Subchronic Oral Toxicity of Silica Nanoparticles and Silica Microparticles in Rats.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.

[Immunotoxicologic assessment of genetically modified drought-resistant wheat T349 with GmDREB1].

OBJECTIVE: To assess the immunotoxicologic effects of genetically modified drought resistant wheat T349 with GmDREB1 gene. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats.

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.

Estrogen receptor α and ß expressions in hypothalamus-pituitary-ovary axis in rats exposed lactationally to soy isoflavones and bisphenol A.

OBJECTIVES: This paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones (SIF) and bisphenol A (BPA) and to examine estrogen receptor α (ERα) and estrogen receptor ß (ERß) expressions in hypothalamus-pituitary-ovary axis and uterus. METHODS: Maternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group. Dams in different treatment groups received corn oil (control), 150 mg/kg BW of SIF, 150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA, respectively, from postnatal day 5 to 11 (PND5-11) by gavage. On PND12 and PND70, 10 female litters were killed and hypothalamus, pituitary, ovary and uterus were collected. ERα and ERß expressions in these organs were detected with Western blotting assay. And vaginal opening time and estrus cycle were examined in animals fed for PND70. RESULTS: On PND12, the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats (P<0.05). But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA. On PND 70, however, the relative uterine weight in each treatment group was not statistically different from that in the control group (P>0.05). Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group (P>0.05). Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERß expressions in hypothalamus, pituitary, ovary and uterus on PND12 and PND70. These regulation patterns for ERα and ERß were different in different organs at different time points. CONCLUSION: Lactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats, which disappeared in later life. But these data fail to suggest a possibility for synergic actions between SIF and BPA. It was also demonstrated that the uterotrophic effects of SIF and BPA exposure might, at least, involve modification of ERα or ERß expressions in the hypothalamus-pituitary-ovary axis.

Subchronic toxicity study on soy isoflavones in rats.

OBJECTIVE: To investigate the subchronic toxicity of soy isoflavones (SIF) in male rats. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

[Public health situation and needs assessment after Wenchuan earthquake in Anxian, Sichuan province].

OBJECTIVE: To explore the public health situation and needs in Anxian after Wenchuan earthquake so as to make an effective strategy for disease control and prevention. METHODS: 69 concentrated settlements with 100 residents were investigated. Probability proportion to size was adopted for sampling of 2200 residents from 687 scattered households (about 440 000 scattered residents). The content of this survey included drinking water, food hygiene, environment sanitation, planning immunity and medical health service, disease surveillance and so on. SPSS 16.0 was used for data analysis, and statistical interpretation was used to describe the results. RESULTS: 90.9% (31/66) resettled residents in Anxian lived in tents, 7.6% (5/66) lived in the movable-plate house, 93.3% (621/666) scattered households lived in tents and 71.9% (446/621) of them lived in tents which were built by residents themselves; the rate of drinking water disinfection in resettlement sites and scattered households were 97.1% (66/68) and 94.6% (650/687); 12.8% scattered residents had mouldy or food; 50% of resettlement sites raised animals; 43.6% (17/39) medical station didn't have bacterin inoculation service; 66.7% (10/15) lacked sufficient disinfection equipment; register rate was 50.0% (33/66) and report rate of symptoms and infectious diseases was 56.1% (37/66). CONCLUSION: There was still some risk of enteric and vector-borne diseases in Anxian, therefore, some tailored measures should be very important.

[Mental health assessment among scattered residents after Wenchuan earthquake in Anxian, Sichuan province].

OBJECTIVE: To explore the mental health status of residents scattered living in Anxian after Wenchuan earthquake so as to provide scientific basis for further mental health intervention. METHODS: A face to face interview was conducted among the scattered residents with designed questionnaire, which had three parts of the physical and emotional reaction, the relax methods and the social care and supports expected. Two-stage probability proportional to size (PPS) sample method was performed to sample 2184 from 0.44 million scattered residents in Anxian. On the basis of statistical description, mental health of different characteristics groups was compared. RESULTS: Three main symptoms of posttraumatic stress disorders in 2184 residents (11.23+/-3.44) were higher than the 103 fire victims in Hunan in 2003 (10.06+/-3.26), three factor scores of SCL-90 (5.76+/-1.74) were higher than normal in 1998 repair mode (n=23 891) (4.72+/-1.44), and the statistical difference was observed (t=10.77, P<0.05; t=706.04, P<0.05). Comparing the mental health of different groups, some significant differences were found by age, gender and education background. CONCLUSION: The earthquake disaster brought prevalent physical and emotional reaction. Elderly people, female, junior students need mental intervention immediately. Therefore, strengthen the mental education and assistance (especially in high risk groups) would be of more significance.

Gene knockout and overexpression analysis revealed the role of N-acetylmuramidase in autolysis of Lactobacillus delbrueckii subsp. bulgaricus ljj-6.

Autolysis of lactic acid bacteria (LAB) plays a vital role in dairy processing. During cheese making, autolysis of LAB affects cheese flavor development through release of intracellular enzymes and restricts the proliferation of cells in yogurt fermentation and probiotics production. In order to explore the mechanism of autolysis, the gene for the autolytic enzymes of L. bulgaricus, N-acetylmuramidase (mur), was cloned and sequenced (GenBank accession number: KF157911). Mur gene overexpression and gene knockout vectors were constructed based on pMG76e and pUC19 vectors. Recombinant plasmids were transformed into L. bulgaricus ljj-6 by electroporation, then three engineered strains with pMG76e-mur vector and fifteen engineered strains with pUC19-mur::EryBII were screened. The autolysis of the mur knockout strain was significantly lower and autolysis of the mur overexpressed strain was significantly higher compared with that of the wild type strain ljj-6. This result suggested that the mur gene played an important role in autolysis of L. bulgaricus. On the other hand, autolytic activity in a low degree was still observed in the mur knockout strain, which implied that other enzymes but autolysin encoded by mur were also involved in autolysis of L. bulgaricus.