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Higher olefins (HO) are a category of unsaturated hydrocarbons widely used in industry applications to make products essential for daily human life. Establishing safe exposure limits requires a solid data matrix that facilitates understanding of their toxicological profile. This in turn allows for data to be read across to other members of the category, which are structurally similar and have predictable physico-chemical properties. Five independent subchronic oral toxicity studies were conducted in Wistar rats with Oct-1-ene, Nonene, branched, Octadec-1-ene, Octadecene and hydrocarbon C12-30, olefin-rich, ethylene polymn. by product, at doses ranging from 20 to 1000 mg/kg bw. These HO were selected considering gut absorption, carbon chain length, double-bond position and carbon backbone structural variations. Generally, limited and non-adverse toxicity effects were observed at the end of the treatment for short carbon chain HO. For instance, alpha 2u-globulin nephropathy in the male rats and liver hypertrophy. No clear trend in systemic toxicity was linked to the double-bond position. Key factors for hazard assessment include absorption, carbon chain length, and branching, with Nonene, branched, identified as the worst-case substance. Taken together, the no observed adverse effect level (NOAEL) of each HO in these subchronic studies was set at the highest dose tested.

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This study aims to assess the acute and subchronic toxicity of Calculus Bovis Sativus (CBS), which is an ideal substitute for natural Calculus Bovis. After conducting a test of acute toxicity with KM mice of both sexes, it was determined that oral CBS had a lethal dosage (LD50) of greater than 9.26 g/kg BW. For ninety days, Wistar rats were fed on CBS orally at dosages of 0, 167, 501, and 1503 mg/kg BW/day, respectively, as part of the subchronic investigation. A comparison of the controls with the 1503 mg/kg and 501 mg/kg dosage groups revealed significant differences in the hematological and serum biochemical parameters, such as RBC, HGB, MONO%, PLT, LYMPH% and GLU, TP, ALB, and Ca2+, were observed. However, values of the above parameters fell within our laboratory's normal range. In terms of body weight, food intake, urinalysis, clinical chemistry, and pathology, no other adverse effects were observed. After 90 days of exposure, the no observed adverse effect level (NOAEL) of CBS in rats was determined to be 1503 mg/kg BW/day.

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ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana officinalis L., commonly known as "valerian", is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear. AIM OF THE STUDY: This study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR). MATERIALS AND METHODS: The genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague-Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague-Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR. RESULTS: AEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight. CONCLUSION: In vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.

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Selenium supplements are beneficial to human health, however, concerns regarding the toxicity of inorganic selenium have stimulated research on safer organic compounds. The main objective of this study was to develop a novel glucosamine-selenium compound (Se-GlcN), clarify its structure, and subsequently investigate its oral toxicity and in vitro anti-hepatitis B virus (HBV) activity. Electron microscopy, infrared, ultraviolet spectroscopy, nuclear magnetic resonance and thermogravimetric analyses revealed a unique binding mode of Se-GlcN, with the introduction of the Se-O bond at the C6 position, resulting in the formation of two carboxyl groups. In acute toxicity studies, the median lethal dose (LD50) of Se-GlcN in ICR mice was 92.31 mg/kg body weight (BW), with a 95 % confidence interval of 81.88-104.07 mg/kg BW. A 30-day subchronic toxicity study showed that 46.16 mg/kg BW Se-GlcN caused livers and kidneys damage in mice, whereas doses of 9.23 mg/kg BW and lower were safe for the livers and kidneys. In vitro studies, Se-GlcN at 1.25 µg/mL exhibited good anti-HBV activity, significantly reducing HBsAg, HBeAg, 3.5 kb HBV RNA and total HBV RNA by 45 %, 54 %, 84 %, 87 %, respectively. In conclusion, the Se-GlcN synthesized in this study provides potential possibilities and theoretical references for its use as an organic selenium supplement.

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Lithocarpus litseifolius although known as "Sweet Tea" (ST), has been traditionally accepted as a daily beverage and used as a folk medicine in southern China with little understanding of its potential toxicity. This study evaluated the safety of a water extract of ST by a subchronic toxicity study in Sprague-Dawley rats. A total of 80 rats were randomized divided into 4 groups with 10 males and 10 females in each group, treated with 2000, 1,000, 500 and 0 mg/kg body weight of ST extract by gavage for 90 days, respectively. The results of the study showed that ST extract did not induce treatment-related changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine indices, and histopathology in rats. The NOAEL of ST extract was observed to be 2000 mg/kg/day for rats of both sexes. These results indicated that ST extract was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products.

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ETHNOPHARMACOLOGICAL SIGNIFICANCE: Elsholtiza bodinieri Vaniot, belonging to the family Lamiaceae, has important medicinal value in Yunnan province of China. Traditionally, its aerial parts have been used as an ethnomedicine to treat diaphoresis, headache, fever, cough, pharyngitis, dyspepsia, and hepatitis. However, the safety assessment of E. bodinieri is still unexplored. AIM OF THE STUDY: This study aimed to investigate the phytochemical constituents of the hot water extract from E. bodinieri (HEEB) and evaluate the 14-day acute, 28-day subacute and 90-day subchronic toxicity by oral administration in Sprague-Dawley (SD) rats. MATERIALS AND METHODS: The chemical constituents of HEEB were analyzed by UHPLC-ESI-HRMS/MS. Firstly, SD rats were chosen for a single oral administration of the maximum dose of 5000 mg/kg to evaluate toxicity. Subsequently, consecutive 28-day subacute and 90-day subchronic toxicity assessments of HEEB were conducted on Sprague-Dawley (SD) rats through repeated doses of 2500, 1250, 625, and 312.5 mg/kg for the former, and 1500, 1000, and 500 mg/kg for the latter. For toxicity evaluation, hematology and serum biochemical indicators were determined, and major organs of the rats were collected to calculate organ coefficients. Additionally, hematoxylin-eosin (H&E) staining was performed on the collected tissues to assess histopathological changes induced by repeated oral administration of HEEB. RESULTS: A total of 23 compounds were identified by UHPLC-ESI-HRMS/MS analysis. Acute toxicity assessment revealed that oral administration of HEEB did not induce mortality and unnormal behavior changes in female rats over a 14-day period, suggesting that the approximate lethal dose (ALD) was higher than 5000 mg/kg. In consecutive 28-day and 90-day toxicity evaluations, HEEB doses of 2500 mg/kg and 1500 mg/kg resulted in hepatic and kidney tissue damage in both female and male rats, which was verified by the increased levels of AST, ALT, BUN, Na+, and Cl-. CONCLUSIONS: After the acute, 28-day subacute and 90-day subchronic toxicity evaluation, the No Observed Adverse Effect Level (NOAEL) was determined as 1000 mg/kg/day. These findings not only provided a safety information for its medicinal and edible application, but also promoted the further comprehensive development of this plant.

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Objectives: The study was carried out to assess the effect of zinc supplementation on changes in calcium homeostasis, and parathyroid gland, bone, and skeletal muscle histology in rats exposed to subchronic oral glyphosate-based herbicide (GBH, GOBARA®) toxicity. Methods: Sixty male Wistar rats in 6 equal groups (DW, Z, G1, G2, ZG1, ZG2) were used: DW and Z were given 2 mL/kg distilled water and 50 mg/kg of zinc chloride (2%), respectively; G1 and G2 received 187.5 mg/kg and 375 mg/kg of glyphosate (in GBH), respectively; ZG1 and ZG2 were pretreated with 50 mg/kg of zinc chloride before receiving glyphosate, 1 hour later, at 187.5 and 375 mg/kg, respectively. Treatments were by gavage once daily for 16 weeks. Serum calcium, vitamin D, and parathormone were estimated. Histopathological examination of parathyroid gland, femoral bone and biceps femoris muscle was done. Results: GBH exposure caused significant (P = .0038) decrease in serum calcium concentration in G1, significant (P = .0337) decrease in serum vitamin D concentration in G1, significant increases in parathormone in G1 (P = .0168) and G2 (P = .0079) compared to DW. Significant (P > .05) changes did not occur in the other parameters of G2 compared to DW. Dose-dependent effect in GBH exposure was not observed after comparing G1 and G2. Necrotic changes occurred in parathyroid gland cells, osteocytes, and muscle cells in G1 and G2. In ZG1 and ZG2, significant (P > .05) variations in the parameters were not observed and tissue lesions were absent. Conclusion: Subchronic GBH exposure impaired calcium homeostasis observed as hypocalcemia, hypovitaminemia D, and secondary hyperparathyroidism and caused tissue damage in parathyroid gland, bone, and muscle of rats and these were mitigated by zinc chloride pretreatment.

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Mulberry (Morus alba L) fruit is traditionally used in Chinese medicine and has several beneficial effects, such as hypoglycemic, hypolipidemic, and anti-oxidative effects. We previously developed the synbiotic mulberry (SM) containing probiotic Lactobacilli, prebiotic inulin, and mulberry powder. In food supplement development, toxicity is the most important criterion in food and drug regulations before commercialization. Thus, this study aimed to investigate the subchronic toxicity of SM in male and female Wistar rats to evaluate its biosafety. The subchronic toxicity study was conducted by daily oral administration of SM at doses of 250, 500, and 1000 mg/kgBW for 90 days. Male and female rats were evaluated for body weight, organ coefficients, biochemical and hematological parameters, and vital organ histology. The results showed no mortality or toxic changes in the subchronic toxicity study. These results suggested that no observed adverse effect level (NOAEL) of SM in male and female rats has been considered at 1000 mg/kgBW for subchronic toxicity study.

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As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.

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Idesia polycarpa, belonging to the Flacourtiaceae family, is a tall deciduous tree, widely distributed in some Asian countries. It is famous for its high yield of fruit known as oil grape, which is rich of linoleic acid and linolenic acid, and so on. To provide evidences for its safe use as food, subchronic toxicity of I. polycarpa fruit oil and no observed adverse effect level were performed in male and female specific pathogen-free Wistar rats. Based on the Organization for Economic Co-operation and Development guidelines, the oil was orally administered to rats by gavage at 0, 1.0, 2.0, and 4.0mL/kg.bw/day for 90 days, followed by a 28-day recovery period. The results showed that no sign of oil-related toxicity, clinically or histologically, was observed in both male and female rats. Although there was a slight increase or decrease in some indicators such as hematology, serum chemistry, and so on, those changes were all within the normal ranges, and as presented in the 90-day study, the oil exhibited no toxic effect compared to the control rats. I. polycarpa might be a potential excellent and healthy vegetable oil resource.

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Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the "no observed adverse effect level" of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.

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Tobacco stalk is a cellulose-rich material and a sustainable alternative to be applied as a plant-based nanofibrillated cellulose (NFC) source. NFC use has garnered attention in the development of oral pharmaceutical forms, despite concerns about its safety due to the adverse effects of nicotine on health. Therefore, we aimed at establishing the safety of NFC derived from tobacco stalk for its potential use as a novel pharmaceutical excipient, exploring its potential functions for tablet production. We conducted acute and subchronic oral toxicity tests in adult female Wistar rats. Initially, individual animals received sequential doses (175-5,000 mg·kg-1) for 24 hours followed by a careful observation of any toxic effects. Subsequently, 20 rats were divided into four groups for a subchronic assay, evaluating toxicity signs, body weight changes, hematological, biochemical, and histopathological parameters. No deaths or other clinical toxicity signs were observed in either the acute or the subchronic assays. We noticed a significant reduction in body weight gain (p < 0.05) after 14 days. We found statistical differences for hematological and biochemical parameters, unrelated to dosage. There were no observed toxic effects, and tobacco stalk ingestion did not adversely affect organ morphology in the histopathological evaluation. The oral administration of NFC at 5,000 mg·kg-1 per day for 28 days was well-tolerated by treated rats, with no reported deaths. In conclusion, NFC derived from tobacco stalk has shown to be a sustainable and safe alternative for use as an excipient at experimental doses, demonstrating compatibility with its proposed applications.

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Spermidine is a polyamine consumed in the diet, endogenously biosynthesized in most cells, and produced by the intestinal microbiome. A variety of foods contribute to intake of spermidine along with other polyamines. Spermidine trihydrochloride (spermidine-3HCl) of high purity can be produced using an engineered strain of Saccharomyces cerevisiae. Spermidine has a demonstrated history of safe use in the diet; however, limited information is available in the public literature to assess the potential toxicity of spermidine-3HCl. To support a safety assessment for this spermidine-3HCl as a dietary source of spermidine, authoritative guideline and good laboratory practice (GLP) compliant in vitro genotoxicity assays (bacterial reverse mutation and mammalian micronucleus assays) and a 90-day oral (dietary) toxicity study in rats were conducted with spermidine-3HCl. Spermidine-3HCl was non-genotoxic in the in vitro assays, and no adverse effects were reported in the 90-day oral toxicity study up to the highest dose tested, 12500 ppm, equivalent to 728 mg/kg bw/day for males and 829 mg/kg bw/day for females. The subchronic no observed adverse effect level (NOAEL) is 728 mg/kg bw/day.

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The safety of a rhamnogalacturonan-I-enriched pectin extract (G3P-01) from pumpkin (Cucurbita moschata var. Dickinson) was evaluated for use as an ingredient in food and dietary supplements. G3P-01 was tested in a battery of genetic toxicity studies including reverse mutagenicity and in vitro micronucleus assay. In addition, Sprague-Dawley rats were randomized and orally dosed with G3P-01 incorporated in animal diet at concentrations of 0, 9000, 18,000, and 36,000 ppm daily for 13-weeks (n=10/sex/group) in line with OECD guidelines (TG 408). The results of the in vitro bacterial reverse mutation assay and micronucleus assay in TK6 cells demonstrated a lack of genotoxicity. The 13-week oral toxicity study in Sprague-Dawley rats demonstrated that the test article, G3P-01 was well tolerated; there were no mortalities and no adverse effects on clinical, gross pathology, hematology, blood chemistry, and histological evaluation of the essential organs of the animals. The present study demonstrates that G3P-01 is non-genotoxic and is safe when ingested in diet at concentrations up to 36, 000 ppm. The subchronic no-observed-adverse-effect level (NOAEL) for G3P-01 was concluded to be 36,000 ppm, equivalent to 1,899 and 2,361 mg/kg/day for male and female rats respectively.

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Objective: The aim of these studies was to ascertain if Camelina sativa oil is harmful in both the acute and subchronic states. Methods: Wistar rats of both sexes were used in an acute toxicity test, and the fatal dosage (LD50) of oral Camelina sativa oil was greater than 27.6 g/kg bw. Rats were gavaged with Camelina sativa oil at dosages of 0.00, 0.92, 1.84, and 3.68 g/kg bw per day for 90 days. In addition, satellite groups were established in the control and high-dose groups for a 28-day recovery period. The following factors were assessed: mortality, clinical anomalies, body weight, food intake, hematological, serum biochemistry, urine, gross necropsy, and histology. Results: There were no observable toxicity-related changes in any of the three dosage groups. There is no toxicological relevance to the change in the high-dose hematological indicator PLT at the conclusion of the recovery period because it was within the usual range for this strain in our laboratory. The test material did not result in any pathological alterations, according to a pathological examination. Conclusion: Since the results of the current study, the no-observed-adverse-effect-level (NOAEL) for Camelina sativa oil in rats has been determined to be greater than 3.68 g/kg bw.

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Huobahua, namely, Tripterygium hypoglaucum (Levl.) Hutch, known as a traditional Chinese herbal medicine, especially its underground parts, has been widely developed into several Tripterygium agents for the treatment of rheumatoid arthritis and other autoimmune diseases. It has sparked wide public concern about its safety, such as multi-organ toxicity. However, the toxic characteristics and damage mechanism of Huobahuagen extract (HBHGE) remain unclear. In the present study, subchronic oral toxicity study of HBHGE (10.0 g crude drug/kg/day for 12 weeks) was performed in male rats. Hematological, serum biochemical, and histopathological parameters, urinalysis, and plasma metabolic profiling were assessed. The single-dose subchronic toxicity results related to HBHGE exhibited obvious toxicity to the testis and epididymis of male rats. Furthermore, plasma metabolomics analysis suggested that a series of metabolic disorders were induced by oral administration of HBHGE, mainly focusing on amino acid (glutamate, phenylalanine, and tryptophan) metabolisms, pyrimidine metabolism, glutathione metabolism, and steroid hormone biosynthesis. Moreover, it appeared that serum testosterone in male rats treated with HBHGE for 12 weeks, decreased significantly, and was susceptible to the toxic effects of HBHGE. Taken together, conventional pathology and plasma metabolomics for preliminarily exploring subchronic toxicity and underlying mechanism can provide useful information about the reduction of toxic risks from HBHGE and new insights into the development of detoxification preparations.

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There are several technical challenges and public issues concerning genome editing applications before they become viable in commercial aquaculture. Recently, we developed a novel strategy to generate all-female (AF) common carp, which exhibited a growth advantage over the control carp, using genetic editing through single gene-targeting manipulation. Here, we found that the body weight of the AF common carp was higher by 22.58% than that of the control common carp. Because the genotype of the AF common carp was cyp17a1+/-;XX, the contents of sex steroids were normally synthesized, as they were comparable to that of the control female carp. To evaluate the food safety of the AF carp, Wistar rats were fed a diet containing control female carp (control, C) or all-female (AF) carp at an incorporation rate of 5, 10 and 20% (w/w) for 90 days. Compared with those fed control carp, the rats fed AF common carp exhibited no significant difference in body weight, food intake, feed conversion ratio, hematology, serum biochemistry, urine test, relative organ weight, gross necropsy, and histopathological examination. This is the first food safety assessment of the farmed fish strain cultured using CRISPR/Cas9, which will further advance the fishery development of genome-edited animals.

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To evaluate and compare the safety of four selenium supplements, namely Se-enriched peptides (SeP), yeast selenium (SeY), L-Se-methylselenocysteine (L-SeMc) and sodium selenite (Na2SeO3), the subchronic toxicity study was designed by 90-day gavage administration in Sprague-Dawley rats. The doses of SeP, SeY, L-SeMc and Na2SeO3 were 0.15, 0.30 and 0.60 mg/kg bw/day, with additional dose of 0.45 mg/kg L-SeMc (All dose calculated as Se). Symptoms like growling, hair loss and significant weight loss were found at 0.60 mg/kg of L-SeMc, but not in other groups. At the dose of 0.60 mg/kg, females in Na2SeO3, SeY and L-SeMc groups showed significant elevations in ALT and/or ALP. Pathologic manifestations such as bile duct hyperplasia and cholestasis were predominantly found in females at 0.6 mg/kg of L-SeMc and SeY groups, and in males at same dose of L-SeMc group showed marked testicular atrophy. 0.60 mg/kg of SeY and Na2SeO3, and 0.30, 0.45, 0.60 mg/kg of L-SeMc induced significant reductions in sperm motility rates, rapid movement and amount. In conclusion, the NOAEL of SeP, SeY, L-SeMc, Na2SeO3 was all 0.30 mg/kg for female, and 0.60, 0.30, 0.15 and 0.30 mg/kg for male respectively. Liver and reproductive organs are possible toxic target organs of hyper selenium.

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Collagen peptides are widely employed as therapeutic materials due to their numerous beneficial properties, including for the following uses: antiaging, antioxidant applications, antibacterial applications, wound healing, tissue engineering, medication delivery, and cosmetics. Although collagen peptides are useful in these applications, to our knowledge, few published studies have been undertaken on their repeated-dose toxicity. We evaluated the possible subchronic toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in Sprague-Dawley rats by administering repeated oral doses over 90 days. Rats of both sexes were assigned randomly to one of four experimental groups, respectively receiving 0, 500, 1000, or 2000 mg/kg/day of CPSS. At all doses tested, repeated oral CPSS administration had no treatment-related adverse effects in terms of clinical signs, body weight, food consumption, detailed clinical observation, sensory reactivity, functional assessment, urinalysis, ophthalmic examination, gross pathology, hematology, serum biochemistry, hormone analysis, organ weight, and histopathology. Even though there were some alterations in hematologic parameters, serum biochemistry parameters, organ weight, and histopathological findings, these did not follow a dose-response pattern and were within historical limits for control rats. The oral no-observed-adverse-effect level (NOAEL) of the CPSS was 2000 mg/kg/day for both male and female rats in the applied experimental circumstances, and no target organs were identified.

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Allitol is a hexitol produced by reducing the rare sugar D-allulose with a metal catalyst under hydrogen gas. To confirm the safe level of allitol, we conducted a series of safety assessments. From the results of Ames mutagenicity assay using Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, Escherichia coli strain WP2uvrA, and an in vitro chromosomal aberration test on cultured Chinese hamster cells, allitol did not show any significant genotoxic effect. No significant effects on general condition, urinalysis, hematology, physiology, histopathology, or at necropsy were observed at a dose of 1500 mg/kg body weight of allitol in the acute and 90-day subchronic oral-toxicity assessments for rats. A further study performed on healthy adult humans showed that the acute use level of allitol for diarrhea was 0.2 g/kg body weight for both men and women. The results of current safety assessment studies suggest that allitol is safe for human consumption.

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