[2-(2-methoxymethylethoxy)methylethoxy]propanol (tripropylene glycol monomethyl ether, TPGME, CAS No. 25498-49-1) is a type of glycol ether coupling solvent used in diverse industrial applications. TPGME has recently been targeted for screening assessment under the Japanese Chemical Substances Control Law (CSCL); however, public data on its repeated-dose toxicity are limited. Therefore, a combined repeated-dose and reproductive/developmental toxicity study was performed to assess toxicity of TPGME and to fill these data gaps. Male and female Crl:CD(SD) rats were orally administered TPGME at doses of 0, 100, 300, or 1,000 mg/kg/day. No toxicologically significant changes were observed at doses up to 300 mg/kg/day in both sexes. At 1,000 mg/kg/day, females showed clinical signs of neurotoxicity, such as staggering gait, decreased spontaneous locomotor activity, and reduced grip strength, while males exhibited a downward trend in grip strength, decreased serum T₄ levels, and α2u-globulin nephropathy. Both sexes showed increased liver weights at this dose. The changes in serum T₄ levels were reversible with no corresponding thyroid or liver histopathology. Furthermore, the α2u-globulin nephropathy was rat-specific and deemed irrelevant to human health risk. Given the lack of associated histopathological changes, the increased liver weights were considered adaptive changes. Therefore, these findings of general toxicity were collectively deemed non-adverse. On the other hand, no reproductive or developmental toxicity was observed at any dose tested up to 1,000 mg/kg/day. Based on these findings, the no-observed-adverse-effect level for repeated-dose toxicity was determined at 300 mg/kg/day for both sexes, while that for reproductive and developmental toxicity was at ≥ 1,000 mg/kg/day.

Cis3-hexenyl salicylate (HS) is a fragrance ingredient and specified as an existing substance, which was on the market before the Chemical Substance Control Law (CSCL) was established in Japan. Because the toxicity of HS was unknown, the combined repeated dose toxicity study with the reproductive/developmental toxicity screening test of HS was conducted according to the organization for economic co-operation and development (OECD) TG 422 for screening assessment under the CSCL. Male and female rats were administered HS at 0 (control: corn oil), 40, 120, and 360 mg/kg bw/day for 42 and 41–49 days, respectively. Deaths were observed in three dams on the day of delivery or after delivery at 360 mg/kg bw/day. HS exerted hematological effects indicating anemia or weakened blood clotting at 360 mg/kg bw/day in both sexes, which might be related to the dams’ death. HS may be hydrolyzed as salicylic acid, a known prostaglandin synthesis inhibitor, and cis-3-hexenol. Oral dosing of HS at 360 mg/kg bw/day exerted toxicological effects probably mediated by decreased prostaglandin levels, which included weakened blood clotting, indicative kidney injury, glandular stomach erosion, increased trabecular bone formation in the femoral bone, and prolonged gestation length. HS also exerted adverse effects on reproduction at 360 mg/kg bw/day, decreasing the gestation index and number of liveborns. Moreover, delivered pups exhibited decreased body weights on postnatal days 0 and 4 and malformations such as exencephaly and spinal rachischisis at the same dose. Therefore, the no-observed-adverse-effect level was determined as 120 mg/kg bw/day for both repeated dose general toxicity and reproductive/developmental toxicity.

To clarify the extent of seawater pollution by human waste in Tokyo Bay, pharmaceutical concentrations were analyzed using LC-MS/MS, and antimicrobial activity was assayed using the disk diffusion method. Four pharmaceuticals, diphenhydramine, clarithromycin, carbamazepine, and bezafibrate, were detected in Tokyo Bay seawater. Their concentrations were low near the bay mouth and increased toward the Tokyo waterfront. At Kasai Marine Park, a registered wetland under the Ramsar Convention for the protection of wild bird habitats located along the Tokyo waterfront, the maximum concentration of clarithromycin (72.4 ng/L) exceeded the predicted no-effect concentration (69 ng/L), indicating potential ecological risks. Meanwhile, at Odaiba Marine Park, a beach used for bathing and water sports, also situated along the Tokyo waterfront, the mean concentrations of the four pharmaceuticals in seawater were higher than those at Kasai Marine Park; however, none were considered to pose a risk to human health. Furthermore, antimicrobial activity was detected in seawater extracts collected from both parks. This activity cannot be explained solely by clarithromycin, the most frequently prescribed antibiotic, suggesting the involvement of multiple antimicrobial substances. To prevent adverse ecological effects of pharmaceutical contamination in seawater, it is necessary not only to decompose pharmaceuticals in sewage treatment plants but also to refrain from using unnecessary pharmaceuticals and to dispose of them through sewer systems.

Cisplatin is a widely used chemotherapeutic agent; however, its clinical utility is limited by dose-dependent nephrotoxicity. Although hydration and diuretics are commonly employed to mitigate renal injury, their protective efficacy remains suboptimal. Correspondingly, Eucommia ulmoides Oliv. leaf extract (ELE) is a functional food ingredient with diuretic, antioxidant, and anti-inflammatory properties. Therefore, this study investigated the protective effects of ELE against cisplatin-induced nephrotoxicity (CIN) in mice and elucidated the underlying mechanisms. Mice were administered cisplatin (15 mg/kg) with or without ELE or furosemide (potent diuretic). Cisplatin administration markedly elevated blood plasma urea nitrogen levels and reduced creatinine clearance, thereby indicating renal dysfunction. Co-administration of ELE substantially ameliorated renal function markers and attenuated histological tubular damage. In contrast, furosemide failed to improve renal dysfunction despite increasing urine output. This suggests that diuresis alone is insufficient for renal protection. Furthermore, ELE markedly suppressed cisplatin-induced upregulation of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and renal injury markers (kidney injury molecule-1 and lipocalin-2) in kidney tissues. These findings indicate that ELE exerts renoprotective effects against CIN through diuretic, anti-inflammatory, and antioxidant mechanisms. These mechanisms most likely involve modulation of inflammatory signaling pathways in the kidneys. Overall, ELE shows promising potential as an adjunctive therapeutic agent for patients undergoing chemotherapy.