AI and ML-based risk assessment of chemicals: predicting carcinogenic risk from chemical-induced genomic instability.

Chemical risk assessment plays a pivotal role in safeguarding public health and environmental safety by evaluating the potential hazards and risks associated with chemical exposures. In recent years, the convergence of artificial intelligence (AI), machine learning (ML), and omics technologies has revolutionized the field of chemical risk assessment, offering new insights into toxicity mechanisms, predictive modeling, and risk management strategies. This perspective review explores the synergistic potential of AI/ML and omics in deciphering clastogen-induced genomic instability for carcinogenic risk prediction.

Atmospheric concentrations of per- and polyfluoroalkyl substances and their emissions at a waste recycling facility producing refuse-derived paper and plastics densified fuel.

To better understand the types and concentrations of per- and polyfluoroalkyl substances (PFAS) emitted into the air from waste recycling facilities that produce refuse-derived paper and plastics densified fuel (RPF) from industrial waste, we conducted an air sampling campaign at a waste recycling facility in Japan. Both passive and active air sampling were conducted, and the samples collected were used to quantify the PFAS emitted into the air during the production of RPF. Overall, few ionic PFAS were detected in the air at the facility; however, high levels of neutral PFAS (8.

Toxicokinetics of a developmental toxicity test in zebrafish embryos and larvae: Relationship with drug exposure in humans and other mammals.

To study the effects of drugs on embryo/fetal development (EFD), developmental and reproductive toxicity studies in zebrafish () embryos is expected to be an accepted alternative method to animal studies using mammals. However, there is a lack of clarity in the relationship between the concentration of developmental toxicity agents in whole embryos or larvae (Ce) and that in aqueous solution (Cw), and also between the amount of drug exposure required to cause developmental toxicity in zebrafish embryos or larvae and that required in mammals. Here, we measured Ce for developmental toxicity agents every 24 h starting at 24 h post fertilization (hpf).

Separation of the diastereomers of phosphorothioated siRNAs by anion-exchange chromatography under non-denaturing conditions.

In recent years, several small interfering RNA (siRNA) therapeutics have been approved, and most of them are phosphorothioate (PS)-modified for improving nuclease resistance. This chemical modification induces chirality in the phosphorus atom, leading to the formation of diastereomers. Recent studies have revealed that Sp and Rp configurations of PS modifications of siRNAs have different biological properties, such as nuclease resistance and RNA-induced silencing complex (RISC) loading.

Lack of in vivo mutagenicity of carbendazim in the liver and glandular stomach of MutaMice.

Background: Carbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity, carbendazim is deemed to be non-mutagenic in vitro, but it causes indicative DNA damage in vivo and chromosome aberrations in vitro and in vivo. In this study, we examined the mutagenicity of carbendazim in vivo.

Proof of concept testing of a positive reference material for in vivo and in vitro sensitization testing of medical devices.

In vivo skin sensitization tests are required to evaluate the biological safety of medical devices in contact with living organisms to provide safe medical care to patients. Negative and positive reference materials have been developed for biological tests of cytotoxicity, implantation, hemolysis, and in vitro skin irritation. However, skin sensitization tests are lacking.

Single intratracheal administration toxicity study on safety of vapor inhalation of electrolyzed reduced water in rats.

The effects of acute intratracheal administration of electrolyzed reduced water (ERW; alkaline electrolyzed water) were investigated in rats. In this study, no deaths or near-deaths were recorded in either group, namely those treated with ERW or purified water (maximum doses of 900 mg/kg). The main symptoms observed in the rats were decreased spontaneous movements and abnormal breath sounds, which were considered to be transient symptoms caused by intratracheal administration.

High-pH mobile phase in reversed-phase liquid chromatography-tandem mass spectrometry to improve the separation efficiency of aminoglycoside isomers.

In chromatography, the use of extreme conditions can often lead to unique separation selectivity. In this study, a highly basic mobile phase (pH > 11), which is not typically employed for reversed-phase liquid chromatography (RPLC), was utilized in RPLC-tandem mass spectrometry (MS/MS) to achieve effective separation between electrically neutral bases of aminoglycosides (AGs). A mixture of AGs was simultaneously analyzed using 500 mmol L ammonia aqueous solution (pH 11.

Modified ESR-based photosafety test (ESR-PT) detecting singlet oxygen and free radical formation.

The electron spin resonance-based photosafety test (ESR-PT) was modified using a new parameter, photoreactivity index (PRI), to detect singlet oxygen and free radical photoproducts simultaneously. With this modification, the modified ESR-PT is expected to reduce the number of false negative results due to chemicals producing free radical photoproducts other than singlet oxygen. The assay performance of the modified ESR-PT was evaluated using 56 chemicals, including hydrophobic chemicals.

In vivo mutagenicity assessment of orally treated tert-butyl hydroperoxide in the liver and glandular stomach of MutaMouse.

Background: tert-Butyl hydroperoxide (TBHP; CAS 75-91-2), a hydroperoxide, is mainly used as a polymerization initiator to produce polyethylene, polyvinyl chloride, and unsaturated polyester. It is a high-production chemical, widely used in industrial countries, including Japan. TBHP is also used as an additive for the manufacturing of food utensils, containers, and packaging (UCP).

Statistical Post-Processing Method for Evaluating Bioaccumulation in Fish Due to Dietary Exposure in Japan.

In 2018, the dietary exposure bioaccumulation fish test of the Organization for Economic Co-operation and Development Test Guideline No. 305 was introduced into Japan's Chemical Substances Control Law. The Japanese government has adopted a single definitive testing criterion for the absence of high bioaccumulation: the growth-corrected kinetic dietary magnification factor (BMF) must be less than 0.

The inter-laboratory validation study of EpiSensA for predicting skin sensitization potential.

The Epidermal Sensitization Assay (EpiSensA) is a reconstructed human epidermis (RhE)-based gene expression assay for predicting the skin sensitization potential of chemicals. Since the RhE model is covered by a stratified stratum corneum, various kinds of test chemicals, including lipophilic ones and pre-/pro-haptens, can be tested with a route of exposure akin to an in vivo assay and human exposure. This article presents the results of a formally managed validation study of the EpiSensA that was carried out by three participating laboratories.

Degradation of p0071 and p120-catenin during adherens junction disassembly by .

disseminates hematogenously to reach the target organs by disrupting epithelial adherens junctions (AJs), thus causing leptospirosis, which is a globally neglected zoonotic disease. induces E-cadherin (E-cad) endocytosis and cytoskeletal rearrangement during AJ disassembly, but the detailed mechanism remains unknown. Elucidation of AJ disassembly mechanisms will guide new approaches to developing vaccines and diagnostic methods.

Comparison of the acceptable surface limits derived from the skin sensitization potency for workers and swab residue limits determined from the permitted daily exposure derived from the systemic effects.

Allergic contact dermatitis is a common occupational and environmental health problem and setting of health-based exposure limits (HBELs) to prevent induction of skin sensitization is strongly desired. When manufacturing pharmaceuticals in a shared facility, cleaning validation using surface residue levels (SRLs) derived from permitted daily exposures (PDEs) is conducted to avoid cross-contamination from the perspective of protecting patients; however, it is unclear whether the SRLs are sufficient to prevent induction of skin sensitization for workers as well. In this study, we compared acceptable surface limits (ASLs) derived from acceptable exposure levels (AELs) based on EC1.

Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test.

Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.

Effects of inhalation of multi-walled carbon nanotube (MWCNT) on respiratory syncytial virus (RSV) infection in mice.

Multi-walled carbon nanotubes (MWCNTs), a kind of nanomaterial, are widely used in battery electrodes and composite materials, but the adverse effects associated with their accumulation in the living body have not been sufficiently investigated. MWCNTs are a fibrous material with molecules similar to asbestos fibers, and there are concerns about its effects on the respiratory system. In this study, we conducted a risk assessment by exposing mice using a previously developed nanomaterial inhalation exposure method.

Development of a HPLC system using a phase-separation multiphase flow as an eluent coupled to a silica-particle packed column.

The study reports the development of a high-performance liquid chromatography (HPLC) system in which a phase-separation multiphase flow as the eluent and a silica-particle based packed column as the separation column were combined to form the phase separation mode. Twenty-four types of mixed solutions of water/acetonitrile/ethyl acetate and water/acetonitrile were applied as eluents to the system at 20 °C. 2,6-Naphthalenedisulfonic acid (NDS) and 1-naphthol (NA) were injected as model analytes into the system.

Derivation of subacute guidance values for chemical contaminants of drinking water quality standard in Japan.

The concentration of chemicals in drinking water may transiently and accidently exceed the Drinking Water Quality Standard (DWQS). If the level of a contaminant is not expected to cause adverse effects for a limited period of exposure, immediate suspension of the water supply may not be necessary. Assessments should be conducted using subacute guidance values (SGVs).

In vivo mutagenicity assessment of styrene in MutaMouse liver and lung.

Background: Styrene (CAS 100-42-5) is widely used as polystyrene and acrylonitrile-butadiene-styrene resin such as plastic, rubber, and paint. One of the primary uses of styrene is food utensils and containers, but a small amount of styrene transferred into food can be ingested by eating. Styrene is metabolized into styrene 7,8-oxide (SO).

Augmentation of Pectoral Fin Teratogenicity by Thalidomide in Human Cytochrome P450 3A-Expressing Zebrafish.

The pharmacological and toxicological effects of active metabolites of enzymes including cytochrome P450 (CYP) are important. While it has been believed for a long time that thalidomide causes characteristic limb malformation only in rabbits and primates including humans, the involvement of their CYP3A subtypes (CYP3As) has been suggested. Recently, however, it was reported that zebrafish were sensitive to thalidomide, showing defects of pectoral fins, homologous organs of forelimbs in mammals, as well as other deformities.

Retrospective quantitative risk assessment of skin sensitization caused by an antimicrobial agent used in a consumer product: 2,3,5,6-Tetrachloro-4-(methylsulfonyl) pyridine.

Background: Serious cases of allergic contact dermatitis (ACD) caused by exposure to 3,5,6-tetrachloro-4-(methylsulfonyl)pyridine (TCMSP; CAS no. 13108-52-6) used as an antimicrobial agent for desk mats have been reported in Japan.

Objective: A quantitative risk assessment (QRA) of TCMSP contained in desk mats was performed retrospectively.