In the European Union, a revised version of the “Guideline on Environmental Risk Assessment of Medicinal Products for Human Use” (EMEA/CHMP/SWP/4447/00) came into effect in September, 2024. This review explains the revised contents of the Guideline, summarizes points to note when conducting an environmental risk assessment, and proposes a useful project model for the pharmaceutical industry.

Sediments constitute the benthic environment, and play an important role in marine ecosystems. Various chemicals persist in sediments and can affect the benthic organisms. However, it has generally been difficult to identify specific toxicants that critically the effects in organisms. In the present study, we evaluated the toxicities of sediments collected from several sites in Japanese coastal areas, using fish embryos. As a result, some sediments induced embryo mortality and malformation in hatching larvae. We explored several approaches to facilitate the identification of causative chemicals based on biological responses in fish embryos. Hydrophobic extracts added into test water obtained from most sediments induced effects such as mortality and malformations in embryos. However, because hydrophilic extracts also affected embryos for a few sites, we could not distinguish the remarkable signatures based solely on the extract exposures. In addition, receptor activation by ligand-binding chemicals derived from these extracts―implicating xenobiotic metabolism, vitamin metabolism, and other pathways―was examined using the corresponding nuclear receptor target genes, and some genes changed at least partially with their effect-related factors. The approach of obtaining extracts followed by gene analysis, owing to its broad applicability, was suggested to be a potentially effective method for picking up candidate causative toxicants in sediments in the future.

Amine-based compounds, such as synthetic polyethyleneimines (PEIs) and biogenic polyamines, are promising CO₂ capture materials because of their high affinity for acidic gases. However, their potential toxicity in aquatic environments remains a concern. In this study, we compared the toxicity of three polyamines (putrescine, spermidine, and spermine) and of PEIs with average molecular masses ranging from 300 to 100,000 at concentrations of 1–1,000 ppm. Toxicity assays were conducted using planula larvae of a diploblastic species, the stony coral Acropora digitifera, and juvenile triploblasts, including zebrafish (Danio rerio), the Japanese big-eared Radix freshwater snail (Radix auricularia japonica), and embryos of the collector urchin (Tripneustes gratilla). Coral larvae exhibited high sensitivity to biogenic polyamines with a median lethal concentration (LC₅₀) of 22.2 ppm for putrescine, but relatively low sensitivity to PEIs (LC₅₀: 227.6–>1,000 ppm). In contrast, triploblastic animals were highly sensitive to PEIs (LC₅₀: 0.3–3.2 ppm), while being less sensitive to biogenic polyamines (LC₅₀: 294.9–389.7 ppm for putrescine) except for spermine. Notably, some PEIs exhibit toxicity even at concentrations below 1 ppm. These findings emphasize the importance of conducting organism-specific environmental toxicity risk assessments when amine-based CO₂ capture materials are used, particularly to avoid adverse effects on aquatic ecosystems.

We review the current challenges in the ecological risk assessment of ethylenediaminetetraacetic acid (EDTA) and cationic surfactants under Japan’s Chemical Substances Control Law. The complexity of EDTA toxicity assessment arises from its chelating properties, which influence metal bioavailability and ecological toxicity, making conventional assessment methods inadequate. Meanwhile, the toxicity of cationic surfactants is significantly affected by environmental factors, particularly organic matter content and water quality parameters. These variations pose substantial difficulties in achieving reliable toxicity assessments. While the Biotic Ligand Model (BLM) has been applied to address similar challenges in metal toxicity assessment, its effectiveness in evaluating EDTA and cationic surfactants has yet to be fully demonstrated. This paper examines existing evaluation methods, identifies their limitations, and proposes potential approaches for improving the reliability of risk assessments for these difficult-to-test substances.