Does EU legislation allow the use of the Benchmark dose (BMD) approach for risk assessment?

Brandon, Esther; Bulder, Astrid S.; Engelen, J.G.M. van; Mahieu, C.M.; Mennes, Wim; Pronk, Marja E.J.; Rietveld, Anton; Ven, B.M. van de; Voorde, S.E.C.G. ten; Wolterink, Gerrit; Slob, Wout; Zeilmaker, Marco J.; Bessems, Jos

doi:10.1016/j.yrtph.2013.07.005

Cited by 11 publications

(9 citation statements)

References 8 publications

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“…Here, the benchmark dose (BMD) approach was used (EFSA, 2009 ) to derive a point of departure for further risk assessment, i.e. to obtain a health-based guidance value (Brandon et al, 2013 ; EFSA, 2009 , Filipsson et al, 2003 ). The advantage of this approach is that it provides a confidence interval around the BMD thus indicating the reliability of the data.…”

Section: Introductionmentioning

confidence: 99%

Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

et al. 2016

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Introduction: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment. Methods: Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C × T protocol). The dose is expressed as 6 h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2 mg/m3 CuO NPs, with a primary particle size of 10 9.2–14 nm and an MMAD of 1.5 μm. Results: Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4 mg/m3. After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2 mg/m3. The olfactory epithelium in the nose degenerated 24 h after exposure to 6.3 and 13.2 mg/m3, but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver. Conclusion: A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period.

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Section: Introductionmentioning

confidence: 99%

Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

et al. 2016

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“…To answer this question, all legal frameworks that require toxicological data for evaluation (and admission) of chemical substances were analyzed for possibilities and barriers for the use of alternatives (table 1). This study is comparable to a previous analysis for legal barriers that hamper the use of the benchmark dose (BMD) approach (Brandon et al, 2013). The BMD approach can lead to a refinement and reduction of animal use and ten legal frameworks were analyzed for legal barriers to use this approach.…”

Section: Methodsmentioning

confidence: 70%

Do current EU regulations for the safety assessment of chemical substances pose legal barriers for the use of alternatives to animal testing?

Heringa¹,

Wit²,

Bos³

et al. 2015

Toxicology Letters

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“…For the risk assessment of a particular chemical, different methods may predict different NOAEL values at different endpoints ( 2 ). The NOAEL and its related exposure level, the “lowest observed adverse effect level” (LOAEL), are usually selected from an actual experimental dose levels and are therefore affected considerably by the experimental design, such as dose range, and each dose selected ( 3 ). The benchmark procedure can be applied to various types of data, such as “dichotomous” and “continuous” data, to determine the dose that causes a prescribed adverse response.…”

Section: Introductionmentioning

confidence: 99%

Benchmark Dose Modeling of In Vitro Genotoxicity Data: a Reanalysis

Guo

Mei

2018

ToxicolRes

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The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4-position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machine-generated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA’s BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a two-fold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA’s BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.

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Does EU legislation allow the use of the Benchmark dose (BMD) approach for risk assessment?

Cited by 11 publications

References 8 publications

Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

Do current EU regulations for the safety assessment of chemical substances pose legal barriers for the use of alternatives to animal testing?

Benchmark Dose Modeling of In Vitro Genotoxicity Data: a Reanalysis

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