Real-time hazard assessment of maize based on the chilling injury process -- Using a standard curve to establish a daily cumulative assessment method.

Cold damage caused by low temperatures is known as chilling injury (CI), and it has consistently been one of the primary meteorological disasters affecting maize. With ongoing global climate change, the issue of chilling injury is becoming more prominent, exhibiting new characteristics and presenting new challenges. Consequently, understanding the disaster process and conducting a more refined real-time chilling injury identification have become significant challenges. In this study, we divided maize planting areas into seven maturity types based on the accumulated temperature, constructed a standard curve of the daily accumulated temperature from 1991 to 2020, proposed real-time identification indicators based on the CI process, and developed a real-time CI hazard assessment model. The results indicated that the model can capture independent CI events and rapidly determine the location, intensity, duration and scope of CIs, thereby providing a basis for accurately understanding the impact of chilling injury and taking timely countermeasures. The combination of accumulated temperature standard curves for seven maturity types of maize and the CI curve was used to construct the CI daily scale identification indicator, ΔEAT. Judgment thresholds for the CI identification indicators at various maturity levels were obtained by correlating them with historical disaster data. The frequency and intensity of maize CI gradually increased from the extremely late-maturing zone to the extremely early-maturing zone, with the seeding and emergence periods being the peak periods for CI. The spatiotemporal evolution characteristics of the three different degrees of CI events in 1992, 2004, and 2017 were consistent with the historical disaster records. Northeastern Inner Mongolia and most of Heilongjiang were found to be high-hazard areas for maize CIs. The constructed daily CI identification indicators can accurately and rapidly identify maize CIs, providing practical and targeted guidance for combating these injuries.

Potential mammary carcinogens used in food contact articles: implications for policy, enforcement, and prevention.

Many nations have food contact material (FCM) legislation purporting to protect citizens from hazardous chemicals, often specifically by regulating genotoxic carcinogens. Despite such regulations, cancers that are associated with harmful chemical exposures are highly prevalent, especially breast cancer. Using the novel Key Characteristics of Toxicants framework, Kay et al. found 921 substances that are potential mammary carcinogens. By comparing Kay et al.'s chemicals list with our own Database on migrating and extractable food contact chemicals (FCCmigex), we found that 189 (21%) of the potential mammary carcinogens have been measured in FCMs. When limiting these results to migration studies published in 2020-2022, 76 potential mammary carcinogens have been detected to migrate from FCMs sold in markets across the globe, under realistic conditions of use. This implies that chronic exposure of the entire population to potential mammary carcinogens from FCMs is the norm and highlights an important, but currently underappreciated opportunity for prevention. Reducing population-wide exposure to potential mammary carcinogens can be achieved by science-based policy amendments addressing the assessment and management of food contact chemicals.

Are Hazard Assessment Methods in the Assessment of Chemical Alternatives Suitable for REACH?

The assessment of chemical alternatives for hazardous substances is an important prerequisite for avoiding regrettable substitution, and several methods have been developed in the past to perform such a hazard assessment for chemical alternatives. We investigate here whether GreenScreen, Cradle to Cradle, multiple-criteria decision analysis (MCDA), the Pollution Prevention Options Analysis System, the U.S. EPA Safer Choice Standard and Criteria, and the GHS column model 2020 from IFA use similar criteria for the evaluation of substances as Article 57 of the European chemicals regulation, REACH, and how suitable these methods are for assessing per- and polyfluoroalkyl substances. MCDA and GreenScreen were analyzed in detail using two different data sets. The results of the assessments show that none of the investigated hazard assessment methods use the same criteria as described in Article 57 of REACH. It was also not possible to parametrize multi-attribute value theory (MAVT), a commonly used MCDA method, to align with Article 57 of REACH by using the relatively simple objective hierarchy that has been proposed in previous publications. There is therefore an urgent need for a modified/new method that can be used in the future to assess organic substances that are used within the European Economic Area.

Assessing the risk of consuming fish from Kanyakumari (Tamil Nadu), India: An evaluative study on bioaccumulated heavy metals in different fish species using inductively coupled plasma mass spectrometry.

Environmental pollutants which are developing an alarming situation in the contemporary world captured attention in the present research. When it comes to food safety and security concerns it becomes an important field to be studied rigorously as food contributes majorly to human and animal health. The pollution of aquatic ecosystems by heavy metals (HMs) ultimately results in adverse effect on the food chain, which is covered in the current study. Fish is considered to be one of the main components of a balanced diet plate due to its high-quality protein, which sets it apart from other dietary sources. On the other hand, it is also susceptible to the absorption and bioaccumulation of HMs at toxic levels. In our study, we have considered three different species (Nemipterus japonicus, Oreochromis mossambicus, and Lates calcarifer) of fish collected from Kanyakumari, Tamil Nadu (India). Three organs namely liver, gill, and muscle were taken into consideration for the HM profiling using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The Arsenic (As), Cadmium (Cd), Chromium (Cr), Mercury (Hg) and Lead (Pb) were found to be in varied concentrations ranging from 0.1 to 1.13, 0.89-1.45, 9.95-30.66, 0.14-1.62, and 24.69-189.5 µg/kg respectively, in the studied organs of fish. Carcinogenic and noncarcinogenic risk assessments were also done indicating a notable level of Pb and Cr in selected fish species. The Hazard Index (HI) for Oreochromis mossambicus was >1 for adults and children, indicating future possibility of probable health hazards on daily consumption of these fish. In Oreochromis mossambicus, the cancer risk (CR) values for Cr and As were significantly high, particularly for children, indicating a possible occurrence of acute health risk as it exceeded the threshold of 1 × 10-3 and suggesting a significant concern. Though consumption of fish on daily basis in such significant quantity is practically impossible both for adult and children, rendering these species safe.

Application of a new approach method to assess the hazard of complex legacy contaminated groundwater mixtures on fathead minnows in outdoor mesocosms.

Assessing the environmental risks of contaminated groundwater presents significant challenges due to its often-complex chemical composition and to dynamic processes affecting exposure of organisms in receiving surface waters. The objective of this study was to characterize the effects of groundwater collected from a legacy contaminated industrial site, in fish under environmentally relevant conditions. A 21-day fish short-term reproduction assay was conducted in outdoor wetland mesocosms by exposing adult fathead minnows (Pimephales promelas) to graded concentrations of groundwater (1 %, 3 %, and 6 %). Offspring were held in mesocosms up to four days post-hatch to apply a new approach method (NAM), the EcoToxChip™, to explore whether traditional apical endpoints could be predicted using an alternative mechanistic approach. None of the groundwater concentrations used in this study were lethal to fish. There was greater cumulative number of eggs produced at the highest concentration of exposure. However, no abnormal histological appearance was observed in the liver and gonads of fish and no significant effect was observed in the relative expression of genes, tubercle counts, and erythrocyte micronuclei counts compared to the negative control. Food availability in the mesocosms was also assessed and the abundance of zooplankton increased in all groundwater-treated mesocosms. Fathead minnow findings are in contrast to those obtained from previous controlled laboratory studies that revealed significant genotoxicity, hepatotoxicity, and reprotoxicity of the same mixtures. Several factors could explain these observations, including the aging of groundwater in mesocosms before fish addition resulting in photo- and biodegradation and binding to sediments of toxic components. Our static exposure scenario likely underestimated realistic exposure scenarios where groundwater inflow to surface water is generally semi-continuous. Nevertheless, focused transcriptome analysis using EcoToxChips also observed greater toxicity during previous laboratory tests compared to mesocosm scenarios, and thus, our results support the use of this NAM in the ecological risk assessment of contaminated groundwater.

Critical Evaluation and Meta-Analysis of Ecotoxicological Data on Per- and Polyfluoroalkyl Substances (PFAS) in Freshwater Species.

Despite the increasing concern regarding the ecological risks posed by per- and polyfluoroalkyl substances (PFAS), a lack of comprehensive understanding of their actual ecotoxicity remains. Through a meticulous examination of 91 peer-reviewed studies investigating effects at a population level and constructing probabilistic species sensitivity distributions (PSSDs), we present a state-of-the-science hazard assessment of PFAS in freshwater species. Using data subsets containing suboptimal data led to an overestimation of the predicted no-effect concentrations (PNECs) of PFAS. We report PNECs of perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonates (PFSAs) in freshwater to be 4.8-2000 µg/L and 0.4-8.9 µg/L, respectively, derived from high-quality data. Statistical analyses revealed that both functional groups and carbon chain length significantly influenced (p < 0.05) the variations in toxicity observed among different PFAS. This study underscores the importance of obtaining high-quality PFAS ecotoxicity data to comprehend associated hazards. The PNECs of PFAS derived in this study are higher compared to those of micro/nanoplastics and persistent organic pollutants. Our research offers valuable insights into prioritizing the regulation of more toxic PFAS.

Effects of changing spatial scale on debris-flow hazard assessment: A case study in the Dadu River basin, China.

Debris flows are a prevalent mountain hazard that poses severe risks to human life and property. Debris-flow hazard assessments at the regional scale are vital for risk management, which establish spatial associations between debris flows and their influencing factors based on specific evaluation units. Different spatial scales of evaluation units can influence the spatial attributes and associations obtained by statistics, and further affect the accuracy of hazard assessments. However, there is limited consensus regarding the optimal spatial scale of evaluation units for debris-flow hazard assessment. To address this issue, six different scales of grid cells and forty influencing factors related to topography, material sources, hydrology, and human activities are analyzed by the geographical detector model to assess the debris-flow hazards in the Dadu River basin, China. The results reveal that over 92 % of debris-flow points fall within hazardous zones across all spatial scales, confirming the effectiveness of the assessment model. Topography, particularly local gully topography, dominates the debris-flow occurrence in the study area, while human activities also significantly contribute. As the spatial scale of evaluation units increases, the explanatory power of the influencing factors improves, with the 90 % quantile ranging from 0.23 to 0.46. This result suggests that larger spatial scales weaken the spatial characteristics of the factors. The finer and more informative the factors are, the more sensitive to spatial scale effects. The 10 km × 10 km is identified as the optimal spatial scale, which effectively preserves the local spatial characteristics while avoiding information loss or overload. These findings provide valuable insights for enhancing the accuracy of hazard assessments and improving the efficiency of risk management.

Remote sensing identification and hazard assessment methods for spoil sites.

Spoil sites, as loose accumulations, are prone to instability after disturbances and are a serious threat to the safety of downstream communities. This research aims to rapidly and accurately assess the potential hazards of the numerous spoil sides. An integrated approach that combines spatial, aerial, and ground techniques was developed to rapidly identify and interpret the key factors influencing the stability of spoil sites. Subsequently, based on the results of numerical simulation of multiple combinations of unfavorable working conditions by the material point method, a hazard assessment methodology for spoil sites is proposed, which combines the limit equilibrium method with the improved hierarchical analysis. The proposed method is applied and validated on spoil sites along an expressway. The achieved results reveal that remote sensing combined with unmanned aerial vehicle (UAV) verification technology is capable of quickly and accurately identifying the critical elements of spoil sites. The hazard assessment of the spoil site is represented by the hazard coefficient (P), where 0 < P < 1 indicates safety, 1 ≤ P < 5 signifies instability, and P ≥ 5 represents extreme instability. The effectiveness of the proposed assessment approach is then verified through the on-site validation, which provides a vital reference for rapid identification and batch assessment of spoil sites.

A probabilistic hazard assessment for cyanobacterial toxins accounting for regional geography and water body trophic status.

Under climate change scenarios freshwater eutrophication is expected to increase, and with it the occurrence of cyanobacterial toxin-producing harmful algal blooms. In the current study, microcystin toxin occurrence data from literature sources and a long-term provincial monitoring program were used to conduct a probabilistic hazard assessment for Alberta, Canada. The large temporal and spatial range of data makes Alberta a model system for identifying regional geography and water body trophic status factors driving toxin concentrations. Environmental exposure distributions of microcystin concentrations were plotted and used to identify the likelihood of a given sample exceeding water guideline values as a function of regional geography, total phosphorus and chlorophyll-a concentration. This process identified regions with intensive cultivation and those most prone to water deficits associated with climate change to be most associated with exceedances of regulatory guideline values. Elevated phosphorus and chlorophyll-a concentrations were also drivers of toxin occurrence. This assessment can be used to identify water bodies of greatest risk to human and animal populations from cyanotoxins and thereby inform regulators as to most effective monitoring strategies.

Deep-sea mining rock-fragment dispersal scenarios associated with submesoscale forcings: A case study in the Atlantic.

In the last few years, the exploitation of deep-sea regions for minerals extraction raised international attention as an economically viable source for the mining industry. However, most of these minerals are found close to sensitive ecosystems that can be harmed by mining activities. Given the potential impact, there is a need for the establishment of best practices towards the adoption of preventive strategies for the sustainable management and exploitation of deep-sea environments. To accomplish this objective, numerical models have proven to be reliable tools to support decision-making. In the present study, a high-resolution eddy-resolving ocean numerical model was configured and integrated with a semi-Lagrangian model aiming to map the transport of rock-fragments associated with mining activities. The model was applied to an area rich in polymetallic sulphides at the Northern Mid-Atlantic Ridge (NMAR). Model results showed that local topography and circulation dynamics played an important role for the dispersion and settling of the rock-fragments. In the presence of local submesoscale processes, the residence time do not follow the neutral relation H/vs. It was demonstrated that, depending on the local hydrodynamics, rock-fragments released at sub-surface depth can impact wider areas, with a predicted impact on pelagic and benthic organisms.

Progression from in vivo validation to in vitro screening in hazard assessment for leukoderma-inducible chemicals.

Chemicals are representative environmental factors that affect human health. Recently, external exposure to a chemical of rhododenol (RD) caused chemical leukoderma, an acquired patchy hypopigmentation, in about 20,000 Asian people. The development of a hazard assessment system for accurate determination of leukoderma-inducible chemicals is required for the prevention of such tragedies. Case studies in humans have shown 6 chemicals, including RD, with a constitutive leukoderma-inducible potency and 3 chemicals with a photosensitive but not a constitutive leukoderma-inducible potency. In this study, the 6 positive and 3 negative control chemicals with or without constitutive leukoderma-inducible potencies were investigated by our previously developed in vivo hazard assessment system using tail skin of mice. Based on the results of validation, this study aimed to develop an in vitro hazard assessment system to correctly determine chemicals with a constitutive leukoderma-inducible potency. As expected, external exposure to the 6 positive control chemicals, but not external exposure to the 3 negative control chemicals, resulted in development of constitutive leukoderma in mouse tail skin with a decreased level of skin melanin and decreased number of melanocytes. Moreover, the 6 positive and 3 negative control chemicals were correctly distinguished by the presence or absence of endoplasmic reticulum (ER) stress induction, but not by tyrosinase-dependent cell death or production of reactive oxygen species (ROS), in immortalized normal melanocytes. The hazard assessment system using tail skin could be a solid in vivo tool to reliably determine the chemical potency of a chemical for constitutive leukoderma induction. The hazard assessment system focusing on ER stress induction in normal melanocytes might be a novel and convenient in vitro tool for accurately evaluating chemicals with leukoderma-inducible potencies. Thus, this study contributed to environmentology through the development of a screening system for preventing an environmental factor-related disease.

Natural radionuclide profiles and radiological risks in soils and rocks of the Koytash-Ugam Range, Uzbekistan.

This investigation quantifies the activity concentrations of natural radionuclides (226Ra, 232Th, and 40K) in the soils and certain rocks of the Koytash-Ugam Range, Uzbekistan, and assesses their radiological risks. Gamma-spectrometric analysis of soil and rock samples revealed activity concentrations ranging from 456.2 ± 56.0 to 813.9 ± 76.0 Bq kg-1 for 40K, 18.2 ± 6.3 to 70.0 ± 12.0 Bq kg-1 for 226Ra, and 30.1 ± 2.9 to 57.9 ± 10 Bq kg-1 for 232Th. This data indicates a heterogeneous distribution of radionuclides, informing radiation safety and health risk assessments on a global scale. The calculation of radiological hazard indices, including the alpha-index (ranging from 0.09 to 0.35), gamma-index (ranging from 0.40 to 0.73), and both internal (ranging from 0.40 to 0.54) and external (ranging from 0.36 to 0.54) hazard indices, was undertaken to ascertain potential health risks. The radium equivalent activity ranged from 108.4 to 199.3 Bq kg-1, and the absorbed dose rates were 51.0-93.3 nGy h-1 indoors and 96.6-178.2 nGy h-1 outdoors. These metrics underlie the estimated annual effective dose of 536.5-988.5 × 10-3 mSv y-1, highlighting the variability in radiation exposure. Additionally, the potential lifetime cancer risk was projected at 1770.4 to 3262.0 per million, with an annual gonadal dose equivalent of 361.9 to 655.5 µSv y-1, reflecting natural background radiation influence. The results underscore the importance of safe material use in construction and the necessity for routine natural radioactivity monitoring. Radon flux density (RFD) values within acceptable construction limits (26-176 mBq m-2 s-1) suggest the area's suitability for development, considering recommended safety guidelines. This study not only aids local environmental and public health frameworks but also enriches the international knowledge base, facilitating comparative studies for the advancement of global radiation protection standards. Through a detailed examination of radionuclide distribution in an under-researched area, our research highlights the critical need for integrated international approaches to natural radiological hazard assessment.

Assessing lethal and sublethal effects of pesticides on honey bees in a multifactorial context.

The registration of novel pesticides that are subsequently banned because of their unexpected negative effects on non-target species can have a huge environmental impact. Therefore, the pre-emptive evaluation of the potential effects of new compounds is essential. To this aim both lethal and sublethal effects should be assessed in a realistic scenario including the other stressors that can interact with pesticides. However, laboratory studies addressing such interactive effects are rare, while standardized laboratory-based protocols focus on lethal effects and not on sub-lethal effects. We propose to assess both lethal and sublethal effects in a multifactorial context including the other stressors affecting the non-target species. We tested this approach by studying the impact on honey bees of the insecticide sulfoxaflor in combination with a common parasite, a sub-optimal temperature and food deprivation. We studied the survival and the transcriptome of honey bees, to assess both the lethal and the potential sublethal effects of the insecticide, respectively. With this method we show that a field realistic concentration of sulfoxaflor in food does not affect the survival of honey bees; however, the significant impact on some key genes indicates that sublethal effects are possible in a realistically complex scenario. Moreover, our results demonstrate the feasibility and reliability of a novel approach to hazard assessment considering the interactive effects of pesticides. We anticipate our approach to be a starting point for a paradigm shift in toxicology: from an unifactorial, mortality-centered assessment to a multifactorial, comprehensive approach. This is something of the utmost importance to preserve pollination, thus contributing to the sustainability of our food production system.

Dynamic evolution characteristics and hazard assessment of compound drought/waterlogging and low temperature events for maize.

Hazard assessment is fundamental in the field of disaster risk management. With the increase in global warming, compound water and temperature events have become more frequent. Current research lacks risk assessments of low temperatures and their compound events, necessitating relevant hazard assessment work to improve the accuracy and diversity of maize disaster prevention and mitigation strategies. This study comparatively analyzed the dynamic evolution characteristics and hazards of compound drought/waterlogging and low temperature events (CDLEs and CWLEs) for maize in the Songliao Plain during different growth periods from 1981 to 2020. First, composite drought/waterlogging and low temperature magnitude indices (CDLMI and CWLMI) were constructed to quantify the intensity of CDLEs and CWLEs by fitting non-exceedance probabilities. Next, static and dynamic hazard assessment models were developed by fitting probability density and cumulative probability density curves to CDLMI and CWLMI. The results showed that the correlations between SPRI and LTI across different decades were mainly negative during the three growth periods. The hazard ratings for both CDLEs and CWLEs were relatively high in the northern part of the study area, consistent with the higher occurrence, duration, and severity of both CDLEs and CWLEs at higher latitudes. Relative to 2001-2010, the center of gravity of hazard shifted southward for CDLEs and northward for CWLEs in 2011-2020. The mean duration, frequency, and hazard were generally higher for CWLEs, but CDLEs were associated with more severe maize yield reductions. This study provides new insights into compound disaster risk assessment, and the research methodology can be generalized to other agricultural growing areas to promote sustainable development of agricultural systems and food security.

Ions and nanoparticles of Ag and/or Cd metals in a model aquatic microcosm: Effects on the abundance, diversity and functionality of the sediment bacteriome.

Metals can be adsorbed on particulate matter, settle in sediments and cause alterations in aquatic environments. This study assesses the effect of Ag and/or Cd, both in ionic and nanoparticle (NP) forms, on the microbiome of sediments. For that purpose, aquatic controlled-microcosm experiments were exposed to an environmentally relevant and at tenfold higher doses of each form of the metals. Changes in the bacteriome were inferred by 16S rDNA sequencing. Ionic Ag caused a significant decrease of several bacterial families, whereas the effect was opposite when mixed with Cd, e.g., Desulfuromonadaceae family; in both cases, the bacteriome functionalities were greatly affected, particularly the nitrogen and sulfur metabolism. Compared to ionic forms, metallic NPs produced hardly any change in the abundance of microbial families, although the α-biodiversity of the bacteriome was reduced, and the functionality altered, when exposed to the NPs´ mixture. Our goal is to understand how metals, in different forms and combinations, released into the environment may endanger the health of aquatic ecosystems. This work may help to understand how aquatic metal pollution alters the structure and functionality of the microbiome and biogeochemical cycles, and how these changes can be addressed.

Chemical hazard assessment toward safer electrolytes for lithium-ion batteries.

Commercialization of rechargeable lithium-ion (Li-ion) batteries has revolutionized the design of portable electronic devices and is facilitating the current transition to electric vehicles. The technological specifications of Li-ion batteries continue to evolve through the introduction of various high-risk liquid electrolyte chemicals, yet critical evaluation of the physical, environmental, and human health hazards of these substances is lacking. Using the GreenScreen for Safer Chemicals approach, we conducted a chemical hazard assessment (CHA) of 103 electrolyte chemicals categorized into seven chemical groups: salts, carbonates, esters, ethers, sulfoxides-sulfites-sulfones, overcharge protection additives, and flame-retardant additives. To minimize data gaps, we focused on six toxicity and hazard data sources, including three empirical and three nonempirical predictive data sources. Furthermore, we investigated the structural similarities among selected electrolyte chemicals using the ChemMine tool and the simplified molecular input line entry system inputs from PubChem to evaluate whether chemicals with similar structures exhibit similar toxicity. The results demonstrate that salts, overcharge protection additives, and flame-retardant additives contain the most toxic components in the electrolyte solutions. Furthermore, carbonates, esters, and ethers account for most flammability hazards in Li-ion batteries. This study supports the complementary use of quantitative structure-activity relationship models to minimize data gaps and inconsistencies in CHA. Integr Environ Assess Manag 2024;00:1-14. © 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Scientometric review on multiple climate-related hazards indices.

As the spectre of climate change looms large, there is an increasing imperative to develop comprehensive risk assessment tools. The purpose of this work is to evaluate the evolution and current state of research on multi-hazard indices associated with climate-related hazards, highlighting their crucial role in effective risk assessment amidst the growing challenges of climate change. A notable gap in cross-regional comparative studies persists, presenting an opportunity for future research to enhance global understanding and foster universal resilience strategies. However, a significant surge in research output is apparent, following key global milestones related to climate change action. The research landscape is shown to be highly responsive to international policy developments, increasingly adopting interdisciplinary approaches that integrate physical, social, and technological dimensions. Findings reveal a robust emphasis on geospatial analysis and the development of various indices that transform abstract climate risks into actionable data, underscoring a trend towards localized, context-specific vulnerability assessments. Based on dataset systematically curated under the PRISMA guidelines, the review explores how prevailing research themes are reflected in influential journals and author networks, mapping out a dynamic and expanding academic community. Moreover, this work provides critical insights into the underlying literature by conducting a thematic analysis on the typology of studies, the focus on coastal areas, the inclusion of climate change scenarios, the geographical coverage, and the types of climate-related hazards. The practical implications of this review are profound, providing policymakers and practitioners with meaningful insights to enhance climate change mitigation and adaptation efforts through the application of index-based methodologies. By charting a course for future scholarly endeavours, this article aims to strengthen the scientific foundations supporting resilient and adaptive strategies for regions worldwide facing the multifaceted impacts of climate change.

Grouping of short alkyl-chain branched carboxylic acids for developmental toxicity.

Read-across (RAx) and grouping of chemicals into categories are well-known concepts in toxicology. Recently, ECHA proposed a grouping approach for branched-chain carboxylic acids (BCAs) including more than 60 branched-chain saturated carboxylic acids for hazard identification. Grouping was based only on structural considerations. Due to developmental effects of two members, ECHA postulated that "all short carbon chain acids … are likely reproductive and developmental toxicants". This work analyzes available data for BCAs. The number of compounds in the group can be significantly reduced by eliminating metal and organic salts of BCAs, compounds of unknown or variable composition, and complex reaction products or biological materials (UVCB compounds). For the resulting reduced number of compounds, grouping is supported by similar physicochemical data and expected similar biotransformation. However, analysis of adverse effects for compounds in the group and mechanistic information show that BCAs, as a class, do not cause developmental effects in rats. Rather, developmental toxicity is limited to selected BCAs with specific structures that share a common mode of action (histone deacetylase inhibition). Thus, the proposed grouping is unreasonably wide and the more detailed analyses show that structural similarity alone is not sufficient for grouping branched-chain carboxylic acids for developmental toxicity.

Assessing systemic, developmental, and reproductive toxicity and estrogenicity of Korean red ginseng extract G1899 in juvenile Sprague-Dawley Rats.

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats. Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines. Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity. Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day.