Safety Assessment of Soy Proteins and Peptides as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of soy proteins and peptides, which function in cosmetics primarily as hair conditioning agents and skin-conditioning agents-miscellaneous. The Panel considered relevant data related to these ingredients. The Panel concluded that soy proteins and peptides are safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Soybean protein concentrate as a protein source for totoaba (Totoaba macdonaldi) juveniles: Effect on intermediary metabolism and liver histological organization.

This study aimed to investigate the effects of replacing fish meal (FM) with soybean protein concentrates (SPC) on the intermediary metabolism and health of Totoaba macdonaldi juveniles. Fish (initial weight 50 ± 1 g) were fed for 60 days with eight diets: a reference diet (RD) and seven experimental diets where FM was replaced gradually with 15 to 100% SPC (SPC15, SPC30, SPC45, SPC60, SPC75, SPC90, and SPC100, respectively). Hexokinase (HK), glucokinase (GK), and alanine aminotransferase (ALT) enzyme activities showed highly significant differences (p < 0.01) between fish fed RD (0% SPC) compared to fish fed the diets with 60, 75, 90, and 100% SPC. The ALT enzyme shows a highly significant (p < 0.01) decrease in activity for fish fed 75, 90, and 100% SPC inclusions compared to fish fed the RD. The aspartate aminotransferase AST/ALT ratio showed a significant increase in activity for fish fed 100% soybean compared only with fish fed the control diet. The histological organization of the liver in totoaba juveniles fed RD, SPC15, SPC30 and SPC45 diets were similar. Totoaba fed with SPC90 and SPC100 showed histological alterations in hepatic and pancreatic parenchyma. Overall, according to the findings in this study, 45% of dietary FM could be replaced by SPC without causing adverse changes in metabolism, histological organization of liver, and health of juveniles of totoaba when cultured for 60 days. However, levels greater than 60% of SPC could compromise the health status of fish.

Transcriptome analysis reveals the hepatoprotective mechanism of soybean meal peptides against alcohol-induced acute liver injury mice.

This study aimed was to explore the hepatoprotective potential of soybean meal peptides (SPs) against alcohol-induced liver injury and investigate the underlying mechanisms through transcriptome analysis. The chemical antioxidant analysis of SPs exhibited potent ABTS radical scavenging capacity (11.94 ± 0.41 mg TE/100 mg peptide), ferric reducing antioxidant power (6.42 ± 0.32 mmol Fe2+/100 mg peptide), and oxygen radical absorption capacity (14.78 ± 0.01 mg TE/100 mg peptide). Moreover, SPs increased cell viability and reduced intracellular reactive oxygen species levels in Caco-2 cells by H2O2-induced, and without cytotoxicity. In the mice model, preintervention with SPs reduced the levels of aspartate transaminase/alanine transaminase, total cholesterol, triglyceride and malondialdehyde by alcohol-induced, meanwhile, increased the levels of total superoxide dismutase, glutathione and catalase by alcohol-induced. Histological analysis showed that SPs alleviated the liver injury by alcohol-induced and no toxic effects on the kidneys. According to transcriptome analysis, 1737 genes were significantly differentially expressed (1076 up-regulated and 661 down-regulated) after SPs pretreatment. The main functions of these genes were related to inflammation, lipid metabolism and oxidation. The findings from the present study suggested that SPs produced positive hepatoprotection and showed potential to be used as a dietary supplement or an ingredient of functional food.

N-Acetylcysteine improves intestinal function and attenuates intestinal autophagy in piglets challenged with ß-conglycinin.

ß-Conglycinin (ß-CG), an anti-nutritional factor, is a major allergen in soybeans to induce intestinal dysfunction and diarrhea in neonatal animals, including piglets and human infants. This study with a piglet model determined the effects of N-acetylcysteine (NAC) on intestinal function and autophagy in response to ß-CG challenge. Twenty-four 12-day-old piglets (3.44 ± 0.28 kg), which had been weaned at 7 days of age and adapted for 5 days after weaning, were randomly allocated to the control, ß-CG, and ß-CG + NAC groups. Piglets in the control group were fed a liquid diet containing 10% casein, whereas those in the ß-CG and ß-CG + NAC groups were fed the basal liquid diets containing 9.5% casein and 0.5% ß-CG for 2 days. Thereafter, pigs in the ß-CG + NAC group were orally administrated with 50 mg (kg BW)-1 NAC for 3 days, while pigs in the other two groups were orally administrated with the same volume of sterile saline. NAC numerically reduced diarrhea incidence (- 46.2%) and the concentrations of hydrogen peroxide and malondialdehyde, but increased claudin-1 and intestinal fatty-acid binding protein (iFABP) protein abundances and activities of catalase and glutathione peroxidase in the jejunum of ß-CG-challenged piglets. Although ß-CG challenge decreased the villus height, villus height/crypt depth ratio, and mRNA levels of claudin-1 and occludin, no significant differences were observed in these indices between the control and ß-CG + NAC groups, suggesting the positive effects of NAC supplementation on intestinal mucosal barrier function. Moreover, NAC increased the concentrations of citrulline and D-xylose in the plasma, as well as the expression of genes for aquaporin (AQP) 3, AQP4, peptide transporter 1 (PepT1), sodium/glucose co-transporter-1 (SGLT-1), potassium inwardly-rectifying channel, subfamily J, member 13 (KCNJ13), and solute carrier family 1 member 1 (SLC1A1) in the jejunum, demonstrating that NAC augmented intestinal metabolic activity and absorptive function. Remarkably, NAC decreased Atg5 protein abundance and the LC3II/LC3I ratio (an indicator of autophagy) in the jejunum of ß-CG-challenged piglets. Taken together, NAC supplementation improved intestinal function and attenuated intestinal autophagy in ß-CG-challenged piglets.

MHC II-PI3K/Akt/mTOR Signaling Pathway Regulates Intestinal Immune Response Induced by Soy Glycinin in Hybrid Grouper: Protective Effects of Sodium Butyrate.

Soy glycinin (11S) is involved in immune regulation. As an additive, sodium butyrate (SB) can relieve inflammation caused by 11S. To further delve into the mechanisms. A diet containing 50% fishmeal was the control group (FM group), and the experimental groups consisted of the FM group baseline plus 2% glycinin (GL group), 8% glycinin (GH group), and 8% glycinin + 0.13% sodium butyrate (GH-SB group). The specific growth ratio (SGR), feed utilization, and density of distal intestinal (DI) type II mucous cells were increased in the GL group. In the serum, IFN-γ was significantly upregulated in the GL group, and IgG and IL-1ß were upregulated in the GH group. IgG, IL-1ß, and TNF-α in the GH-SB group were significantly downregulated compared to those in the GH group. The mRNA levels of mTOR C1, mTOR C2, and Deptor were upregulated in the GL, GH, and GH-SB groups in the DI compared with those in the FM group, while the mRNA levels of mTOR C1 and Deptor in the GH group were higher than those in the GL and GH-SB groups. 4E-BP1, RICTOR, PRR5, MHC II, and CD4 were upregulated in the GH group. TSC1, mLST8, and NFY mRNA levels in the GL and GH-SB groups were upregulated compared with those in the FM and GH groups. Western blotting showed P-PI3KSer294/T-PI3K, P-AktSer473/T-Akt, and P-mTORSer2448/T-mTOR were upregulated in the GH group. Collectively, our results demonstrate that low-dose 11S could improve serum immune by secreting IFN-γ. The overexpression of IgG and IL-1ß is the reason that high-dose 11S reduces serum immune function, and supplementing SB can suppress this overexpression. Low-dose 11S can block the relationship between PI3K and mTOR C2. It can also inhibit the expression of 4E-BP1 through mTOR C1. High-dose 11S upregulates 4E-BP2 through mTOR C1, aggravating intestinal inflammation. SB could relieve inflammation by blocking PI3K/mTOR C2 and inhibiting 4E-BP2. Generally speaking, the hybrid grouper obtained different serum and DI immune responses under different doses of 11S, and these responses were ultimately manifested in growth performance. SB can effectively enhance serum immunity and relieve intestinal inflammation caused by high dose 11S.

Soybean glycinin decreased growth performance, impaired intestinal health, and amino acid absorption capacity of juvenile grass carp (Ctenopharyngodon idella).

The present study evaluated the influence of dietary soybean glycinin on growth performance, intestinal morphology, free intestinal amino acid (AA) content, and intestinal AA transporter (AAT) mRNA levels in juvenile grass carp (Ctenopharyngodon idella). Results were displayed as follows: (1) 8% dietary glycinin decreased growth performance, inhibited intestinal growth, and caused intestinal histology damage of grass carp; (2) dietary glycinin decreased the content of free neutral AAs including Val, Ser, Tyr, Ala, Pro, and Gln in all intestinal segments, and Thr, Ile, Leu, Phe, and Gly in the MI and DI while downregulated the mRNA levels of corresponding transporters including SLC38A2, SLC6A19b, and SLC6A14 in all intestinal segments, and SLC7A5, SLC7A8, and SLC1A5 in the MI and DI. Dietary glycinin decreased the content of free basic AAs including Arg in the MI and DI and His in all intestinal segments while downregulated cationic AAT SLC7A1 mRNA levels in the MI and DI. Dietary glycinin decreased the content of free acidic AAs including Glu in all intestinal segments and Asp in the MI and DI while decreased mRNA levels of corresponding transporters including SLC1A2a in all intestinal segments and SLC1A3 in the MI and DI; (3) the digestion trial showed that basic subunits of glycinin was hard to digest in the intestine of grass carp; (4) co-administration of glutamine with glycinin partially alleviated the negative effects. Overall, glycinin decreased intestinal AA absorption capacity partly contributed by decreased AATs' mRNA levels and the indigestibility of glycinin.

Compatibility and safety of five lectin-binding putative probiotic strains for the development of a multi-strain protective culture for poultry.

The ban on the use of antibiotics as feed additives for animal growth promotion in the European Union and United States and the expectation of this trend to further expand to other countries in the short term have prompted a surge in probiotic research. Multi-species probiotics including safe and compatible strains with the ability to bind different nutritional lectins with detrimental effects on poultry nutrition could replace antibiotics as feed additives. Lactobacillus salivarius LET201, Lactobacillus reuteri LET210, Enterococcus faecium LET301, Propionibacterium acidipropionici LET103 and Bifidobacterium infantis CRL1395 have proved to be compatible as evaluated through three different approaches: the production and excretion of antimicrobial compounds, growth inhibition by competition for essential nutrients and physical contact, and a combination of both. The safety of P. acidipropionici LET103 was confirmed, since no expression of virulence factors or antibiotic resistance was detected. The innocuity of E. faecium LET301 should be further evaluated, since the presence of genes coding for certain virulence factors (gelE, efaAfm and efaAfs) was observed, albeit no expression of gelE was previously detected for this strain and there are no reports of involvement of efaAfm in animal pathogenicity. Finally, a combination of the five strains effectively protected intestinal epithelial cells of broilers from the cytotoxicity of mixtures of soybean agglutinin, wheat germ agglutinin and concanavalin A. To our knowledge, this is the first time that a combination of strains is evaluated for their protection against lectins that might be simultaneously present in poultry feeds.

Safety evaluation of soybean protein isolate oxidized by a hydroxyl radical-generating system.

The oxidative modification of soybean protein isolate (SPI) induced by a hydroxyl radical-generating system (HRGS) has a broad range of applications. However, few toxicology studies exist on this material. The safety of HRGS-oxidized SPI was assessed using subchronic and genotoxicity studies. A 30-day subchronic study (250, 500 and 1000 mg/kg∙BW) in rats showed no significant adverse effects on food consumption, body weight (BW), mortality, hematology, biochemistry, necropsy, organ weight or histopathology. The result of an Ames test showed that HRGS-oxidized SPI was not mutagenic to the test strains. The results of a bone marrow micronucleus test and mouse sperm abnormality test showed HRGS-oxidized SPI (417.5, 835.0 and 1670.0 mg/kg⋅BW) did not produce any aberrant effects on bone marrow cells or mouse sperm. Therefore, HRGS-oxidized SPI showed no genotoxicity in vivo or in vitro. In conclusion, these results support the safe use of HRGS-oxidized SPI as a food and dietary supplement.

Cytotoxic damage of soybean agglutinin on intestinal epithelial cells of broiler chicks: in vitro protection by Bifidobacterium infantis CRL1395.

Plant lectins, which are proteins/glycoproteins present in a wide range of vegetables, fruits, cereals and beans, are resistant to digestive enzymes and food cooking temperatures. They bind reversibly to specific glycosidic residues expressed on the membrane of intestinal epithelial cells (IEC) and cause anti-nutritional effects in humans and animals. Soybean lectin (SBA) has been detected in poultry diets, and its ability to bind to the intestinal epithelium has been reported. The development of new methods for removing SBA from feeds or to prevent interaction with the intestinal mucosa is of interest. In this study, the in vitro cytotoxicity of SBA on IEC of chicks was demonstrated for the first time. The LD50, assessed after 2 h exposure of IEC to SBA, was 6.13 µg mL(-1) The ability of Bifidobacterium infantis CRL1395 to bind SBA on the bacterial envelope was confirmed, and prevention of IEC cytotoxicity by lectin removal was demonstrated. Safety of B. infantis CRL1395, resistance to gastrointestinal stress and adhesion were also determined. It was concluded that the early administration of B. infantis CRL1395 to chicks would effectively reduce the toxicity of SBA. Besides, it would favour the colonization of the gut with a beneficial microbiota.

Soyabean glycinin depresses intestinal growth and function in juvenile Jian carp (Cyprinus carpio var Jian): protective effects of glutamine.

This study investigated the effects of glycinin on the growth, intestinal oxidative status, tight junction components, cytokines and apoptosis signalling factors of fish. The results showed that an 80 g/kg diet of glycinin exposure for 42 d caused poor growth performance and depressed intestinal growth and function of juvenile Jian carp (Cyprinus carpio var. Jian). Meanwhile, dietary glycinin exposure induced increases in lipid peroxidation and protein oxidation; it caused reductions in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities; and it increased MnSOD, CuZnSOD, GPx1b and GPx4a mRNA levels, suggesting an adaptive mechanism against stress in the intestines of fish. However, dietary glycinin exposure decreased both the activity and mRNA levels of nine isoforms of glutathione-S-transferase (GST) (α, µ, π, ρ, θ, κ, mGST1, mGST2 and mGST3), indicating toxicity to this enzyme activity and corresponding isoform gene expressions. In addition, glycinin exposure caused partial disruption of intestinal cell-cell tight junction components, disturbances of cytokines and induced apoptosis signalling in the distal intestines>mid intestines>proximal intestines of fish. Glycinin exposure also disturbed the mRNA levels of intestinal-related signalling factors Nrf2, Keap1a, Keap1b, eleven isoforms of protein kinase C and target of rapamycin/4E-BP. Interestingly, glutamine was observed to partially block those negative influences. In conclusion, this study indicates that dietary glycinin exposure causes intestinal oxidative damage and disruption of intestinal physical barriers and functions and reduces fish growth, but glutamine can reverse those negative effects in fish. This study provides some information on the mechanism of glycinin-induced negative effects.

Soy but not bisphenol A (BPA) or the phytoestrogen genistin alters developmental weight gain and food intake in pregnant rats and their offspring.

Endocrine disrupting compounds (EDCs) are hypothesized to promote obesity and early puberty but their interactive effects with hormonally active diets are poorly understood. Here we assessed individual and combinatorial effects of soy diet or the isoflavone genistein (GEN; administered as the aglycone genistin GIN) with bisphenol A (BPA) on body weight, ingestive behavior and female puberal onset in Wistar rats. Soy-fed dams gained less weight during pregnancy and, although they consumed more than dams on a soy-free diet during lactation, did not become heavier. Their offspring (both sexes), however, became significantly heavier (more pronounced in males) pre-weaning. Soy also enhanced food intake and accelerated female pubertal onset in the offspring. Notably, pubertal onset was also advanced in females placed on soy diet at weaning. Males exposed to BPA plus soy diet, but not BPA alone, had lighter testes. BPA had no independent effects.

Cellulose/soy protein isolate composite membranes: evaluations of in vitro cytocompatibility with Schwann cells and in vivo toxicity to animals.

OBJECTIVE: To evaluate the in vitro cytocompatibility of cellulose/soy protein isolate composite membranes (CSM) with Schwann cells and in vivo toxicity to animals. METHODS: A series of cellulose/soy protein isolate composite membranes (CSM) were prepared by blending, solution casting and coagulation process. The cytocompatibility of the CSM to Schwann cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and by direct cells culture of Schwann cells on the surfaces of the CSM, respectively. The in vivo toxicity of the CSM to animals were also evaluated by acute toxicity testing, skin sensitization testing, pyrogen testing and intracutaneous stimulation testing, respectively, according to the ISO 10993 standard. RESULTS: The MTT assay showed that the cell viability of Schwann cells cultured in extracts from the CSM was higher than that from the neat cellulose membrane without containing SPI component. The direct cells culture indicated that the Schwann cells could attach and grow well on the surface of the CSM and the incorporation of SPI into cellulose contributed to improvement of cell adhesion and proliferation. The evaluations of in vivo biological safety suggested that the CSM showed no acute toxicity, no skin sensitization and no intracutaneous stimulation to the experimental animals. CONCLUSION: The CSM had in vitro cytocompatibility with Schwann cells and biological safety to animals, suggesting potential for the applications as nerve conduit for the repair of nerve defect.

Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats.

We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10mg/kg) induce changes in the angio-follicular units of the thyroid gland, reduce concentration of total thyroid hormones (TH) and increase thyrotropin (TSH) in serum of orchidectomized middle-aged (16-month-old) rats. To further investigate these effects, we now examined expression levels of the thyroglobulin (Tg), thyroperoxidase (Tpo), vascular endothelial growth factor A (Vegfa) and deiodinase type 1 (Dio 1) genes in the thyroid; in the pituitary, genes involved in TH feedback control (Tsh ß, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T3-activated genes Dio 1 and Spot 14, as well as transthyretin (Ttr), by quantitative real-time PCR. We also analyzed TPO-immunopositivity and immunofluorescence of T4 bound to Tg, determined thyroid T4 levels and measured deiodinase enzyme activities in examined organs. Decreased expression of Tg and Tpo genes (p<0.05) correlated with immunohistochemical staining results, and together with decreased serum total T4 levels, indicates decreased Tg and TH synthesis following treatments with both isoflavones. However, expression of Spot 14 (p<0.05) gene in liver and kidney was up-regulated, and liver Dio 1 expression and activity (p<0.05) increased. At the level of pituitary, no significant change in gene expression levels, or Dio 1 and 2 enzyme activities was observed. In conclusion, both G and D impaired Tg and TH synthesis, but at the same time increased tissue availability of TH in peripheral tissues of Orx middle-aged rats.

Interactions between carboxymethyl konjac glucomannan and soy protein isolate in blended films.

To elucidate biopolymer interactions between carboxymethyl konjac glucomannan (CMKGM) and soy protein isolate (SPI) in different ratios on physicochemical properties of the blended films, biodegradable CMKGM/SPI films were prepared and characterized. The results showed that CMKGM and SPI are highly compatible in blended film formation, and that Maillard reactions and hydrogen bonds interactions between CMKGM and SPI occurred. The water adsorption of the CMKGM/SPI films progressively decreased with increasing CMKGM level, the surface wettability of the blended films was improved with increasing CMKGM content; the CMKGM/SPI blend films had enhanced tensile strength (TS) and elongation at break (EAB) compared to pure CMKGM and SPI films; the oxygen permeability of blend films was decreased; the roughness was decreased with increasing CMKGM content. Moreover, the CMKGM/SPI film was biocompatible and biodegradable.

Dietary soybean protein concentrate-induced intestinal disorder in marine farmed Atlantic salmon, Salmo salar is associated with alterations in gut microbiota.

The aquaculture industry has made substantial progress in reducing the fishmeal content of feeds for carnivorous species, driven by demand for improved sustainability and reduced cost. Soybean protein concentrate (SPC) is an attractive replacement for fishmeal, but intestinal disorders have been reported in Atlantic salmon (Salmo salar) fed these diets at high seawater temperatures, with preliminary evidence suggesting SPC induces these disorders by altering the intestinal microbiota. We compared the intestinal microbiota of marine-farmed S. salar fed experimental diets with varying levels of SPC in mid- and late-summer. Terminal restriction fragment length polymorphism (T-RFLP) and 16S rRNA clone library analysis revealed the microbiota adherent to the intestinal tract of salmon is complex at the population level, but simple and highly variable at the individual level. Temporal changes were observed with the bacterial diversity increasing in the intestinal tract in late summer. A Verrucomicrobia was the most frequently observed ribotype in early summer, whilst an Aliivibrio was the most frequently observed ribotype in late summer. Feeding SPC to salmon increased the bacterial diversity of the intestinal tract and resulted in the presence of bacteria not normally associated with marine fish (Escherichia and Propionibacterium). These diet-induced changes to the intestinal-microbiome could be ameliorated by inclusion of a prebiotic (mannan-oligosaccharide or MOS) to the diet. None of the experimental diets induced inflammation of the intestine as assessed by histopathology and expression of inflammatory cytokines. Our results support the "dysbiosis" hypothesis that SPC adversely affects the intestinal microbiota of Atlantic salmon.

Effects of multiple daily genistein treatments on delayed alternation and a differential reinforcement of low rates of responding task in middle-aged rats.

The use of extracts that are highly enriched in phytoestrogens, such as genistein, has become popular to promote various aspects of healthy aging, including maintenance of cognitive function. These compounds are promoted to menopausal women as safe, natural alternatives to traditional estrogen therapies, yet their safety and efficacy are poorly understood. Previous research in our lab found that once daily oral treatment of ovariectomized female Long-Evans (LE) rats with the soy phytoestrogen, genistein resulted in subtle deficits in performance on cognitive tasks assessing working memory and response inhibition/timing ability. The present study further modeled exposure of the menopausal woman to genistein by treating 14-month old ovariectomized female LE rats three times daily at a dose of genistein resulting in serum concentrations similar to those that could be achieved in humans consuming either a commercially available soy isoflavone supplement or a diet high in these phytoestrogens. Genistein (3.4 mg/kg) or sucrose control pellets were orally administered to animals daily, 30 min before behavioral testing, and again both 4 and 8 h after the first treatment. The test battery consisted of a delayed spatial alternation task (DSA) that tested working memory and a differential reinforcement of low rates of responding (DRL) task that tested inhibitory control/timing. Genistein treatment impaired DSA performance relative to sucrose controls. Performance on the DRL task was largely unaffected by genistein treatment. Although the impairment measured on DSA was less pronounced than that we have previously reported following chronic treatment with 17ß-estradiol, the pattern of the deficit was very similar to that observed with 17ß-estradiol.

NTP-CERHR expert panel report on the developmental toxicity of soy infant formula.

Soy infant formula contains soy protein isolates and is fed to infants as a supplement to or replacement for human milk or cow milk. Soy protein isolates contains estrogenic isoflavones (phytoestrogens) that occur naturally in some legumes, especially soybeans. Phytoestrogens are nonsteroidal, estrogenic compounds. In plants, nearly all phytoestrogens are bound to sugar molecules and these phytoestrogen-sugar complexes are not generally considered hormonally active. Phytoestrogens are found in many food products in addition to soy infant formula, especially soy-based foods such as tofu, soy milk, and in some over-the-counter dietary supplements. Soy infant formula was selected for National Toxicology Program (NTP) evaluation because of (1) the availability of large number of developmental toxicity studies in laboratory animals exposed to the isoflavones found in soy infant formula (namely, genistein) or other soy products, as well as few studies on human infants fed soy infant formula, (2) the availability of information on exposures in infants fed soy infant formula, and (3) public concern for effects on infant or child development. On October 2, 2008 (73 FR 57360), the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) announced its intention to conduct an updated review of soy infant formula to complete a previous evaluation that was initiated in 2005. Both the current and previous evaluations relied on expert panels to assist the NTP in developing its conclusions on the potential developmental effects associated with the use of soy infant formula, presented in the NTP Brief on Soy Infant Formula. The initial expert panel met on March 15 to 17, 2006, to reach conclusions on the potential developmental and reproductive toxicities of soy infant formula and its predominant isoflavone constituent genistein. The expert panel reports were released for public comment on May 5, 2006 (71 FR 28368). On November 8, 2006 (71 FR 65537), CERHR staff released draft NTP Briefs on Genistein and Soy Formula that provided the NTP's interpretation of the potential for genistein and soy infant formula to cause adverse reproductive and/or developmental effects in exposed humans. However, CERHR did not complete these evaluations, finalize the briefs, or issue NTP Monographs on these substances based on this initial evaluation. Between 2006 and 2009, a substantial number of new publications related to human exposure or reproductive and/or developmental toxicity were published for these substances. Thus, CERHR determined that updated evaluations of genistein and soy infant formula were needed. However, the current evaluation focuses only on soy infant formula and the potential developmental toxicity of its major isoflavone components, e.g. genistein, daidzein (and estrogenic metabolite, equol), and glycitein. This updated evaluation does not include an assessment on the potential reproductive toxicity of genistein following exposures during adulthood as was carried out in the 2006 evaluation. CERHR narrowed the scope of the evaluation because the assessment of reproductive effects of genistein following exposure to adults was not considered relevant to the consideration of soy infant formula use in infants during the 2006 evaluation. To obtain updated information about soy infant formula for the CERHR evaluation, the PubMed (Medline) database was searched from February 2006 to August 2009 with genistein/genistin, daidzein/daidzin, glycitein/glycitin, equol, soy, and other relevant keywords. References were also identified from the bibliographies of published literature. The updated expert panel report represents the efforts of a 14-member panel of government and nongovernment scientists, and was prepared with assistance from NTP staff. The finalized report, released on January 15, 2010 (75 FR 2545), reflects consideration of public comments received on a draft report that was released on October 19, 2009, for public comment and discussions that occurred at a public meeting of the expert panel held December 16 to 18, 2009 (74 FR 53509). The finalized report presents conclusions on (1) the strength of scientific evidence that soy infant formula or its isoflavone constituents are developmental toxicants based on data from in vitro, animal, or human studies; (2) the extent of exposures in infants fed soy infant formula; (3) the assessment of the scientific evidence that adverse developmental health effects may be associated with such exposures; and (4) knowledge gaps that will help establish research and testing priorities to reduce uncertainties and increase confidence in future evaluations. The Expert Panel expressed minimal concern for adverse developmental effects in infants fed soy infant formula. This level of concern represents a "2" on the five-level scale of concern used by the NTP that ranges from negligible concern ("1") to serious concern ("5"). The Expert Panel Report on Soy Infant Formula was considered extensively by NTP staff in preparing the 2010 NTP Brief on Soy Infant Formula, which represents the NTP's opinion on the potential for exposure to soy infant formula to cause adverse developmental effects in humans. The NTP concurred with the expert panel that there is minimal concern for adverse effects on development in infants who consume soy infant formula. This conclusion was based on information about soy infant formula provided in the expert panel report, public comments received during the course of the expert panel evaluation, additional scientific information made available since the expert panel meeting, and peer reviewer critiques of the draft NTP Brief by the NTP Board of Scientific Counselors (BSC) on May 10, 2010 (Meeting materials are available at http://ntp.niehs.nih.gov/go/9741.). The BSC voted in favor of the minimal concern conclusion with 7 yes votes, 3 no votes, and 0 abstentions. One member thought that the conclusion should be negligible concern and two members thought that the level of concern should be higher than minimal concern. The NTP's response to the May 10, 2010 review ("peer-review report") is available on the NTP website at http://ntp.niehs.nih.gov/go/9741. The monograph includes the NTP Brief on Soy Infant Formula as well as the entire final Expert Panel Report on Soy Infant Formula. Public comments received as part of the NTP's evaluation of soy infant formula and other background materials are available at http://cerhr.niehs.nih.gov/evals/index.html.

Inner ear biocompatibility of lipid nanocapsules after round window membrane application.

Nanoparticle-mediated drug delivery represents the future in terms of treating inner ear diseases. Lipid core nanocapsules (LNCs), 50 nm in size, were shown to pass though the round window membrane (RWM) and reached the spiral ganglion cells and nerve fibers, among other cell types in the inner ear. The present study aimed to evaluate the toxicity of the LNCs in vitro and in vivo, utilizing intact round window membrane delivery in rats. The primary cochlear cells and mouse fibroblast cells treated with LNCs displayed dosage dependant toxicity. In vivo study showed that administration of LNCs did not cause hearing loss, nanoparticle application-related cell death, or morphological changes in the inner ear, at up to 28 days of observation. The cochlear neural elements, such as synaptophysin, ribbon synapses, and S-100, were not affected by the administration of LNCs. However, expression of neurofilament-200 decreased in SGCs and in cochlear nerve in osseous spiral lamina canal after LNC delivery, a phenomenon that requires further investigation. LNCs are potential vectors for the delivery of drugs to the inner ear.

Soybean toxin (SBTX), a protein from soybeans that inhibits the life cycle of plant and human pathogenic fungi.

Soybean toxin (SBTX) is a 44 kDa glycoprotein that is lethal to mice (LD(50) = 5.6 mg/kg). This study reports the toxicity of SBTX on pathogenic fungi and yeasts and the mechanism of its action. SBTX inhibited spore germination of Aspergillus niger and Penicillium herguei and was toxic to Candida albicans, Candida parapsilosis, Kluyveromyces marxiannus , Pichia membranifaciens, and Saccharomyces cerevisiae. In addition, SBTX hampered the growth of C. albicans and K. marxiannus and inhibited the glucose-stimulated acidification of the incubation medium by S. cerevisiae, suggesting that SBTX interferes with intracellular proton transport to the external medium. Moreover, SBTX caused cell-wall disruption, condensation/shrinkage of cytosol, pseudohyphae formation, and P. membranifaciens and C. parapsilosis cell death. SBTX is toxic to fungi at concentrations far below the dose lethal to mice and has potential in the design of new antifungal drugs or in the development of transgenic crops resistant to pathogens.

Soy, phyto-oestrogens and male reproductive function: a review.

There is growing interest in the possible health threat posed by the effects of endocrine disruptors on reproduction. Soy and soy-derived products contain isoflavones that mimic the actions of oestrogens and may exert adverse effects on male fertility. The purpose of this review was to examine the evidence regarding the potential detrimental effects of soy and phyto-oestrogens on male reproductive function and fertility in humans and animals. Overall, there are some indications that phyto-oestrogens, alone or in combination with other endocrine disruptors, may alter reproductive hormones, spermatogenesis, sperm capacitation and fertility. However, these results must be interpreted with care, as a result of the paucity of human studies and as numerous reports did not reveal any adverse effects on male reproductive physiology. Further investigation is needed before a firm conclusion can be drawn. In the meantime, caution would suggest that perinatal phyto-oestrogen exposure, such as that found in infants feeding on soy-based formula, should be avoided.