Toxicity of Antioxidants to <i>Tetrahymena pyriformis</i>*

Epstein, Samuel S.; Saporoschetz, Inna B.; Hutner, S. H.

doi:10.1111/j.1550-7408.1967.tb01991.x

Cited by 26 publications

(5 citation statements)

References 26 publications

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“…The oral lethal dose (LD 50 ) of drometrizole in mice was reported to be 6.5 g/kg and > 5.0 g/kg by Labor Hygiene and Occupational Diseases (20) and Epstein et al . (21), respectively (20,21). Oral toxicity was evaluated in rats for nail care cosmetics containing 1%, 0.3% and 0.03% of drometrizole.…”

Section: Hazard Identificationmentioning

confidence: 99%

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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Section: Hazard Identificationmentioning

confidence: 99%

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

et al. 2019

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“…Its use is subject to the limitations set forth in the Code of Federal Regulations (2003), Title 21, part 178.2010. Epstein et al (1965Epstein et al ( , 1967 reported that Drometrizole had very low cytotoxicity to Tetrahymena pyriformis, with a median LD 50 of 640 μg/ml.…”

Section: Noncosmeticmentioning

confidence: 99%

“…The acute oral LD 50 of Drometrizole in mice is given as 6.5 g/kg according to the Labor Hygiene and Occupational Diseases (1966), in the then Soviet Union, and >5.0 g/kg according to Epstein (1967). Komarova and Maksimova (1979) administered 5.0 and 10.0 g/kg Drometrizole, in sunflower oil, by stomach tube to white mice and rats.…”

Section: Acute Oral Toxicitymentioning

confidence: 99%

Amended Final Report of the Safety Assessment of Drometrizole as used in Cosmetics1

2008

Int J Toxicol

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Drometrizole is used in cosmetics as an ultraviolet (UV) light absorber and stabilizer. In an earlier safety assessment, the available data were found insufficient to support the safety of this ingredient, but new data have been provided and assessed. In voluntary industry reports to the Food and Drug Administration, this ingredient is reported to be used in noncoloring hair care products, and in an industry use concentration survey, uses in nail care products at 0.07% were reported. Drometrizole has absorbance maxima at 243, 298, and 340 nm. Drometrizole is used widely as a UV absorber and stabilizer in plastics, polyesters, celluloses, acrylates, dyes, rubber, synthetic and natural fibers, waxes, detergent solutions, and orthodontic adhesives. It is similarly used in agricultural products and insecticides. Drometrizole is approved as an indirect food additive for use as an antioxidant and/or stabilizer in polymers. Short-term studies using rats reported liver weight increases, increases in the activities of enzymes aminopyrine N-demethylase, and UDP glucuronosyl transferase, but no significant effects were noted in the activities of acid hydrolases or in hepatocyte organelles. Although Drometrizole is insoluble in water and soluble in a wide range of organic solvents, a distribution and elimination study using rats indicated that some Drometrizole was absorbed, then metabolized and excreted in the urine. Drometrizole and products containing Drometrizole were nontoxic in acute oral, inhalation, and dermal studies using animals. No increase in mortality or local and/or systemic toxicity were observed in a 13-week oral toxicity study using dogs; the no observed effect level (NOEL) was 31.75 mg/kg day(- 1) for males and 34.6 mg/kg day(-1) for females. In a 2-year feeding study using rats, a NOEL of 47 to 58 mg/kg day(- 1) was reported. Developmental studies of Drometrizole in rats and mice found no teratogenic effects and a NOEL of 1000 mg/kg day(- 1) was reported. Drometrizole was not genotoxic in Ames tests, a mouse bone marrow micronucleus test, or somatic mutation assays observing interphase nuclei and chromosomal aberrations using Chinese hamsters. There was no evidence of dominant lethal effects in studies using mice or rats. Drometrizole at a 1% concentration was minimally to moderately irritating to rabbit eyes, if followed by rinsing, but mildly to severely irritating in unrinsed eyes. A nail product containing 0.03% Drometrizole, however, was nonirritating to unrinsed rabbit eyes. A nail polish containing 1.0% Drometrizole was nonirritating to rabbit skin and Drometrizole was negative for sensitization in two Magnusson-Kligman maximization tests in guinea pigs. In clinical tests, Drometrizole at 1% was nonirritating in a single-insult patch test. No irritation or eczematous reactions were observed in 300 patients (with or without dermatosis) treated with daily applications of Drometrizole for 8 weeks. In a 3-year clinical therapeutic trial conducted to evaluate the effectiveness of two UV absorbing prepar...

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“…The majority of the studies on the toxicity of PNA used mammalian models, and the few data that exist on aquatic vertebrates were acute exposures. The EC 50 for cell proliferation was determined to be 2 mg/L for Tetrahymena pyriformis (ciliate) exposed to PNA for 48 h (Epstein et al 1967). The LC 50 was in the range of 0.44-0.74 mg/L for Oncorhynchus mykiss (rainbow trout) and 0.57-0.82 mg/L for Lepomis macrochirus (bluegill).…”

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confidence: 99%

N-phenyl-1-naphthylamine (PNA) Accumulates in Snapping Turtle (Chelydra serpentina) Liver Activating the Detoxification Pathway

Colson

Solla

Balakrishnan

et al. 2020

Bull Environ Contam Toxicol

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Substituted phenylamine antioxidants (SPAs) are used in Canadian industrial processes. SPAs, specifically N-phenyl-1-naphthylamine (PNA), have received very little attention despite their current use in Canada and their expected aquatic and environmental releases. There is a research gap regarding the effects of PNA in wildlife; therefore, Chelydra serpentina (common snapping turtle) was studied due to its importance as an environmental indicator species. A chronic experiment was performed using PNA spiked food (0 to 3446 ng/g) to determine its toxicity to juvenile C. serpentina. A significant increase in cyp1a mRNA level was observed in the liver of turtles exposed to 3446 ng/g PNA, suggesting that phase I detoxification is activated in the exposed animals. Additionally, a significant decrease in cyp2b transcript level was observed at the two lowest PNA doses, likely indicating another metabolic alteration for PNA. This study helped determine the molecular effects associated with a PNA exposure in reptiles.

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Toxicity of Antioxidants to *Tetrahymena pyriformis**

Cited by 26 publications

References 26 publications

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

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

Amended Final Report of the Safety Assessment of Drometrizole as used in Cosmetics1

N-phenyl-1-naphthylamine (PNA) Accumulates in Snapping Turtle (Chelydra serpentina) Liver Activating the Detoxification Pathway

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Toxicity of Antioxidants to Tetrahymena pyriformis*

Cited by 26 publications

References 26 publications

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

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

Amended Final Report of the Safety Assessment of Drometrizole as used in Cosmetics1

N-phenyl-1-naphthylamine (PNA) Accumulates in Snapping Turtle (Chelydra serpentina) Liver Activating the Detoxification Pathway

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Toxicity of Antioxidants to *Tetrahymena pyriformis**