Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats / 生物医学与环境科学（英文）

Objective@#The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake.@*Methods@#DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD.@*Results@#Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.@*Conclusion@#The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.

Lipid Accumulation and IL-6 Production in L02 Hepatocytes Induced by Sodium Oleate: Dose and Time Dependence / 生物医学与环境科学（英文）

To explore interleukin-6 (IL-6) production and characterize lipid accumulation in L02 hepatocytes induced by sodium oleate. L02 hepatocytes were incubated with 0, 37.5, 75, 150, 300, 600, or 1,200 μmol/L sodium oleate for 24 h, and the supernatant was collected to detect the concentration of IL-6. L02 hepatocytes were incubated with 300, 150, 75, or 0 μmol/L sodium oleate for 0-24 h. The supernatant was collected for detection of IL-6 and free fatty acids. L02 hepatocytes treated with 300 μmol/L sodium oleate for 0-24 h were stained with Oil Red O. With extended sodium oleate incubation time, IL-6 levels increased, and free fatty acids decreased. After 24 h incubation, IL-6 levels increased as sodium oleate increased from 37.5 to 300 μmol/L (

Subchronic Oral Toxicity of Silica Nanoparticles and Silica Microparticles in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the subchronic oral toxicity of silica nanoparticles (NPs) and silica microparticles (MPs) in rats and to compare the difference in toxicity between two particle sizes.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7, 500, and 1,500 mg/(kg•bw•day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver, kidneys, and testis were determined.</p><p><b>RESULTS</b>There were no toxicologically significant changes in mortality, clinical signs, body weight, food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups.</p><p><b>CONCLUSION</b>Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.</p>

Subchronic Oral Toxicity Evaluation of Lanthanum: A 90-day, Repeated Dose Study in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level (NOAEL), which is a critical factor in the establishment of an acceptable dietary intake (ADI).</p><p><b>METHODS</b>In accordance with the Organization for Economic Co-operation and Development (OECD) testing guidelines, lanthanum nitrate was administered once daily by gavage to Sprague-Dawley (SD) rats at dose levels of 0, 1.5, 6.0, 24.0, and 144.0 mg/kg body weight (BW) per day for 90 days, followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups. Outcome parameters were mortality, clinical symptoms, body and organ weights, serum chemistry, and food consumption, as well as ophthalmic, urinary, hematologic, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.</p><p><b>RESULTS</b>Significant decreases were found in the 144.0 mg/kg BW group in the growth index, including body weight, organ weights, and food consumption. This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day. Importantly, the 95% lower confidence value of the benchmark dose (BMDL) was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.</p><p><b>CONCLUSION</b>The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements (REEs).</p>

Effects of Parental Dietary Exposure to GM Rice TT51 on the Male Reproductive System of Rat Offspring / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the health effects of parental dietary exposure to GM rice TT51 on the male reproductive system of rat off spring.</p><p><b>METHODS</b>Rice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats (15 males/30 females each group) for 70 days prior mating and throughout pregnancy and lactation. After weaning, eight male offspring rats were randomly selected at each group and fed with diets correspondent to their parents' for 70 days. The effects of exposure to TT51 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serum hormones (FSH, LH, and testosterone levels), testis histopathological examination, and the relative expression levels of selected genes along the hypothalamic-pituitary- testicular (HPT) axis.</p><p><b>RESULTS</b>No significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis.</p><p><b>CONCLUSION</b>The results of this study demonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.</p>

Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats.</p><p><b>METHODS</b>Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70.</p><p><b>RESULTS</b>No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results.</p><p><b>CONCLUSION</b>Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.</p>

Immunotoxicity of acrylamide in female BALB/c mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the immunotoxicity of acrylamide (ACR) in female BALB/c mice.</p><p><b>METHODS</b>A total of 200 female mice weighing 18-22 g were randomly divided into four clusters based on body weight, and each weight-based cluster included five groups (10 mice per group): negative control, positive control (cyclophosphamide), low, intermediate, and high dose ACR groups, and all the groups were administered ACR by gavage for 30 days. At the end of the study, the immunotoxicological effects of the ACR were evaluated through immunopathology, humoral immunity, cellular immunity, and non-specific immunity.</p><p><b>RESULTS</b>The terminal body weight, spleen and thymus weights, lymphocyte counts in the ACR-H group were decreased, pathological changes were observed in lymph glands, thymus and spleen. %T cells in blood lymphocytes were significantly increased in all ACR-treated groups, and a significant reduction of % natural killer(NK) cells and increase of %Th cells were observed in the ACR-H group. interleukin-6(IL-6), Concanavalin A(ConA)-induced splenocyte proliferation and serum half hemolysis value (HC50) were also significantly suppressed in the ACR-H group.</p><p><b>CONCLUSION</b>ACR elicited an inhibitory effect on cellular and humoral immunity of mice after 30 day feeding.</p>

Endocrine disruption of cadmium in rats using the OECD enhanced TG 407 test system / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the endocrine disrupting effects of cadmium (Cd) using OECD enhanced TG407 test guideline.</p><p><b>METHODS</b>Sprague-Dawley (SD) rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg•BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary β2-microglobulin, organ weights and histopathology and estrous cycle were detected.</p><p><b>RESULTS</b>Cd could significantly decrease animals' body weight (P<0.05). Serum luteinizing hormone (LH) at 10-20 mg/kg•BW groups and testosterone (T) at 2.5 and 10 mg/kg•BW groups decreased significantly (P<0.05). However, no statistically significant change was found in urinary β2-microglobulin among Cd-treatment groups (P>0.05). Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg•BW groups showed significant increase (P<0.05). While among male rats in 2.5, 10, 20 mg/kg•BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased (P<0.05). Moreover, no histopathological change was observed in kidney.</p><p><b>CONCLUSION</b>Results suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.</p>

Combined subchronic toxicity of bisphenol A and dibutyl phthalate on male rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the combined subchronic toxicity of bisphenol A (BPA) and dibutyl phthalate (DBP) in male Sprague Dawley (SD) rats.</p><p><b>METHODS</b>Forty 4-week-old male rats weighing 115-125 g were randomly divided into BPA-treated, DBP-treated group, BPA+DBP-treated and control groups and fed with a soy- and alfalfa-free diet containing 285.4 ppm BPA, 285.4 ppm DBP, 285.4 ppm BPA plus 285.4 ppm DBP, and a control diet, respectively, for 90 consecutive days. At the end of the study, the animals were sacrificed by exsanguination via the carotid artery under diethyl etherane aesthesia and weighed. Organs, including liver, kidneys, spleen, thymus, heart, brain, and testis underwent pathological examination. The androgen receptor (AR), gonadotropin-releasing hormone receptor (GNRHR), and progesterone hormone receptor (PR) genes from the hypothalamus were detected by real-time PCR. The biomedical parameters were analyzed.</p><p><b>RESULTS</b>No significant difference was found in food intake, body weight, tissue weight, organ/brain weight ratio, and biomedical parameters among the four groups (P>0.05). However, BPA and DBP up-regulated AR, PR and GNRHR expression levels in rats and showed a synergistic or an additive effect in the BPA+DBP group.</p><p><b>CONCLUSION</b>The combined subchronic toxicity of BPA and DBP is synergistic or additive in male SD rats.</p>

Immunotoxicological evaluation of wheat genetically modified with TaDREB4 gene on BALB/c mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the immunotoxicological effects of genetically modified wheat with TaDREB4 gene in female BALB/c mice.</p><p><b>METHODS</b>Female mice weighing 18-22 g were divided into five groups (10 mice/group), which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. Mice in negative control group and positive control group were fed with AIN93G diet, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat (the proportion is 76%) for 30 days, then body weight, absolute and relative weight of spleen and thymus, white blood cell count, histological examination of immune organ, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell, serum half hemolysis value, mitogen-induced splenocyte proliferation, delayed-type hypersensitivity reaction and phagocytic activities of phagocytes were detected.</p><p><b>RESULTS</b>No immunotoxicological effects related to the consumption of the genetically modified wheat were observed in BALB/c mice when compared with parental wheat group, common wheat group and negative control group.</p><p><b>CONCLUSION</b>From the immunotoxicological point of view, results from this study demonstrate that genetically modified wheat with TaDREB4 gene is as safe as the parental wheat.</p>

Immunotoxicologic assessment of genetically modified drought-resistant wheat T349 with GmDREB1 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To assess the immunotoxicologic effects of genetically modified drought resistant wheat T349 with GmDREB1 gene.</p><p><b>METHODS</b>A total of 250 female BALB/c mice (6-8 week-old, weight 18-22 g) were divided into five large groups (50 mice for each large group) by body weight randomly. In each large group, the mice were divided into five groups (10 mice for each group) by body weight randomly, which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. Mice in negative control and positive control group were fed with feedstuff AIN-93G, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat (proportion up to 76%) for 30 days, then body weight, organ coefficient of spleen and thymus, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell (PFC), serum 50% hemolytic value (HC50), mitogen-induced splenocyte proliferation, delayed-type hypersensitivity (DTH) reaction and phagocytic activities of phagocytes were detected respectively.</p><p><b>RESULTS</b>After 30 days raise, among negative control group, common wheat group, non-genetically modified parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, mice body weight were (21.0±0.3), (20.4±0.7), (21.1±1.0), (21.1±1.0), (19.4±1.0) g, respectively (F=7.47, P<0.01); organ coefficient of spleen were (0.407±0.047)%, (0.390±0.028)%, (0.402±0.042)%, (0.421±0.041)%, (0.304±0.048)%, respectively (F=12.41, P<0.01); organ coefficient of thymus were (0.234±0.032)%, (0.246±0.028)%, (0.249±0.040)%, (0.234±0.034)%, (0.185±0.039)%, respectively (F=5.58, P<0.01); the percentage of T cell in peripheral blood were (70.43±4.44)%, (68.33±5.37)%, (73.04±2.68)%, (74.42±2.86)%, (90.42±1.66)%, respectively (F=57.51, P<0.01); the percentage of B cell were (13.89±3.19)%, (15.34±4.84)%, (13.06±4.22)%, (12.93±2.36)%, (3.01±0.96)%, respectively (F=12.79, P<0.01); the percentage of Th cell were (55.87±3.80)%, (55.24±4.60)%, (57.92±3.70)%, (59.57±2.54)%, (77.37±2.31)%, respectively (F=68.58, P<0.01);the Th/Ts ratio were 4.16±0.29, 4.73±0.96, 4.19±0.78, 4.52±0.40, 6.34±0.73, respectively (F=17.57, P<0.01);the serum IgG were (1046.38±210.67), (1065.49±297.22), (1517.73±299.52), (1576.67±241.92), (1155.88±167.05) µg/ml, respectively (F=10.53, P<0.01); the serum IgM were (333.83±18.97), (327.73±27.72), (367.47±27.18), (363.42±46.14), (278.71±24.42) µg/ml, respectively (F=12.11, P<0.01); the serum IgA were (51.69±10.10), (42.40 ± 8.35), (32.11±4.22), (37.12±4.90), (41.45±8.89) µg/ml, respectively (F=8.25, P<0.01); the PFC were (29.2±14.6), (28.0±20.0), (34.8±30.9), (33.2±25.1), (4.8±5.3) per 10(6) splenocyte, respectively (F=3.33, P<0.05); the HC50 were 82.3±6.5, 79.7±4.6, 75.8±4.1, 74.9±3.6, 70.8±2.1, respectively (F=9.99, P<0.01);the LPS-induced splenocyte proliferation were 0.21±0.10, 0.21±0.14, 0.26±0.12, 0.25±0.14, 0.07±0.06, respectively (F=4.18, P<0.05).</p><p><b>CONCLUSION</b>The genetically modified drought-resistant wheat T349 was substantially equivalent to parental wheat in the effects on immune organs and immunologic functions of mice, and it didn't show immunotoxicity.</p>

Subchronic toxicity study on soy isoflavones in rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the subchronic toxicity of soy isoflavones (SIF) in male rats.</p><p><b>METHOD</b>Fifty Sprague-Dawley rats were randomly divided into 5 groups, 10 rats per group. SIF were given to rats in different groups by gavage at dose of 0, 0.2, 0.5, 1.5, and 4.5 g/kg bw, respectively for 13 weeks. Clinical manifestations, body weight, and food consumption were observed weekly. At the end of the study, urinalysis, hematology, clinical chemistry, total testosterone, and follicle-stimulating hormone were tested, and histopathological examinations were performed.</p><p><b>RESULTS</b>No mortality, ophthalmic abnormalities or treatment-related clinical signs were identified during the study. As compared with the control group, significantly lower body weights and food consumption were observed in 1.5 and 4.5 g/kg bw groups. In clinical chemistry tests, triglyceride was significantly decreased and high-density lipoprotein cholesterol was significantly increased in all SIF-treated groups. Total testosterone levels were significantly lower in 0.50, 1.50, and 4.5 g/kg bw dose groups than in the control group. Microscopic examination showed that the mammary glands exhibited hyperplasia and excreted latex in rats of the 4.5 g/kg bw group. No changes attributable to treatment of SIF in other parameters were found.</p><p><b>CONCLUSION</b>SIF at high dosages caused significant endocrine disruption in male rats. The no observed adverse effect level (NOAEL) of SIF to male rats in this study is considered to be 0.20 g/kg bw.</p>

Assessment on dietary melamine exposure from tainted infant formula / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To estimate the dietary melamine exposure in Chinese infants and young children from the consumption of melamine adulterated Sanlu infant formula.</p><p><b>METHODS</b>Four age groups of infants and young children (3, 6, 12, and 24 months) were chosen as the assessed subjects and the maximum amount of infant formula consumption was estimated based on the recommended usage level in the package insert of Sanlu infant formula and other brands. Melamine was analyzed in 111 Sanlu infant formula samples collected from the markets in Beijing and Gansu province using the LC-MS-MS with a limit of quantification of 0.05 mg/kg. Four levels of melamine concentration were chosen to estimate the dietary intakes, including the mean, median, 90th percentile, and maximum.</p><p><b>RESULTS</b>The infants of 3 months had the highest intake of melamine, and with the increase of the age (month), the intake decreased. Based on the median melamine concentration (1,000 mg/kg) as an example, the melamine intakes for the infants of 3, 6, 12, and 24 months were 23.4, 21.4, 15.0, and 8.6 mg/kg bw/d, respectively.</p><p><b>CONCLUSION</b>Dietary melamine intakes from tainted Sanlu infant formula significantly exceeded the TDI level (0.2 mg/kg bw/d) recommended by the WHO Expert Meeting in 2008. However, the present assessment has some limitations including the poor representative samples, the varied melamine concentrations in the adulterated Sanlu infant formula, and other brand infant formula possibly consumed by these infants.</p>

Effects of tea polyphenols and tea pigments on telomerase activity of HepG2 cells / 中华预防医学杂志

<p><b>OBJECTIVE</b>This study is to investigate the effect of tea polyphenols and tea pigments on telomerase activity of human liver cancer cell line, HepG2 cells.</p><p><b>METHODS</b>TRAP-PCR-ELISA was applied to investigate the telomerase activity.</p><p><b>RESULTS</b>Telomerase was positive in tea polyphenols treated groups, tea pigments treated groups and blank control group. Telomerase activities (A(450 approximately 690) values) were 1.56 and 1.46 in 50 mg/L and 100 mg/L tea polyphenols-treated groups, 1.55 and 1.49 in 50 mg/L and 100 mg/L tea pigments-treated groups, respectively. The results showed that telomerase activity was significantly inhibited by tea polyphenols and tea pigments treatment as compared with the blank control group (A(450 approximately 690) = 2.11).</p><p><b>CONCLUSIONS</b>Tea polyphenols and tea pigments could significantly inhibit telomerase activity of HepG2 cells, and telomerase activity may be a useful biomarker for cancer chemoprevention.</p>