Oral-to-inhalation route extrapolation in occupational health risk assessment: a critical assessment

Rennen, Monique; Bouwman, Tialda; Wilschut, Annette; Bessems, Jos; Heer, Cees de

doi:10.1016/j.yrtph.2003.09.003

Cited by 32 publications

(19 citation statements)

References 11 publications

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“…Inhalation of insoluble inorganic (nano)particles or MWCNTs will (most probably) not lead to systemic absorption and distribution but rather induce local effects in the lung, which potentially may lead to systemic effects (e.g. cardiovascular diseases), but are different from those induced following oral absorption (Rennen et al, 2004, Saber et al, 2014). …”

Section: Resultsmentioning

confidence: 99%

Chemical alternatives assessment of different flame retardants – A case study including multi-walled carbon nanotubes as synergist

Aschberger

Campia

Pesudo

et al. 2017

Environment International

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Flame retardants (FRs) are a diverse group of chemicals used as additives in a wide range of products to inhibit, suppress, or delay ignition and to prevent the spread of fire. Halogenated FRs (HFRs) are widely used because of their low impact on other material properties and the low loading levels necessary to meet the required flame retardancy. Health and environmental hazards associated with some halogenated FRs have driven research for identifying safer alternatives. A variety of halogen-free FRs are available on the market, including organic (phosphorus and nitrogen based chemicals) and inorganic (metals) materials. Multi-walled carbon nanotubes (MWCNT) have been demonstrated to act as an effective/synergistic co-additive in some FR applications and could thereby contribute to reducing the loading of FRs in products and improving their performance.As part of the FP7 project DEROCA we carried out a chemical alternatives assessment (CAA). This is a methodology for identifying, comparing and selecting safer alternatives to chemicals of concern based on criteria for categorising human and environmental toxicity as well as environmental fate. In the project we assessed the hazard data of different halogen-free FRs to be applied in 5 industrial and consumer products and here we present the results for MWCNT, aluminium diethylphosphinate, aluminium trihydroxide, N-alkoxy hindered amines and red phosphorus compared to the HFR decabromodiphenylether. We consulted the REACH guidance, the criteria of the U.S.-EPA Design for Environment (DfE) and the GreenScreen® Assessment to assess and compare intrinsic properties affecting the hazard potential.A comparison/ranking of exposure reference values such as Derived No Effect Levels (DNELs) showed that FRs of concern are not identified by a low DNEL. A comparison based on hazard designations according to the U.S.-EPA DfE and GreenScreen® for human health endpoints, aquatic toxicity and environmental fate showed that the major differences between FRs of concern and their proposed alternatives are the potential for bioaccumulation and CMR (carcinogenic, mutagenic or reprotoxic) effects. As most alternatives are inorganic chemicals, persistence (alone) is not a suitable criterion.From our experiences in carrying out a CAA we conclude: i) REACH registration dossiers provide a comprehensive source of hazard information for an alternative assessment. It is important to consider that the presented data is subject to changes and its quality is variable. ii) Correct identification of the chemicals is crucial to retrieve the right data. This can be challenging for mixtures, reaction products or nanomaterials or when only trade names are available. iii) The quality of the data and the practice on how to fill data gaps can have a huge impact on the results and conclusions. iv) Current assessment criteria have mainly been developed for organic chemicals and create challenges when applied to inorganic solids, including nanomaterials. It is therefore crucial to analyse and report uncertain...

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Section: Resultsmentioning

confidence: 99%

Chemical alternatives assessment of different flame retardants – A case study including multi-walled carbon nanotubes as synergist

Aschberger

Campia

Pesudo

et al. 2017

Environment International

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“…The Panel considers that, in general, inhalation exposure toxicity data cannot be extrapolated directly to an oral exposure situation. The Panel recognises that the approach taken here comprises route-toroute extrapolation, which is not trivial (Pepelko, 1987;Rennen et al, 2004). However, given the absence of toxicity in tissues of first (possible) contact, the limited metabolism, the fast distribution and excretion, and the non-reactive character of the substance in this particular case, the Panel considered it appropriate to evaluate the safety of the proposed used of this substance on the basis of the available inhalation toxicity data.…”

Section: Discussionmentioning

confidence: 99%

Scientific Opinion on the safety of use of dimethyl ether as an extraction solvent under the intended conditions of use and the proposed maximum residual limits

Flavourings¹

2015

EFS2

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Dimethyl ether was previously evaluated by the EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) and considered to give rise to no safety concerns under the conditions of use and the maximum residual limits proposed by the applicant. The present scientific opinion of the EFSA CEF Panel deals with the re-evaluation of the safety of dimethyl ether as an extraction solvent under new intended conditions of use and new maximum residual limits. The applicant requests a change in the residual limit of dimethyl ether in defatted animal protein products (in particular collagen) from 0.009 mg/kg to 3 mg/kg, and a new use for the extraction of protein products to yield gelatin with a residual limit of 0.009 mg/kg is also requested. The Panel notes the maximum residual limit requested by the applicant is much higher than the existing limit. Nonetheless, the margin of exposure for this new application is considered to be adequate. No new toxicity data were provided for dimethyl ether and, since the previous EFSA evaluation, only two in vitro genotoxicity studies have become available. These studies do not indicate any genotoxic potential for the assessed substance. The Panel thus considers that the use of dimethyl ether as an extraction solvent, under the intended conditions of use and with the proposed residual limits of 3 mg/kg in the defatted protein products and 9 μg/kg specifically in gelatin, is of no safety concern. More specifically, a re-evaluation was sought for the use of dimethyl ether under the new intended conditions of use and proposed maximum residual limits (MRL), namely: © European preparation of defatted animal protein products (collagen), MRL of 3 mg/kg in the defatted protein products; specific preparation of gelatin, MRL of 0.009 mg/kg in the gelatin.The Commission asked EFSA to issue a scientific opinion on the assessment of the safety of dimethyl ether when used as an extraction solvent for the preparation of defatted animal protein products. Specifically, the applicant proposes to use dimethyl ether in the preparation of collagen and gelatin. These products are used, amongst others, by the meat industry in the preparation of processed meat products and other food products. The used level of collagen is typically 2.0 % (w/w) of the finished product, but up to 3.5 % (w/w) may be used. For gelatin, the maximum use level in food is 9.0 % (w/w).Dimethyl ether toxicity has been tested mainly upon atmosphere exposure. Upon inhalation, dimethyl ether is rapidly taken up and distributed in various tissues and organs. It is reported that, upon exposure in the atmosphere to 1 000 ppm (equivalent to 1 884 mg/m 3 ) in rats, dimethyl ether levels of 14 to 22 mg/kg have been found in different organs and tissues. Organ distribution appears to be proportional with atmosphere concentrations in the range of 750 to 2 000 ppm (equivalent to a concentration in atmosphere of 1 413 and 3 768 mg/m 3 ).The Panel considers that, in general, inhalation exposure toxicity data c...

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“…The Panel recognizes that the approach taken here comprises route-to-route extrapolation, which is not trivial (Pepelko, 1987, Rennen et al, 2004. However, given the absence of toxicity in tissues of first (possible) contact, the limited metabolism and non-reactive character of the substance and the very large margin between the overall NOAEL and the anticipated maximum exposure, in this particular case the Panel considered it appropriate to evaluate the safety of the proposed used of this substance on the basis of the available inhalation toxicity data.…”

Section: Discussionmentioning

confidence: 99%

Safety in use of dimethyl ether as an extraction solvent

2009

EFS2

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Oral-to-inhalation route extrapolation in occupational health risk assessment: a critical assessment

Cited by 32 publications

References 11 publications

Chemical alternatives assessment of different flame retardants – A case study including multi-walled carbon nanotubes as synergist

Chemical alternatives assessment of different flame retardants – A case study including multi-walled carbon nanotubes as synergist

Scientific Opinion on the safety of use of dimethyl ether as an extraction solvent under the intended conditions of use and the proposed maximum residual limits

Safety in use of dimethyl ether as an extraction solvent

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