuno-electron-microscopic studies on the subcellular distribution of rat liver epoxide hydrolase and the effect of phenobarbitone and 2-acetamidofluorene treatment

Waechter¹,

Bentley²,

Germann³

et al. 1982

Biochemical Journal

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“…Hepatic glucose 6-phosphatase activity was decreased in the 14 days group. These results suggest that drometrizole is an enzyme inducer for the formation of mixed function oxidases with a slight stimulatory effect (28).…”

Section: Hazard Identificationmentioning

confidence: 94%

“…The radioactivity in urine and feces were about 73% and 27%, respectively. The residual radioactivity measured in the tissues was negligible and was lower than blood levels of 0.017 mg/g, except for the kidney, the aorta, and the liver (0.10 to 0.22 mg/g) (28).…”

Section: Toxicokineticsmentioning

confidence: 96%

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Risk Assessment of Drometrizole, a Cosmetic Ingredient used as an Ultraviolet Light Absorber

et al. 2019

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As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2′-hydroxy-5′-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

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“…Each animal was sacrificed by decapitation; the liver was removed and immediately placed on ice. Fractions of washed microsomes were prepared as described by Schmid et al (1980). The content of cytochrome P-450 in these fractions was evaluated by the method of Omura and Sato (1964).…”

Section: Hepatic Concentrations Of Mierosomal Cytochrome P-450 Andmentioning

confidence: 99%

Functional supersensitivity to adrenergic agonists in the rat after DSP-4, a selective noradrenergic neurotoxin

et al. 1983

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Rats treated with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenergic neurotoxin, showed no differences compared to control rats in the number of head dips, a measure of exploratory behavior. Since a previous neurochemical investigation had demonstrated that DSP-4 rats have supersensitive alpha 2- and beta-adrenergic receptors in certain regions of the central nervous system, the behavior of these animals was also examined after the injection of clonidine, an alpha 2 agonist, and clenbuterol, a beta agonist. These drugs reduced, in a dose-dependent manner, the head-dipping of both control and DSP-4 rats. However, this effect was of greater magnitude in DSP-4 animals. Control experiments suggested that the response to clonidine and clenbuterol was mediated centrally by alpha 2 and beta receptors, respectively. Other behavioral experiments with agonists of the dopaminergic and serotoninergic systems indicated that these neurotransmitter systems were unchanged in DSP-4 animals. The results are discussed in terms of the selective action of DSP-4 and the responsiveness of DSP-4 rats to adrenergic agonists. The DSP-4-treated rat may constitute a new model of functional supersensitivity to adrenergic agonists.

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Studies of the effect of 2-(2′-hydroxy-5′-methylphenyl)benzotriazole on rat liver

Cited by 8 publications

References 21 publications

Immuno-electron-microscopic studies on the subcellular distribution of rat liver epoxide hydrolase and the effect of phenobarbitone and 2-acetamidofluorene treatment

Immuno-electron-microscopic studies on the subcellular distribution of rat liver epoxide hydrolase and the effect of phenobarbitone and 2-acetamidofluorene treatment

Risk Assessment of Drometrizole, a Cosmetic Ingredient used as an Ultraviolet Light Absorber

Functional supersensitivity to adrenergic agonists in the rat after DSP-4, a selective noradrenergic neurotoxin

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