Fundamental Toxicological Sciences

2021 - Vol. 8 No. 4

2021 - Vol. 8

Original Article
Safety evaluation of 2-aza-8-oxohypoxanthine by in vitro skin sensitization and human tests Vol.8, No.4, p.123-133
Hisae Aoshima , Takunori Matsumoto , Rinta Ibuki , Hirokazu Kawagishi
Released: September 10, 2021
Abstract Full Text PDF[1M]

2-Azahypoxanthine (AHX) is a compound isolated from the agaricomycete Lepista sordida that forms fairy rings and 2-aza-8-oxohypoxanthine (AOH) is a metabolite of AHX in plants. In the present study, we assessed the safety of AOH for cosmetic applications via in vitro skin sensitization tests and human skin sensitization, phototoxicity, and photosensitization assays. In the tests, AOH did not induce skin sensitization in both human cell line activation test (h-CLAT) and KeratinoSensTM methods. AOH also did not induce human dermal phototoxicity or photosensitivity. Moreover, in repeat insult patch tests, the compound did not induce any human skin reaction. Hence, we conclude that AOH is safe as a cosmetic ingredient. To the best of our knowledge, this investigation is the first to evaluate the safety of AOH on human skin.

Original Article
Health risk assessment on mercury, cadmium and lead in marketed cigarettes Vol.8, No.4, p.117-122
Quang Phan Dinh , Sylvester Addai-Arhin , Randy Novirsa , Huiho Jeong1 , Willy Cahya Nugraha , Pham Hung Viet , Nobuaki Tominaga , Yasuhiro Ishibashi , Koji Arizono
Released: September 08, 2021
Abstract Full Text PDF[758K]

The Hg, Cd, and Pb concentrations in marketed cigarettes from South Korea, Vietnam, Japan, Indonesia, Taiwan, Thailand, United Kingdom (UK), Belgium, Italy, Finland, and France were investigated. The average Hg concentration in cigarettes marketed in Vietnam and Thailand had the highest trend. Meanwhile, there was more Cd found in cigarettes from Thailand, UK, and Belgium. The Pb concentrations in cigarettes from Belgium, UK, and Korea were higher than in others. In the health risk assessment in this study, the significant non-carcinogenic health risk (HI) values of Hg, Cd, and Pb were investigated. The results showed that the HI of Hg, Cd, and Pb were 4.12 × 10−2, 4.07 × 101, and 9.78 × 100, respectively. It indicated that only Cd and Pb had a significant HI. When the incremental lifetime cancer risk (ILCR) was estimated, the ILCRs for both Cd (7.32 × 10−4) and Pb (0.88 × 10−5) in cigarettes were higher than the acceptable limit. The acceptable and significant cancer risks for Pb and Cd, respectively were evaluated in cigarettes used in this study.

Original Article
Repeated-dose and reproductive/developmental toxicity screening of polyoxymethylene in rats Vol.8, No.4, p.103-116
Mariko Matsumoto , Sakiko Fujii , Nozomu Hirose , Takako Iso , Yoshiyuki Shigeta , Yasumasa Murata , Kaoru Inoue , Akihiko Hirose
Released: August 27, 2021
Abstract Full Text PDF[902K]

>The Japanese government requires risk assessment of chemicals under the Chemical Substances Control Law (CSCL). Toxicity data for polyoxymethylene (paraformaldehyde; CAS No.: 30525-89-4) for human health are insufficient though the chemical needs a screening assessment under the CSCL. Thus, polyoxymethylene was selected by the Safety Examination of Existing Chemicals and Safety Programmes of the Ministry of Health, Labour and Welfare (MHLW) to assess repeated-dose and reproductive/developmental toxicity. A combined toxicity screening was conducted following the OECD TG422. Male and female rats were administered the test chemical once daily by gavage at doses of 0 (control), 20, 60, or 200 mg/kg bw from 14 days before mating for a total of 28 to 61 days. The 200 mg/kg bw/day dose caused a significant decrease in food consumption. Histopathological examination found ulcers in the forestomach and glandular stomach, and erosion and inflammatory cell infiltration in the submucosa of the glandular stomach at the end of dosing in both sexes. Inflammatory cell infiltration in the submucosa of the glandular stomach was also observed in both sexes after the recovery period. No reproductive and developmental toxicity was observed even at the highest dose. A no-observed-adverse-effect level (NOAEL) for repeated-dose toxicity was 60 mg/kg bw/day, and a NOAEL for reproductive and developmental toxicity was 200 mg/kg bw/day, the highest dose tested.

Antidiabetic agent did not impair spermatogenesis in spontaneously hyperglycemic and diabetic rats Vol.8, No.4, p.97-101
Taiki Kobayashi , Takasumi Shimomoto , Junichi Namekawa , Masanobu Kanou , Hirotsugu Kato , Seishiro Sakamoto , Takeshi Iijima , Hideharu Ochiai
Released: August 02, 2021
Abstract Full Text PDF[849K]

In previous studies, we suggested that hypoglycemia induced by antidiabetic drugs causes testicular toxicity. In this study, we evaluated whether spontaneously hyperglycemic and diabetic rats (Goto-Kakizaki rats) treated with an antidiabetic drug showed testicular histopathological changes. TMG-123, a glucokinase activator, was given to the rats for 4 weeks at 12.5, 25 and 50 mg/kg. The exposures of TMG-123 at 50 mg/kg were similar to those that caused hypoglycemia and testicular toxicity in SD rats, and the decrease in blood glucose levels on day 28 of dosing was similar to that in SD rats, which showed that the pharmacological action of TMG-123 was similar in both SD and Goto-Kakizaki rats. However, blood glucose levels in Goto-Kakizaki rats were originally much higher than those in SD rats, and hypoglycemia was not induced in the Goto-Kakizaki rats. The histopathological evaluation showed no testicular changes. These results corroborate our hypothesis.