The compound 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a replacement for perfluorooctanesulfonate (PFOS) in the electroplating industry, has been widely detected in numerous environmental matrices, human sera, and organisms. Due to regulations that limit PFOS use, F-53B use is expected to increase. Therefore, in this study, we performed a subchronic oral toxicity study of F-53B in Sprague Dawley (SD) rats. F-53B was administered orally once daily to male and female rats for 28 days at doses of 5, 20, and 100 mg/kg/day. There were no toxicologically significant changes in F-53B-treated rats, except in the thyroid gland. However, F-53B slightly reduced the serum concentrations of thyroid hormones, including triiodothyronine and thyroxine, compared with their concentrations in the vehicle group. F-53B also induced follicular hyperplasia and was associated with increased thyroid hormone biosynthesis-associated protein expression. These results demonstrate that F-53B is a strong regulator of thyroid hormones in SD rats as it disrupts thyroid function. Thus, caution should be exercised in the industrial application of F-53B as an alternative for PFOS.

Graphene nanoplatelets (GNPs) are one of the major types of carbon based nanomaterials that have different industrial and biomedical applications. There is a risk of exposure to GNP material in individuals involved in their large-scale production and in individuals who use products containing GNPs. Determining the exact toxicity of GNP nanomaterials is a very important agenda. This research aimed to evaluate the skin sensitization potentials induced by GNPs using two types of alternative to animal testing. We analyzed the physicochemical characteristics of the test material by selecting a graphene nanomaterial with a nano-size on one side. Thereafter, we evaluated the skin sensitization effect using an in vitro and an in vivo alternative test method, respectively. As a result, we found that GNPs do not induce skin sensitization. In addition, it was observed that the administration of GNPs did not induce cytotoxicity and skin toxicity. This is the first report of skin sensitization as a result of GNPs obtained using alternative test methods. These results suggest that GNP materials do not cause skin sensitization, and these assays may be useful in evaluating the skin sensitization of some nanomaterials.

This study was conducted to provide evidence, using in vitro and in silico testing methods, regarding the adverse effects of iprodione, a representative dichlorophenyl dicarboxamide fungicide, on the endocrine system. In the present study, we used the HeLa9903 stably transfected transactivation assay (OECD TG 455), 22Rv1/MMTV_GR‒KO androgen receptor transcriptional activation assay (OECD TG 458), and toxicity prediction using VEGA QSAR. Our results showed that iprodione had no estrogen receptor antagonistic or androgen receptor agonistic effects; however, iprodione was determined to be an estrogen receptor agonist (log PC₁₀ value is less than − 9) and androgen receptor antagonist (log IC₃₀ value is − 4.58) without intrinsic toxicity against the human cell lines used in this study. VEGA QSAR was used to evaluate five substances with structures similar to that of iprodione. Among them, four chemicals were found to have positive androgen receptor and aromatase activities and have been observed to be developmental toxicants. These results suggest that iprodione regulates steroid hormone receptor interactions and is a potential reproductive toxicant.

Sub-chronic toxicity studies using rats have been conducted for Cynanchum wilfordii (Maxim.) Hemsley (CW) and Cynanchum auriculatum Royle ex Wight (CA). CW water extract didn’t show any adverse effects whereas administering CW powder decreased body weights in complication with decreased food consumptions. In the case of CA water extract, triglyceride and absolute/relative liver weights were elevated and vacuolation was observed in liver. Treated CA powder in male rats increased alanine aminotransferase and aspartate aminotransferase and induced single cell necrosis and multinucleated hepatocyte in liver. As for female rats, increased absolute/relative weights and hypertrophy/vacuolation in adrenal glands and vacuolation in ovaries were observed when administered CA powder. In conclusion, no observed adverse effect level (NOAEL) of CW water extract was over 5000 mg/kg/day, while NOAEL of CW powder was 700 mg/kg/day for female and 150 mg/kg/day for male. In case of CA, NOAEL of water extract was 1500 mg/kg/day for male and 2000 mg/kg/day for female, while NOAEL of powder was 150 mg/kg/day for both gender. To the best of our knowledge, this is the first sub-chronic toxicity study on the adverse effects, target organs and its dose levels of C. wilfordii (Maxim.) Hemsley and C. auriculatum Royle ex Wight following GLP protocols.

The skin sensitization potential of agrochemicals can be assessed using laboratory methods such as the keratinocyte activation assay so that their use in regulatory toxicology might replace experimental animal testing. Here, we evaluated the skin sensitization potential of 11 agrochemicals by using an antioxidant response element–nuclear factor erythroid 2 luciferase assay in KeratinoSens and LuSens cells and applying a skin sensitization adverse outcome pathway (AOP). The KeratinoSens and LuSens assays consistently evaluated the skin sensitization potential of 10/11 agrochemicals with reference to animal testing databases. Benomyl, pretilachlor, fluazinam, terbufos, butachlor, and carbosulfan were correctly detected as sensitizers, and glufosinate ammonium, oxiadiazon, tebuconazole, and etofenprox were correctly detected as non-sensitizers. For diazinon, the skin sensitizing potential was positive in the KeratinoSens assay but not in the LuSens assay. These results suggest that the evaluation of in vitro skin sensitization using the AOP mechanism can be applied to assess active agrochemicals.