A case study on quantitative in vitro to in vivo extrapolation for environmental esters: Methyl-, propyl- and butylparaben

Campbell, Jerry L.; Yoon, Miyoung; Clewell, Harvey J.

doi:10.1016/j.tox.2015.03.010

Cited by 27 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The quantitative use of in vitro toxicity assays to determine safe exposure levels in humans requires extrapolation from the media concentrations that produce a significant effect to the in vivo exposures that would be expected to produce an effect (Campbell et al 2015 ). Before quantitative in vitro to vivo extrapolations (QIVIVE) are safely implemented, standardization methods that take into account uncertainties of the assessment of volatile/oxidizable compounds are needed.…”

Section: Discussionmentioning

confidence: 99%

The in vitro assessment of the toxicity of volatile, oxidisable, redox-cycling compounds: phenols as an example

et al. 2021

View full text Add to dashboard Cite

Phenols are regarded as highly toxic chemicals. Their effects are difficult to study in in vitro systems because of their ambiguous fate (degradation, auto-oxidation and volatility). In the course of in vitro studies of a series of redox-cycling phenols, we found evidences of cross-contamination in several in vitro high-throughput test systems, in particular by trimethylbenzene-1, 4-diol/trimethylhydroquinone (TMHQ) and 2,6-di-tertbutyl-4-ethylphenol (DTBEP), and investigated in detail the physicochemical basis for such phenomenon and how to prevent it. TMHQ has fast degradation kinetics followed by significant diffusion rates of the resulting quinone to adjacent wells, other degradation products being able to air-diffuse as well. DTBEP showed lower degradation kinetics, but a higher diffusion rate. In both cases the in vitro toxicity was underestimated because of a decrease in concentration, in addition to cross-contamination to neighbouring wells. We identified four degradation products for TMHQ and five for DTBEP indicating that the current effects measured on cells are not only attributable to the parent phenolic compound. To overcome these drawbacks, we investigated in detail the physicochemical changes occurring in the course of the incubation and made use of gas-permeable and non-permeable plastic seals to prevent it. Diffusion was greatly prevented by the use of both plastic seals, as revealed by GC–MS analysis. Gas non-permeable plastic seals, reduced to a minimum compounds diffusion as well oxidation and did not affect the biological performance of cultured cells. Hence, no toxicological cross-contamination was observed in neighbouring wells, thus allowing a more reliable in vitro assessment of phenol-induced toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

The in vitro assessment of the toxicity of volatile, oxidisable, redox-cycling compounds: phenols as an example

et al. 2021

View full text Add to dashboard Cite

show abstract

“…‐ a UF A of 3 was applied to account for toxicodynamic differences between in vitro cell‐based assays and humans according to Quantitative in vitro to in vivo extrapolation (QIVIVE) (Campbell et al, ). This value was adopted because a dosimetric adjustment from in vitro to in vivo has already been incorporated (DAF index) (US EPA, ).…”

Section: Methodsmentioning

confidence: 99%

New probabilistic risk assessment of ethylhexyl methoxycinnamate: Comparing the genotoxic effects of trans‐ and cis‐EHMC

Nečasová

Bányiová

Literák

et al. 2016

Environmental Toxicology

View full text Add to dashboard Cite

Ethylhexyl methoxycinnamate (EHMC) is a widely used UV filter present in a large number of personal care products (PCPs). Under normal conditions, EHMC occurs in a mixture of two isomers: trans-EHMC and cis-EHMC in a ratio of 99:1. When exposed to sunlight, the trans isomer is transformed to the less stable cis isomer and the efficiency of the UV filter is reduced. To date, the toxicological effects of the cis-EHMC isomer remain largely unknown. We developed a completely new method for preparing cis-EHMC. An EHMC technical mixture was irradiated using a UV lamp and 98% pure cis-EHMC was isolated from the irradiated solution using column chromatography. The genotoxic effects of the isolated cis-EHMC isomer and the nonirradiated trans-EHMC were subsequently measured using two bioassays (SOS chromotest and UmuC test). In the case of trans-EHMC, significant genotoxicity was observed using both bioassays at the highest concentrations (0.5 - 4 mg mL ). In the case of cis-EHMC, significant genotoxicity was only detected using the UmuC test at concentrations of 0.25 - 1 mg mL . Based on these results, the NOEC was calculated for both cis- and trans-EHMC, 0.038 and 0.064 mg mL , respectively. Risk assessment of dermal, oral and inhalation exposure to PCPs containing EHMC was carried out for a female population using probabilistic simulation and by using Quantitative in vitro to in vivo extrapolation (QIVIVE). The risk of cis-EHMC was found to be ∼1.7 times greater than trans-EHMC. In the case of cis-EHMC, a hazard index of 1 was exceeded in the 92nd percentile. Based on the observed differences between the isomers, EHMC application in PCPs requires detailed reassessment. Further exploration of the toxicological effects and properties of cis-EHMC is needed in order to correctly predict risks posed to humans and the environment. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 569-580, 2017.

show abstract

“…In one study, a physiologically based pharmacokinetic (PBPK) model was developed and used to estimate the plasma free paraben concentration in adults consistent with 95th percentile urine concentration reported in US National Health and Nutrition Examination Survey (NHANES) program (2009-2010 collection period). 59 For the 2009 to 2010 sampling period, the…”

Section: Physiologically Based Pharmacokinetic Modelingmentioning

confidence: 99%

Amended Safety Assessment of Parabens as Used in Cosmetics

Cherian¹,

Zhu²,

Bergfeld³

et al. 2020

Int J Toxicol

View full text Add to dashboard Cite

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 21 parabens as preservatives in cosmetic products. All of these ingredients are reported to function in cosmetics as preservatives; however, 5 are reported to also function as fragrance ingredients. The Panel reviewed relevant data relating to the safety of these ingredients under the reported conditions of use in cosmetic formulations. The Panel concluded that 20 of the 21 parabens included in this report are safe in cosmetics in the present practices of use and concentration described in this safety assessment when the sum of the total parabens in any given formulation does not exceed 0.8%. However, the available data are insufficient to support a conclusion of safety for benzylparaben in cosmetics.

show abstract

A case study on quantitative in vitro to in vivo extrapolation for environmental esters: Methyl-, propyl- and butylparaben

Cited by 27 publications

References 30 publications

The in vitro assessment of the toxicity of volatile, oxidisable, redox-cycling compounds: phenols as an example

The in vitro assessment of the toxicity of volatile, oxidisable, redox-cycling compounds: phenols as an example

New probabilistic risk assessment of ethylhexyl methoxycinnamate: Comparing the genotoxic effects of trans‐ and cis‐EHMC

Amended Safety Assessment of Parabens as Used in Cosmetics

Contact Info

Product

Resources

About