Thomas Schupp

PFASs are defined as substances that contain at least one fully fluorinated methyl (CF₃–) or methylene (–CF₂–) carbon atom. The excellent technical properties of members of the PFAS group have led to their use in a wide range of applications. The substance group comprises more than 10,000 individual compounds. A variety of adverse effects has been described for single substances. For the majority of the PFASs, neither toxicokinetic data nor effect data is available. Hence, because of the small number of PFASs for which a full toxicological profile is available, grouping based on the existing data is not feasible. A critical problem of PFASs and their degradation products is the very high persistence, which clearly fulfils the criterion for the substance property Very Persistent (vP) according to Annex XIII of the REACH Regulation. Because of this property the European Commission is planning to take action. Defining suitable subgroups appears to be a scientifically based approach. However, to reach this goal, large data gaps would have to be closed which would take up to centuries, a time-frame, which is not defendable with respect to potential irreversible harm. Because of the time pressure resulting from the potential irreversible harm, the precautionary principle has been selected as an appropriate tool to handle PFASs and in the restriction proposal PFASs are treated as one group. This approach is justified in the view of the advisory committee of the German Society for Toxicology. ECHA’s proposal received a lot of attention in the public. However, communication so far has obviously led to the misunderstanding of a proven health hazard for all PFASs. Communication should explain the justification of the broad inclusion of substances as being based on the precautionary principle. Data gaps versus current knowledge need to be clearly communicated; communication should also include the possibility for derogation of essential use. It should address the issue of suitable substitutes to avoid unintended health consequences; and it should mention that existing persistent environmental contamination calls for developing innovation in remediation techniques.

Methylene diphenyl diisocyanate (MDI) and toluene diisocyanate (TDI) are high production volume chemicals used for the manufacture of polyurethanes. For both substances, the most relevant adverse health effects after overexposure in the workplace are isocyanate-induced asthma, lung function decrement and, to a much lesser extent, skin effects. Over the last two decades many articles have addressed the reactivity of MDI and TDI in biological media and the associated biochemistry, which increased the understanding of their biochemical and physiological behavior. In this review, these new insights with respect to similarities and differences concerning the adsorption, distribution, metabolism, and excretion (ADME) of these two diisocyanates and the implications on their toxicities are summarized. Both TDI and MDI show very similar behavior in reactivity to biological macromolecules, distribution, metabolism, and excretion. Evidence suggests that the isocyanate (NCO) group is scavenged at the portal-of-entry and is not systemically available in unbound reactive form. This explains the lack of other than portal-of-entry toxicity observed in repeated-dose inhalation tests.

Investigations into volatile organic compound (VOC) emissions from polymer fleeces used in particle filtering half masks were conducted and evaluated against the German hygienic guide value for total volatile organic compounds and the “Lowest Concentration of Interest” for construction products. All masks showed emission of Xylene. In 94 % of samples, up to 24 additional aromatic compounds were found. 17 % of samples showed terpenes, 53 % emitted aldehydes, 77 % exhibited caprolactam and 98 % released siloxanes. All masks exceeded the TVOC hygienic guidance value level 5 of 10 mg/m³. Emission levels were investigated for masks immediately after their packages were opened and for masks that were “vented” for two weeks. Further, the emissions were repeatedly measured to investigate the decrease of emissions. An exponential decline was observed and a fitting function was calculated. The influence of the two commonly gas chromatograph (GC) hyphenated detectors, mass spectrometer (MS) and flame ionization detector (FID) on the VOC quantification, as well as the influence of temperature on the emission of VOCs were investigated. A statistical analysis of emission value differences for Notified Bodies was conducted and CE 2163 and 2020-1XG proved to be outliers.

Lead (Pb) exposure of consumers and the environment has been reduced over the past decades. Despite all measures taken, immission of Pb onto agricultural soils still occurs, with fertilizer application, lead shot from hunting activities, and Pb from air deposition representing major sources. Little is known about the intermediate and long-term consequences of these emissions. To gain more insight, we established a mathematical model that considers input from fertilizer, ammunition, deposition from air, uptake of Pb by crops, and wash-out to simulate the resulting Pb concentrations in soil over extended periods. In a further step, human oral exposure by crop-based food was simulated and blood concentrations were derived to estimate the margin of exposure to Pb-induced toxic effects. Simulating current farming scenarios, a new equilibrium concentration of Pb in soil would be established after several centuries. Developmental neurotoxicity represents the most critical toxicological effect of Pb for humans. According to our model, a Pb concentration of ~ 5 mg/kg in agricultural soil leads to an intake of approximately 10 µg Pb per person per day by the consumption of agricultural products, the dose corresponding to the tolerable daily intake (TDI). Therefore, 5 mg Pb/kg represents a critical concentration in soil that should not be exceeded. Starting with a soil concentration of 0.1 mg/kg, the current control level for crop fields, our simulation predicts periods of ~ 50 and ~ 175 years for two Pb immission scenarios for mass of Pb per area and year [scenario 1: ~ 400 g Pb/(ha × a); scenario 2: ~ 175 g Pb/(ha × a)], until the critical concentration of ~ 5 mg/kg Pb in soil would be reached. The two scenarios, which differ in their Pb input via fertilizer, represent relatively high but not unrealistic Pb immissions. From these scenarios, we calculated that the annual deposition of Pb onto soil should remain below ~ 100 g/(ha × a) in order not to exceed the critical soil level of 5 mg/kg. We propose as efficient measures to reduce Pb input into agricultural soil to lower the Pb content of compost and to use alternatives to Pb ammunition for hunting.

Polyurethane Flexible Foams (PUF) are versatile materials used in upholstered furniture and bed mattresses. Due to the production procedure, fresh foams emit volatile organic compounds (VOC) which may contribute to indoor air exposure. To evaluate the risk for consumers, the VOC concentration measured in chamber tests can be matched against existing benchmarks for indoor air like “Richtwerte” (RW) of the German UBA (Umweltbundesamt), “Lowest Concentration of Interest” (LCI) for construction products or derived no effect levels (DNEL) for consumer inhalation exposure. In a previous paper a method for the derivation of Indoor Air Guidance Values (IAGV) for VOC without RW, LCI or DNEL was developed. The method described made use of a sufficient toxicological database. For substances with an insufficient database, read across to structural analogues is a way forward to estimate Indoor Air Guidance Values (IAGV). In this work a read across exercise, supported by an open source physiology based toxicokinetic (PBTK) modelling program is demonstrated. The use of enzyme kinetic data for phase I and phase II metabolism is discussed and areas for further work were identified. For two substances with very limited toxicological data, allyloxypropanol (isomer mixture of 1-allyloxy-2-propanol and 2-allyloxy-1-propanol) and 2,3-di-ethyl-2,3-dimethylsuccinodintrile, Tentative Indoor Air Guidance Values of 750 µg/m³ and 65 µg/m³ were derived.

Polyurethane Flexible Foams (PUF) are versatile materials used in upholstered furniture and bed mattresses. Due to the production procedure, fresh foams emit volatile organic compounds (VOC). Chamber tests issued by the European association of flexible polyurethane foam blocks manufacturers (EUROPUR) revealed certain levels of VOCs, and the emission rates are declining over time. To assess the risk associated to these VOCs which, as a consequence, might be detectable in indoor air where these PUF are used. To evaluate the risk for consumers, their concentration can be matched against existing benchmarks for indoor air. These benchmarks are, for example, guidance values derived by the Advisory Group for Indoor Air Guidance Values of the German UBA (RW-values), Lowest Concentrations of Interest (LCI) for building products, or against derived no effect levels (DNELs) for consumers, defined in registration dossiers under the European Regulation No. 1907/2006. In this paper, indoor air guidance values are derived for some VOCs which do have neither RW- nor LCI-values, and no DNELs for consumers. Substances covered are trimethylsilanol, fluorotrimethylsilane, chloropropanol, propanal, triethylenediamine and 2,2,3,3-tetramethyl succinodinitrile.

Methylene-4,4′-dianiline (MDA, CAS-No. 101–77-9) is a high production volume intermediate that is mainly processed to diisocyanates and finally polyurethanes. This review summarizes available data concerning the environmental behavior. When released into the environment, MDA distributes into water and subsequently sediment and soil compartments; the air is of little relevance, owed to the low vapor pressure and short atmospheric half-life, which renders MDA non-critical for long-range transport. Biodegradation data present a diverged picture; in some tests, MDA is not readily biodegradable or even not inherent biodegradable; in other tests, MDA turned out to be readily biodegradable (but failing the 10-d window). The history and composition of the inoculum used for testing seem to play an important role, which is underlined by good test results with adapted inoculum. In soil, initially a rapid mineralization is observed, which slows down within the first days due to competitive chemical absorption. The latter results in degradation rates comparable to that of natural organic matter. Under anaerobic conditions, mineralization is poor. Irreversible chemisorption occurs unless soils/sediments are highly reduced. Half-lives due to primary decay do not indicate MDA to be persistent according to the regulatory guidance used in then EU, Canada, or the USA; in Japan, however, due to test results in MITI degradation tests, MDA would be regarded as persistent. The identification of microbial MDA metabolites deserves further research. MDA is not bioaccumulative, but it is toxic to aquatic organisms and mammals. MDA in pore water of soils is rapidly adsorbed on the surface of plant roots. Test runs were too short to draw a final conclusion with regards to transport to stem, leaves, and fruits. Data from structurally similar compounds indicate that such transport would account for less than 1% of the root-adsorbed material.

“Polyalkylene glycol” is the name given to a broad class of synthetic organic chemicals which are produced by polymerization of one or more alkylene oxide (epoxide) monomers, such as ethylene oxide (EO) and propylene oxide (PO), with various initiator substances which possess amine or alcohol groups. A generalization of this polymerization reaction is illustrated in Fig. 1.

Substitution of hazardous substances against less hazardous ones is a central requirement of the European Chemical Regulation REACH (European Regulation 1907/2006/EC). Hazardous substances emitted from products may not only affect the worker; drift off and distribution in the environment may finally result in exposure of the general population. This potential threat to health is covered by the impact category “toxicity” in Life Cycle Assessments. In this paper, we present a case of a substitution of volatile organic compounds in a reactive varnish, and compare the “old” formulation with the “new” formulation against health risk to the worker, and concerning the Life Cycle Assessment impact category “toxicity”. The “old” formulation contained Naphtha (petroleum), hydrodesulfurized, heavy and Solvent naphtha (petroleum), light, aromatic. In the new formulation, both naphthas were replaced by n-Butylacetate, 1-Ethoxy-2-propyl acetate and Ethyl-3-ethoxy propionate. In the European Union, the naphthas are classified as mutagens and carcinogens category 1, officially. However, if benzene is below 0.1 %, registrants in the EU proposed to omit this classification, and todays naptha products on the market obviously have benzene contents below 0.1 %. On a first glance, the improvement for workplace safety introduced by the substitution, therefore, is comparatively small, as it is for toxicity in Life Cycle Assessment. However, when background knowledge concerning chemical production processes of naphtha is included, benzene below a content of 0.1 % needs to be taken into consideration, and the benefit of substitution is more obvious.

Concerning chronic toxicity, D. magna is the most sensitive species tested against MDA aquatic exposures, with a 21 days-NOEC of 0.00525 mg/L. Exposure of daphnids takes place via the aquatic phase. Other species of the same phylum (Arthropoda) appear to be less sensitive albeit with exposures via soil or sediment, with a 28 days-NOEC of 562 mg/kg d. w. soil (F. candida) and 41.3 mg/kg d. w. sediment (Hyalella azteca), for reproductive and survival endpoints, respectively. Also for acute toxicity, D. magna is more sensitive than the other species, with an 48 h-EC50 that spreads over two orders of magnitude, ranging from 0.019 to 2.7 mg/L. Fish show a more uniform reaction to MDA, with 96 h-LC50 ranging from about 20 to 60 mg/L; chronic data for fish are not available. Acute toxicity data for algae and cyanobacteria are in the range of 1–10 mg/L; based on growth rate, the 72 h-NOEC_r or E_rC₁₀ of MDA to algae is 0.3–9.3 mg/L. For sediment organisms, the black worm L. variegatus shows the highest sensitivity against MDA with a NOEC between ≤3.75 mg/kg and 30 mg/kg d. w., followed by the amphipod H. azteca. The lower sensitivity of L. variegatus in the second study compared to the first study is obviously attributable to the different feeding regimes (semi-continuous feeding against pre-spiked sediment). One argument might be that semi-continuous feeding allows the organisms to avoid the contaminated food. However, a change from semi-continuous feeding to sediment pre-spiked with nettle powder (Urtica sp.) results in an earlier and much stronger increase in ammonia concentration in the system. This became apparent after both studies on the blackworm were finalized. The ammonia 96 h-EC50 for the blackworm is 0.69 mg/L at pH = 8.2, and the 96 h-EC10 at pH = 8.2 is 0.33 mg/L (Hickey and Vickers, Arch Environ Contam Toxicol 26:292–298, 1994). As a result, the lower NOEC and LOEC in the second study with L. variegatus are probably attributable to interference by ammonia. MDA binds irreversibly to soil and sediment which may explain the general, but not uniform lower sensitivity of soil and sediment organisms against aquatic organisms. However, species with intense soil or sediment contact (L. variegatus and E. fetida) show in general lower NOEC values than those organisms with less direct contact (3.75 and 11.2 mg/kg d. w., respectively). On the one hand it may be hypothesized that this intense contact to soil bound MDA is one reason for the higher sensitivity; on the other hand, metabolic capacity against MDA of the organisms tested is unknown at this point in time and might as well explain differences in species sensitivity. For plants there are only acute data available, and in respect to acute toxicity L. sativa is more sensitive to MDA than E. fetida. Limited aquatic data available so far do not indicate that the toxicity of pMDA is different to MDA. In addition, the limited set of data generated with the marine M. macrocopa (crustacean), N. fustulum (diatom) and V. fisheri (bacteria) do not indicate that sea water organisms are more sensitive to MDA than fresh water organisms. In mammals, MDA is unlikely to interact with the endocrine sexual system; interaction with the adrenergic system cannot be ruled out, and effects of MDA on the thyroid hormone system have been demonstrated. MDA inhibits the thyroid peroxidase which might contribute to the thyroid gland tumors observed in chronic studies with rats and mice. Some anti-androgenic activity in in vitro studies with yeast cell did not prevail in in vivo studies with rats and mice.