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Single-use plastics constitute approximately half of global plastic waste generation. Their use in consumer goods and packaging has been the focus of recent waste prevention policy due to the importance of the volumes of waste generated and the frequency with which these materials are littered. To address several externalities that emerge across the life-cycle of single-use plastics, multiple policies can be combined to constitute an effective policy mix. In several markets, market-based policy instruments and policy bans have helped to curb waste generation and littering of single-use plastics. However, the effectiveness of these interventions depends to an important extent on whether environmentally preferable substitute materials or products are available, and on whether the measures are effectively enforced. Effective policy intervention requires a policy mix that covers single-use plastics, as well as their substitutes, and that includes an emphasis on monitoring and enforcement, in order to help minimise burden-shifting of environmental impacts.

Microplastics are ubiquitous in the natural environment. This report synthesises the current state of knowledge on the sources, fate and risks of microplastics pollution. It then focuses on two sources of microplastics pollution, textile products and vehicle tyres, due to their substantial contribution to global microplastics emissions and currently largely absent policy frameworks to mitigate them. Several best practices and technological solutions can be implemented along the lifecycle of textile products and vehicle tyres to mitigate releases to the environment. The report proposes policy insights on measures and strategies that could help minimise microplastics emitted unintentionally from products and their potential impacts on human health and ecosystems.

The present AOP describes inhibition of histone deacetylase resulting in testicular atrophy. Histone deacetylase inhibitors (HDIs) are approved as anti-cancer drugs since HDIs have apoptotic effects in cancer cells. The intracellular mechanisms of induction of the spermatocyte apoptosis by HDIs are suggested as histone deacetylase (HDAC) inhibition as MIE, histone acetylation increase, disrupted cell cycle, apoptosis, and spermatocyte depletion as KEs. The adverse outcome has been defined as testicular atrophy. The HDIs inhibit deacetylation of the histone, leading to an increase in histone acetylation. The apoptosis induced by disrupted cell cycle leads to spermatocyte depletion and testis atrophy. Testicular toxicity is of interest for human health risk assessment especially in terms of reproductive and developmental toxicity, however, the testicular toxicity has not been fully elucidated. This AOP may be one of the pathways induced by HDIs, which suggests the pathway networks of protein hyperacetylations.

The present AOP describes the inhibition of calcineurin activity resulting in impaired T-Cell Dependent Antibody Response (TDAR). Calcineurin (CN), a protein phosphatase, is known to impair immune function when its phosphatase activation is inhibited. CN inhibitors (CNIs) inhibit CN phosphatase activity to suppress many kinds of immune functions and have been used in the medical domain to prevent hyper immune reactions. However, CNIs are reported to also induce immunosuppression-derived adverse effects such as increased frequency and/or severity of infections and increased tumor incidences. CNIs might affect several T-cell derived immune functions to induce compromised host. Among the affected immune functions, T-cell dependent antibody response (TDAR) is an important factor to resist infections and thought to be the useful endpoint on evaluating immunotoxicity of chemicals; therefore, this AOP describes the linkage between the inhibition of CN activity and impairment of TDAR.

This report presents a comprehensive assessment of the policy instruments adopted by the Netherlands to reach carbon neutrality in its manufacturing sector by 2050. The analysis illustrates the strength of combining a strong commitment to raising carbon prices with ambitious technology support, uncovers the pervasiveness of competitiveness provisions, and highlights the trade-off between short-term emissions cuts and longer-term technology shift. The Netherlands’ carbon levy sets an ambitious price trajectory to 2030, but is tempered by extensive preferential treatment to energy-intensive users, yielding a highly unequal carbon price across firms and sectors. The country’s technology support focuses on the cost-effective deployment of low-carbon options, which ensures least-cost decarbonisation in the short run but favours relatively mature technologies. The report offers recommendations for policy adjustments to reach the country’s carbon neutrality objective, including the gradual removal of exemptions, enhanced support for emerging technologies and greater visibility over future infrastructure plans.

The present AOP describes the prolonged activation of Cyp2E1 resulting in liver cancer. Cyp2E1 is a cytochrome P450 mono-oxygenase that bioactivates over 85 substrates, thereby creating electrophilic metabolites and oxidative stress. Mono-oxygenation of these substrates to their reactive metabolites, and the accompanying oxidative stress produced during metabolism, pose health risks because they lead to hepatotoxicity and, often, to liver cancer. The MIE occurs when Cyp2E1 binds a substrate. The Cyp2E1 catalytic cycle is prone to decoupling, which produces oxidative stress (KE1), and mono-oxidation of substrates produces reactive metabolites. Both reactive oxygen species and metabolites cause cytotoxicity (KE2). However, following injury, the liver is able to regenerate itself through an increase in cellular proliferation (KE3). Under conditions of chronic activation of Cyp2E1, excessive chronic increases in levels of reactive oxygen species and cell death, and subsequent dysregulated cellular proliferation, leads to tumour formation (AO).

This report presents a comprehensive assessment of the policy instruments adopted by the Netherlands to reach carbon neutrality in its manufacturing sector by 2050. The analysis illustrates the strength of combining a strong commitment to raising carbon prices with ambitious technology support, uncovers the pervasiveness of competitiveness provisions, and highlights the trade-off between short-term emissions cuts and longer-term technology shift. The Netherlands’ carbon levy sets an ambitious price trajectory to 2030, but is tempered by extensive preferential treatment to energy-intensive users, yielding a highly unequal carbon price across firms and sectors. The country’s technology support focuses on the cost-effective deployment of low-carbon options, which ensures least-cost decarbonisation in the short run but favours relatively mature technologies. The report offers recommendations for policy adjustments to reach the country’s carbon neutrality objective, including the gradual removal of exemptions, enhanced support for emerging technologies and greater visibility over future infrastructure plans.