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 (CF-) or methylene (-CF-) 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.

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.

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.

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.

PARP-1 expression and activity in primary human lung cells.

Activation of poly(ADP-ribose) polymerase-1 (PARP-1) in response to DNA damage is an important mechanism to keep homeostasis or to trigger apoptosis. The expression and function of (PARP-1) was studied in primary cells cultured from human lung. Normal human bronchial epithelial cells (NHBEC) and peripheral lung cells (PLC) from lung cancer patients were grown as explant cultures and were followed over a period of 12 weeks.

[Responsibilities of the European Chemical Agency under REACH].

A new independent institution, the European Chemical Agency (ECHA), will be established after the new Regulation on Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) has come into effect, in order to ensure effective management at the community level. The Agency shall be managed by an executive director. The secretariat shall undertake all tasks related to the registration, the management of dossiers and the coordination of the evaluation of chemicals.

[Risk assessment and chemical safety under REACH].

Under the new European chemical legislation REACH (EG 1907/2006), dangerous properties of chemical substances will be evaluated and data gaps will be closed. This information is needed for other regulations, such as safety at the working place or for the safe handling of products. Existing knowledge on chemical compounds must be broadened because previous regulations have focused on high production volume compounds.

Cadmium, cobalt and lead cause stress response, cell cycle deregulation and increased steroid as well as xenobiotic metabolism in primary normal human bronchial epithelial cells which is coordinated by at least nine transcription factors.

Workers occupationally exposed to cadmium, cobalt and lead have been reported to have increased levels of DNA damage. To analyze whether in vivo relevant concentrations of heavy metals cause systematic alterations in RNA expression patterns, we performed a gene array study using primary normal human bronchial epithelial cells. Cells were incubated with 15 microg/l Cd(II), 25 microg/l Co(II) and 550 microg/l Pb(II) either with individual substances or in combination.

Arachidonic acid pathway activates multidrug resistance related protein in cultured human lung cells.

Primary cultures of human lung cells can serve as a model system to study the mechanisms underlying the effects of irritants in air and to get a deeper insight into the (patho)physiological roles of the xenobiotic detoxification systems. For 99 human lung cancer cases the culture duration for bronchial epithelium and peripheral lung cells (PLC) are given in term of generations and weeks. Using this system, we investigated whether and how prostaglandins (PG) modify multidrug resistance related protein (MRP) function in normal human lung cells.

Non-destructive micromethod for MRP1 functional assay in human lung tumor cells.

Defense against toxic endo- and xenobiotics is a major concern of all living species and ABC transporters play a vital role in this defense system. Multidrug resistance associated proteins 1 (MRP1) is a cellular detoxifying factor supposed to transport a wide range of compounds across cell membranes either as GSH conjugates or as co-transport accompanying glutathione transposition. The cellular localization of MRP1 is a determining factor whether the transport function can take place.

Expression of lung resistance-related protein, LRP, and multidrug resistance-related protein, MRP1, in normal human lung cells in long-term cultures.

Transport processes form part of the body's defense mechanism, and they determine the intracellular levels of many endogenous and exogenous compounds. The multidrug resistance-related protein MRP1 and the lung resistance-related protein LRP are associated with drug resistance against chemotherapeutics; they protect cells against toxic compounds. There is much experimental evidence to suggest that both of these transporter proteins serve important physiological functions.

New aspects in the classification of carcinogens.

The existing systems of classification of carcinogens should include a distinction between genotoxic and non-genotoxic chemicals. For non-genotoxic chemicals, permissible exposure levels can be derived at which no relevant human cancer risks are anticipated. While genotoxic carcinogens can induce chromosomal effects without mutagenic action, non-DNA-reactive genotoxins affecting topoisomerase or the spindle, or those having an exclusively aneugenic effect can be carcinogenic only at high, toxic doses.

Immuno-histochemical detection of MRPs in human lung cells in culture.

The transport of molecules across membranes is an essential function of all living organisms and a large number of specific transporters have evolved to carry out this function. The largest transporter gene family is the ATP-binding cassette (ABC) transporter superfamily. The multidrug resistance-associated protein (MRP) family is comprised of nine related ABC transporters.

Response of rat alveolar type II cells and human lung tumor cells towards oxidative stress induced by hydrogen peroxide and paraquat.

The expression of MDR1b coding mRNA is increased in alveolar type II cells from juvenile rat lung in culture. Hydrogen peroxide and paraquat-induced further upregulation supporting that oxidative stress mediated mechanisms are involved in the regulation of MDR1b in rat lung. The expression rates of mRNA for catalase, Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and Mn-superoxide dismutase (Mn-SOD) remains constant during culture and were not modulated by hydrogen peroxide or paraquat.

Carcinogenicity categorization of chemicals-new aspects to be considered in a European perspective.

Existing systems of classification of carcinogens are a matter of discussion, world-wide. There is agreement that it should be distinguished between genotoxic and non-genotoxic chemicals. The risk assessment approach used for non-genotoxic chemicals is similar among different regulatory bodies: insertion of an uncertainty (safety) factor permits the derivation of permissible exposure levels at which no relevant human cancer risks are anticipated.