PFASs-restriction proposal commentary on ECHA's Annex XV restriction report, proposal for a restriction, March 2023.

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.

Absorption, distribution, metabolism, and excretion of methylene diphenyl diisocyanate and toluene diisocyanate: Many similarities and few differences.

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.

Long-term simulation of lead concentrations in agricultural soils in relation to human adverse health effects.

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.

A Review of the Environmental Degradation, Ecotoxicity, and Bioaccumulation Potential of the Low Molecular Weight Polyether Polyol Substances.

"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.

The Environmental Behavior of Methylene-4,4'-dianiline.

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.

High exposure to inorganic arsenic by food: the need for risk reduction.

Arsenic is a human carcinogen that occurs ubiquitously in soil and water. Based on epidemiological studies, a benchmark dose (lower/higher bound estimate) between 0.3 and 8 µg/kg bw/day was estimated to cause a 1 % increased risk of lung, skin and bladder cancer. A recently published study by EFSA on dietary exposure to inorganic arsenic in the European population reported 95th percentiles (lower bound min to upper bound max) for different age groups in the same range as the benchmark dose. For toddlers, a highly exposed group, the highest values ranged between 0.61 and 2.09 µg arsenic/kg bw/day. For all other age classes, the margin of exposure is also small. This scenario calls for regulatory action to reduce arsenic exposure. One priority measure should be to reduce arsenic in food categories that contribute most to exposure. In the EFSA study the food categories 'milk and dairy products,' 'drinking water' and 'food for infants' represent major sources of inorganic arsenic for infants and also rice is an important source. Long-term strategies are required to reduce inorganic arsenic in these food groups. The reduced consumption of rice and rice products which has been recommended may be helpful for a minority of individuals consuming unusually high amounts of rice. However, it is only of limited value for the general European population, because the food categories 'grain-based processed products (non rice-based)' or 'milk and dairy products' contribute more to the exposure with inorganic arsenic than the food category 'rice.' A balanced regulatory activity focusing on the most relevant food categories is required. In conclusion, exposure to inorganic arsenic represents a risk to the health of the European population, particularly to young children. Regulatory measures to reduce exposure are urgently required.

Manufactured nanomaterials: categorization and approaches to hazard assessment.

Nanotechnology offers enormous potential for technological progress. Fortunately, early and intensive efforts have been invested in investigating toxicology and safety aspects of this new technology. However, despite there being more than 6,000 publications on nanotoxicology, some key questions still have to be answered and paradigms need to be challenged. Here, we present a view on the field of nanotoxicology to stimulate the discussion on major knowledge gaps and the critical appraisal of concepts or dogma. First, in the ongoing debate as to whether nanoparticles may harbour a specific toxicity due to their size, we support the view that there is at present no evidence of 'nanospecific' mechanisms of action; no step-change in hazard was observed so far for particles below 100 nm in one dimension. Therefore, it seems unjustified to consider all consumer products containing nanoparticles a priori as hazardous. Second, there is no evidence so far that fundamentally different biokinetics of nanoparticles would trigger toxicity. However, data are sparse whether nanoparticles may accumulate to an extent high enough to cause chronic adverse effects. To facilitate hazard assessment, we propose to group nanomaterials into three categories according to the route of exposure and mode of action, respectively: Category 1 comprises nanomaterials for which toxicity is mediated by the specific chemical properties of its components, such as released ions or functional groups on the surface. Nanomaterials belonging to this category have to be evaluated on a case-by-case basis, depending on their chemical identity. Category 2 focuses on rigid biopersistent respirable fibrous nanomaterials with a specific geometry and high aspect ratio (so-called WHO fibres). For these fibres, hazard assessment can be based on the experiences with asbestos. Category 3 focuses on respirable granular biodurable particles (GBP) which, after inhalation, may cause inflammation and secondary mutagenicity that may finally lead to lung cancer. After intravenous, oral or dermal exposure, nanoscaled GBPs investigated apparently did not show 'nanospecific' effects so far. Hazard assessment of GBPs may be based on the knowledge available for granular particles. In conclusion, we believe the proposed categorization system will facilitate future hazard assessments.

A Novel Sampling Device for the Quantification of Primary Aromatic Amines on Surfaces.

Primary aromatic amines (PAAs) are a class of hazardous substances where many compounds are classified as carcinogen, mutagen, and reproduction toxin (CMR). PAAs can be taken up by dermal exposure. In the polyurethane industry, a valid and trustworthy method for the quantification of PAAs in the presence of isocyanates that could interfere is of great interest, especially on workplaces where a regular contact to PAAs cannot be excluded. The aim of this work is the development, validation, and verification of a novel sampling device to quantify selectively the PAA load on work surfaces. We describe the synthesis of Cell-ßALA-PEMSA analytical papers and their characterization by infrared spectroscopy and thermogravimetric analysis. The recovery of TDA and MDA spiked on these filters is satisfactory. An excellent selectivity of Cell-ßALA-PEMSA papers towards PAAs in the presence of isocyanates of almost 100% was found by wipe tests of amine/isocyanate contaminated surfaces. First positive field tests were achieved at certain areas in a Polyurethane Technical Application Department where surface contamination with PAAs was expected, and the Cell-ßALA-PEMSA analytical papers were superior to an established method of surface sampling. However, recovery of these amines from surfaces shows a large variability, and more work is required to address influencing surface properties.

Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from polyurethane flexible foam.

Polyurethanes (PU) are polymers made from diisocyanates and polyols for a variety of consumer products. It has been suggested that PU foam may contain trace amounts of residual toluene diisocyanate (TDI) monomers and present a health risk. To address this concern, the exposure scenario and health risks posed by sleeping on a PU foam mattress were evaluated. Toxicity benchmarks for key non-cancer endpoints (i.e., irritation, sensitization, respiratory tract effects) were determined by dividing points of departure by uncertainty factors. The cancer benchmark was derived using the USEPA Benchmark Dose Software. Results of previous migration and emission data of TDI from PU foam were combined with conservative exposure factors to calculate upper-bound dermal and inhalation exposures to TDI as well as a lifetime average daily dose to TDI from dermal exposure. For each non-cancer endpoint, the toxicity benchmark was divided by the calculated exposure to determine the margin of safety (MOS), which ranged from 200 (respiratory tract) to 3×10(6) (irritation). Although available data indicate TDI is not carcinogenic, a theoretical excess cancer risk (1×10(-7)) was calculated. We conclude from this assessment that sleeping on a PU foam mattress does not pose TDI-related health risks to consumers.

Decontamination of disposable respirators for reuse in a pandemic employing in-situ-generated peracetic acid.

BACKGROUND: During shortages of filtering face pieces (FFP) in a pandemic, it is necessary to implement a method for safe reuse or extended use. Our aim was to develop a simple, inexpensive and ecological method for decontamination of disposable FFPs that preserves filtration efficiency and material integrity. MATERIAL AND METHODS: Contamination of FFPs (3M Aura 9320+) with SARS-CoV-2 (1.15 × 104 PFUs), Enterococcus faecium (>106 CFUs), and physiological nasopharyngeal flora was performed prior to decontamination by submersion in a solution of 6 % acetic acid and 6 % hydrogen peroxide (6%AA/6%HP solution) over 30 minutes. Material integrity was assessed by testing the filtering efficiency, loss of fit and employing electron microscopy. RESULTS AND DISCUSSION: Decontamination with the 6%AA/6%HP solution resulted in the complete elimination of SARS-CoV-2, E. faecium and physiological nasopharyngeal flora. Material characterization post-treatment showed neither critical material degradation, loss of fit or reduction of filtration efficiency. Electron microscopy revealed no damage to the fibers, and the rubber bands' elasticity was not affected by the decontamination procedure. No concerning residuals of the decontamination procedure were found. CONCLUSION: The simple application and widespread availability of 6%AA/6%HP solution for decontaminating disposable FFPs make this solution globally viable, including developing and third world countries.

VOC emissions from particle filtering half masks - methods, risks and need for further action.

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.

Derivation of indoor air guidance values for volatile organic compounds (VOC) emitted from polyurethane flexible foam: VOC with repeated dose toxicity data.

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.

Read across for the derivation of Indoor Air Guidance Values supported by PBTK modelling.

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.

Toxicological risk at workplace and toxicity as Life Cycle Assessment impact category: Substitution of solvents as an example.

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.

Benzene and its methyl-derivatives: derivation of maximum exposure levels in automobiles.

Automobile drivers are exposed to several organic hydrocarbons. Concentrations measured in passenger compartments have been reported to range between 13 and 560 microg/m(3) for benzene, 33-258 microg/m(3) for toluene, 20-250 microg/m(3) for xylene (mixed isomers) and 3-23 microg/m(3) for trimethylbenzene (mixed isomers). These aromatic hydrocarbons are emitted from gasoline and from materials inside a car. In the present study we evaluated, whether these exposures pose a potential risk to the health of drivers. Therefore, we derived maximum exposure levels inside cars for chronic (ELIA(chronic)) and short-term (STELIA) exposure. The lowest ELIA's(chronic) for benzene, toluene, xylene and trimethylbenzene were 0.083, 1.2, 8.8 and 0.31 mg/m(3), respectively. The respective STELIA's were 16, 30, 29 and 25 mg/m(3). Obviously concentrations of toluene, xylene and trimethylbenzene inside cars do not exceed their individual STELIA's. In contrast, benzene seems to be problematic, since concentrations inside cars amount up to 0.56 mg/m(3), which exceeds the ELIA(chronic) derived for benzene. This should not be underestimated, since benzene is a genotoxic carcinogen that probably acts by non-threshold mechanisms. In conclusion, concentrations of toluene, xylene and trimethylbenzene usually observed inside cars are unlikely to pose a risk to the health of drivers. A systematic toxicological evaluation of the risk associated with benzene exposure in cars seems to be necessary.

Maximum exposure levels for xylene, formaldehyde and acetaldehyde in cars.

Although millions of individuals are exposed to emissions from articles inside cars, relatively little has been published about possible adverse health effects and about exposure levels that can be considered safe or "acceptable". Xylene, formaldehyde and acetaldehyde represent typical examples of relevant volatile organic substances (VOC) released from articles inside cars. Recently, a concept for derivation of maximum exposure levels for volatile organic substances in cars has been published. In the present study we applied this concept to derive maximum exposure levels for xylene, formaldehyde and acetaldehyde and compared the resulting concentrations to exposure levels usually found inside of cars. We derived Short Term Exposure Levels Inside Automotive Vehicles (STELIA) of 29, 0.125 and 15.3 mg/m(3) for xylene, formaldehyde and acetaldehyde, respectively. These STELIAs should not be exceeded during short-term exposures, for instance when starting a car that had been heated up during parking in the sun. Exposure Levels Inside Automotive Vehicles (ELIA, chronic) for chronic exposure to non-genotoxic substances were 8.8, 0.125 and 0.635 mg/m(3) for systemic as well as 17.6, 0.125 and 1.7 mg/m(3) for local exposure to xylene, formaldehyde and acetaldehyde, respectively. Although, it is known that exposure limits for carcinogenic substances should be treated with caution, encouraged by the well documented threshold mechanisms we nevertheless derived ELIAs for Carcinogenic and Mutagenic Substances (ELIA, cm) resulting in 0.125 and 0.635 mg/m(3) for formaldehyde and acetaldehyde. If these ELIAs are matched against average concentrations of xylene, formaldehyde and acetaldehyde found in cars at 23 degrees C (1.22, 0.048 and 0.042 mg/m(3)), there is no reason for concern. With respect to STELIAs and extrapolated concentrations at 65 degrees C (14.7, 1.47 and 1.68 mg/m(3), for xylene, formaldehyde and acetaldehyde, respectively), however, a reduction of the concentration of formaldehyde may be necessary.

Characterization of the biosynthetic gene cluster for the antifungal polyketide soraphen A from Sorangium cellulosum So ce26.

A genomic DNA region of over 80 kb that contains the complete biosynthetic gene cluster for the synthesis of the antifungal polyketide metabolite soraphen A was cloned from Sorangium cellulosum So ce26. The nucleotide sequence of the soraphen A gene region, including 67,523 bp was determined. Examination of this sequence led to the identification of two adjacent type I polyketide synthase (PKS) genes that encode the soraphen synthase. One of the soraphen A PKS genes includes three biosynthetic modules and the second contains five additional modules for a total of eight. The predicted substrate specificities of the acyltransferase (AT) domains, as well as the reductive loop domains identified within each module, are consistent with expectations from the structure of soraphen A. Genes were identified in the regions flanking the two soraphen synthase genes that are proposed to have roles in the biosynthesis of soraphen A. Downstream of the soraphen PKS genes is an O-methyltransferase (OMT) gene. Upstream of the soraphen PKS genes there is a gene encoding a reductase and a group of genes that are postulated to have roles in the synthesis of methoxymalonyl-acyl carrier protein (ACP). This unusual extender unit is proposed to be incorporated in two positions of the soraphen polyketide chain. One of the genes in this group contains distinct domains for an AT, an ACP, and an OMT.

New insights into rifamycin B biosynthesis: isolation of proansamycin B and 34a-deoxy-rifamycin W as early macrocyclic intermediates indicating two separated biosynthetic pathways.

Proansamycin B, the formerly postulated intermediate of rifamycin B biosynthesis, was isolated from cultures of the Amycolatopsis mediterranei mutant F1/24. The structure was determined using UV, IR, NMR and MS techniques. Biotransformation studies demonstrate that proansamycin B is an intermediate of a shunt pathway, a 8-deoxy variant, of rifamycin B biosynthesis leading to 8-deoxy-rifamycin B as the final product. In addition, 34a-deoxy-rifamycin W, the direct precursor of rifamycin W, could be isolated representing the earliest macrocyclic intermediate obtained so far in the biosynthetic route to rifamycin B. Furthermore, the new rifamycin W-28-desmethyl-28-carboxy and rifamycin W-hemiacetal, intermediates in the transformation sequence of rifamycin W to rifamycin S, were isolated. Application of proton NMR measurements (double resonance and ROESY experiments) on the latter compound indicated that the stereochemistry at the chiral center C-28 is R.

Argyrins, immunosuppressive cyclic peptides from myxobacteria. I. Production, isolation, physico-chemical and biological properties.

A group of cyclic peptides consisting of 8 amino acid residues, named argyrins A to H, were isolated from the culture broth of strains of the myxobacterium Archangium gephyra. Argyrin B was found to be a potent inhibitor of T cell independent antibody formation by murine B cells and strongly inhibited the two way murine mixed lymphocyte reaction. All argyrins had slight antibiotic activity, especially against Pseudomonas sp., and inhibited growth of mammalian cell cultures. The growth inhibition was often incomplete and varied highly with different cell lines.

Modeling formation and distribution of toluene-2,4-diamine (TDA) after spillage of toluene-2,4-diisocyanate (TDI) into a river.

Toluene diisocyanate (TDI) is a large volume chemical used for the production of polyurethanes. It is sparingly soluble in water, but hydrolyses instantaneously liberating toluene diamine (TDA), which is highly reactive to TDI. The ecotoxicity of TDI is dominated by TDA. The hydrolysis of TDI under static and dynamic conditions was investigated previously. Previously published data on TDI hydrolysis were re-visited, and based on these data a model was developed that allows a conservative and quick estimation of TDA concentrations in rivers following a major incident with TDI. As earlier published model experiments indicate, the maximum achievable TDA concentration is about 30 mg/L. Model simulations based on these experiments indicate that the TDA concentrations in a river after TDI discharge may be up to three orders of magnitude lower.