Initial hazard assessment of ethyl(dimethyl)(tetradecyl)ammonium ethyl sulfate: Genotoxicity tests and combined repeated-dose and reproductive/developmental toxicity screening in rats.

Ethyl(dimethyl)(tetradecyl)ammonium ethyl sulfate, used in laundry detergents, shampoos, and body soaps, is classified by the Japanese Chemical Substances Control Law as a priority assessment chemical substance for environmental effects. However, its toxicity data for human health are insufficient. This study evaluated this chemical under the Safety Examination of Existing Chemicals and Safety Programmes of the Ministry of Health, Labour and Welfare (MHLW). The MHLW conducted bacterial reverse mutation (Ames test), in vitro chromosomal aberration, and combined repeated-dose and reproductive/developmental toxicity screening tests. We performed a screening assessment of ethyl(dimethyl)(tetradecyl)ammonium ethyl sulfate for human health. The chemical showed a negative reaction in the Ames test and a positive reaction in the in vitro chromosomal aberration test with metabolic activation in rats. The combined repeated-dose and reproductive/developmental toxicity screening test showed significantly decreased food consumption at 50 mg/kg body weight/day, but no reproductive and developmental toxicity was observed. The no-observed-effect level of 15 mg/kg/day was obtained as a screening value. Therefore, this chemical was classified as hazard class 3, with a derived-no-effect level of 0.025 mg/kg/day. The results of this study will be useful for risk assessment of groups of structurally similar alkyl quaternary ammonium surfactants.

Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats.

1,4-Dichlorobutane (1,4-DCB) is used as raw materials for drugs, pesticides, fragrances, and chemical fibers, and being used as a solvent. Its toxicity data was insufficient for screening assessment under the Japanese Chemical Substances Control Law. We conducted toxicity tests and hazard classification for screening assessment 1,4-DCB showed negative in the Ames test, positive in the in vitro chromosomal aberrations test with metabolic activation, and negative in the in vivo mouse bone-marrow micronucleus test. The 28-day repeated-dose toxicity study, where male and female rats were administered 1,4-DCB by gavage at 0, 12, 60, and 300 mg/kg/day, showed significant effects on the liver and pancreas from 12 mg/kg/day and kidney at 300 mg/kg/day. Based on periportal hepatocellular hypertrophy and decreased zymogen granules in pancreas, the lowest observed adverse effect level (LOAEL) of 12 mg/kg/day was obtained. The reproductive/developmental toxicity screening study, in which male and female rats were administered 1,4-DCB by gavage at dose of 0, 2.4, 12, and 60 mg/kg/day for 42-46 days, showed that the delivery index was decreased at 60 mg/kg/day without maternal toxicity. Based on the general toxicity, we classified this chemical as hazard class 2, with a D-value (Derived No Effect Level) of 0.002 mg/kg/day.

HYGIENIC SUBSTANTIATION OF NECESSITY FOR MONITORING IN THE ENVIRONMENTAL OBJECTS OF SDHI FUNGICIDES CONSIDERING THEIR POSSIBLE IMPACT ON THE THYROID GLAND.

OBJECTIVE: The aim: Was hygienic substantiation of necessity for monitoring in the environmental objects of SDHI fungicides considering their possible impact on the thyroid gland. PATIENTS AND METHODS: Materials and methods: To test the proposed selection criteria for hygienic monitoring of pesticides that affect the thyroid gland, we evaluated 4 new SDHI fungicides from the chemical class of pyrazolecarboxamides (isopyrazam, pentiopyrad, sedaxan, fluxapyroxad). RESULTS: Results: Based on the results obtained, all studied compounds are assigned to the second pesticide group, hygienic monitoring of which is desirable but not required. This is due, on the one hand, to their low toxicity, to the other, to low environmental sustainability. CONCLUSION: Conclusions: It was shown, that compared to other classes of pesticides, the studied are much less dangerous in terms of groundwater contamination.

[Peroral toxicological assessment of bentonite nanoclay used in the food industry].

Bentonite nanoclay (NC) manufactured from the natural sedimentary mineral bentonite contains more than 90% montmorillonite. Currently, it is widely used in food industry as processed aids - adsorbents for the purification of vegetable oils and beverages. Clay minerals have also applications as food additives and components in composite package materials. In vitro studies have shown that various forms of NC exerted cytotoxicity in many cell lines, whereas in vivo evidence of NC oral toxicity is contradictory. Therefore, this study aimed to assess the acute oral toxicity of NC and to evaluate its toxicological characteristics in a subacute 92-day experiment on Wistar rats with a daily oral administration in doses of 1, 10, and 100 mg/kg body weight (bw). Material and methods. The NC acute toxicity was evaluated in 8 male and 8 female rats with the initial bw 236±10 and 203± 10 g, respectively. NC was administered as an aqueous dispersion intragastrically at a dose of 5 g/kg bw. On the 14th day (end of the experiment), an autopsy of the chest and abdominal organs was performed. The subacute experiment was carried out on 64 male rats with an average initial bw of 117±7 g. During the experiment the levels of anxiety and memory function were evaluated using the test "Conditional reflex of passive avoidance". On the 90th day of the experiment, diurnal urinary excretion of creatinine and selenium was evaluated. At the end of the experiment, the integral parameters, the state of the intestinal wall permeability were assessed. Hematological and biochemical parameters were examined in blood, the content of non-protein thiols and the number of cells in apoptosis were determined in liver, and the state of cultivated microbiome populations was studied in cecum. Results. The results of the determination of NC acute toxicity showed the absence of rat's mortality and specific pathological changes in the internal organs at a dose as large as 5000 mg/kg bw, which allowed attributing NC to the V hazard class. Nevertheless, under the conditions of the 92-day experiment, NC caused some adverse biological effects on rat's organism. So, even at an NC dose of 1 mg/kg bw, there was a sharp inhibition of the symbiotic bifidobacterium growth, an increase in platelet count, in LDL and the LDL/HDL ratio, together with the presence of hypertriglyceridemia. At a dose of 10 mg/kg bw, an increase in spleen mass and a decrease in the de Ritis coefficient (AsAT/AlAT) were established. At a dose of 100 mg/kg bw there were shifts in the leukocyte blood count, an excessive enterococci growth in the cecum, significantly increased animal bw, along with the decrease of AsAT/AlAT and the level of serum nitrogen metabolites, indirectly indicating inhibition of catabolic processes. However, at the highest dose of NC, intestinal absorption of the protein antigen - ovalbumin, was apparently completely blocked. Conclusion. The data obtained have shown that NC has potentially adverse effects on the rats mainly at a dose of 100 mg/kg bw, nevertheless, its NOAEL in the 92-day daily oral exposure experiment is probably less than 1 mg/kg bw.

Initial hazard assessment of 4-benzylphenol, a structural analog of bisphenol F: Genotoxicity tests in vitro and a 28-day repeated-dose toxicity study in rats.

4-Benzylphenol (CAS No. 101-53-1), a structural analog of bisphenol F, has estrogenic activity in vitro and in vivo, as is the case with bisphenol F. 4-Benzylphenol is used in plastics and during organic synthesis. Since its safety is largely unknown, we conducted toxicity tests as part of screening risk assessment in an existing chemical safety survey program. Based on results of the Ames test and the chromosomal aberration test using Chinese hamster lung cells (OECD TG 471 and 473), 4-benzylphenol was determined to be non-genotoxic in vitro. In a 28-day repeated-dose toxicity study, Crl:CD (SD) rats were administrated 4-benzylphenol by gavage at 0, 30, 150, or 750 mg/kg/day (OECD TG 407). Consequently, body weight was lower in males at 750 mg/kg/day. In the liver, relative organ weights were increased in both sexes at 750 mg/kg/day, and centrilobular hepatocellular hypertrophy was observed in males at 150 and 750 mg/kg/day. In the forestomach, hyperkeratosis and hyperplasia of squamous cells were observed in males at 150 and 750 mg/kg/day, and in females at 750 mg/kg/day. Based on these results, we identified the NOAEL for 4-benzylphenol as 30 mg/kg/day, with a hazard assessment value (D-value) of 0.05 mg/kg/day corresponding to hazard class 3.

Initial hazard assessment of benzyl salicylate: In vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats.

Benzyl salicylate is used as a fragrance ingredient and an ultraviolet light absorber, but its toxicity is unknown. Therefore, toxicity tests and hazard classification were conducted for screening assessment under the Japanese Chemical Substances Control Law. Benzyl salicylate was found to be non-genotoxic in vitro based on the chromosomal aberration test using Chinese hamster lung cells. However, the combined repeated-dose and reproductive/developmental screening toxicity test, in which male and female rats were administered benzyl salicylate by gavage at 0, 30, 100, or 300 mg/kg/day for 42 and 41-46 days, respectively, from 14 days before mating until postnatal Day 4, showed that repeated doses had major effects on the thymus, liver, epididymis, and femur at 100 and/or 300 mg/kg/day. Furthermore, although benzyl salicylate had no effect on the estrus cycle, fertility, corpus lutea, or implantation rate, embryonic resorption, offspring mortality, and neural tube defects were observed at 300 mg/kg/day, and the offspring had lower body weights at 30 and 100 mg/kg/day, suggesting teratogenicity similar to other salicylates. Based on the developmental toxicity, this chemical was classified as hazard class 2, with a lowest observed adverse effect level (LOAEL) of 30 mg/kg/day and a D-value of 0.003 mg/kg/day.