Scale-free dynamics of COVID-19 in a Brazilian city.

A common basis to address the dynamics of directly transmitted infectious diseases, such as COVID-19, are compartmental (or SIR) models. SIR models typically assume homogenous population mixing, a simplification that is convenient but unrealistic. Here we validate an existing model of a scale-free fractal infection process using high-resolution data on COVID-19 spread in São Caetano, Brazil. We find that transmission can be described by a network in which each infectious individual has a small number of susceptible contacts, of the order of 2-5. This model parameter correlated tightly with physical distancing measured by mobile phone data, such that in periods of greater distancing the model recovered a lower average number of contacts, and vice versa. We show that the SIR model is a special case of our scale-free fractal process model in which the parameter that reflects population structure is set at unity, indicating homogeneous mixing. Our more general framework better explained the dynamics of COVID-19 in São Caetano, used fewer parameters than a standard SIR model and accounted for geographically localized clusters of disease. Our model requires further validation in other locations and with other directly transmitted infectious agents.

The effect of denudation and injection timing in the reproductive outcomes of ICSI cycles: new insights into the risk of in vitro oocyte ageing.

STUDY QUESTION: Does the time elapsed between oocyte pick-up (OPU) and denudation or injection affect the probability of achieving a live birth (LB) in ICSI cycles? SUMMARY ANSWER: Prolonged oocyte culture before denudation (>4 h) was associated with an increase in clinical pregnancy (CP), LB and cumulative LB (CLB) rates when compared with earlier denudation timings. WHAT IS KNOWN ALREADY: Oocyte maturation is a complex and dynamic process involving structural and biochemical modifications in the cell necessary to support fertilization and early embryo development. While meiotic competence is easily identifiable by the presence of an extruded first polar body, cytoplasmic maturation cannot be assessed microscopically. Culturing oocytes with their surrounding cumulus cells (CCs) prior to ICSI can enhance the completion of in vitro cytoplasmic maturation; conversely, prolonged culture may induce cell degeneration. The optimal culture intervals prior to oocyte denudation and/or injection have not yet been established and may prove relevant for the improvement of ICSI reproductive outcomes. STUDY DESIGN, SIZE, DURATION: This is a single-centre retrospective cohort analysis of 1378 ICSI cycles performed between January 2005 and October 2018. Data were categorized according to: (i) the time interval between OPU and denudation (<3 h, 3-4 h and ≥4 h), (ii) the time interval between denudation and ICSI (<1.5 h, 1.5-2 h, ≥2 h) and (iii) the time interval between OPU and ICSI (<5 h, 5-6 h and ≥6 h). The effect of these timings on fertilization, CP, LB and CLB rates were compared. The culture intervals between different procedures were dependent exclusively on laboratory workload. PARTICIPANTS/MATERIALS, SETTING, METHODS: ICSI cycles performed in women younger than 40 years old using autologous gametes with at least one metaphase II injected oocyte were included. The effect of oocyte culture duration prior to denudation and injection of the oocytes was compared using multivariable regression accounting for potential confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE: Fertilization and oocyte damage rate after ICSI was found to be independent of the time interval to denudation (<3 h, 3-4 h and ≥4 h) and/or injection (<5 h, 5-6 h and ≥6 h). Extending oocyte culture before denudation significantly improved CP (29.5%, 42.7% and 50.6%, respectively), LB (25.1%, 34.4% and 40.7%, respectively) and CLB rates (26.0%, 36.1% and 42.2%, respectively), particularly if the time interval was at least 4 h. Additionally, LB (31.7%, 35.8% and 27.4%, respectively) and CLB rates (34.2%, 36.6% and 27.7%, respectively) were also dependent on the time from OPU to injection. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective nature and potential unmeasured confounding cannot be excluded. Furthermore, the effect of even shorter or longer periods of culture before denudation and/or injection were not evaluated and should not be extrapolated from these results. WIDER IMPLICATIONS OF THE FINDINGS: Our findings propose new evidence of a previously unrecognized protective effect of the CCs-oocyte interactions in human ART, raising the question of a possible downstream effect in embryogenesis which significantly affects LB rates. Additionally, this is the first study to suggest a negative effect of further extending culture before ICSI on LB and CLB rates, thus potentially allowing for the narrowing of an optimal ICSI time interval. Simple strategies such as the establishment of more effective time frames to perform these procedures and adjusting laboratory practice may prove beneficial, ultimately improving ICSI reproductive outcomes. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Responses of monogenean species to variations in abiotic parameters in tilapiculture.

Fish farming is becoming an increasingly popular agricultural activity, and water quality in these environments is a major concern. Fish parasites, such as monogeneans, respond to changes in abiotic conditions, either with an increase or decrease in population. This study aimed to identify gill monogeneans and analyse their relationships with abiotic factors during the ontogenetic development of Nile tilapia over the fish culture cycle in Mato Grosso do Sul, Brazil. Fish were sampled monthly for eight months, and a total of 200 fish were collected. The physical and chemical water parameters were measured and correlated with the abundance of each monogenean species. Over the fish culture cycle, the physical and chemical parameters fluctuated, and the water quality decreased. The parasites found included Cichlidogyrus tilapiae, Cichlidogyrus thurstonae, Cichlidogyrus sclerosus, Cichlidogyrus halli and Scutogyrus longicornis. The abundances of all species showed significant differences during ontogenetic development (body size) and C. tilapiae, C. sclerosus, C. thurstonae and S. longicornis were correlated with changes in abiotic conditions. However, C. halli was not significantly correlated with any of the evaluated physical or chemical parameters. Understanding how different monogenean species respond to changes in the physical and chemical parameters of water during a production cycle can prevent peaks in abundance and subsequent sanitary problems.

Use of Paliperidone Palmitate Throughout a Schizoaffective Disorder Patient's Gestation Period.

Introduction: Paliperidone palmitate treatment of schizophrenia or schizoaffective disorder is effective and well tolerated, but there is almost no data on its safety during pregnancy. Case report: An analysis is made of the safety and tolerability of paliperidone palmitate treatment throughout the gestation period in a 34-year-old patient diagnosed with schizoaffective disorder. Discussion: Paliperidone palmitate treatment throughout the gestation period was safe and well tolerated by both mother and foetus, there being no malformations or other perinatal complications in the newborn to date.

Thyroid Function in Human Obesity: Underlying Mechanisms.

Obesity is associated with several metabolic and endocrine disorders; and changes in plasma concentrations, secretion patterns, and clearance of various hormones are observed in obese patients. In this context, recent research has shown that overweight can influence the function of the thyroid gland, usually leading to increased thyrotropin concentrations and changes in the ratio between the hormones triiodothyronine and thyroxine, though within the normal range. The etiology of these changes is still unclear; however, several mechanisms have been proposed including the adaptive process to increase energy expenditure, hyperleptinemia, changes in the activity of deiodinases, the presence of thyroid hormones resistance, chronic low-grade inflammation, and insulin resistance. Although the clinical implications have not been clarified, studies suggest that these changes in the thyroid function of obese individuals may contribute to the worsening of metabolic complications and the development of diseases in the thyroid gland.

[Implications of chilean legal framework in teen pregnancy prevention: conflict and insecurity in health professionals]. / Implicancias del marco legal chileno en la prevención del embarazo adolescente: conflicto e inseguridad en los profesionales de la salud.

BACKGROUND: Teenage pregnancy is a psychosocial and multifactorial problem described as a lack of exercise of rights in sexual and reproductive health. There are important aspects in the doctor-patient relationship and confidentiality that directly affect the continuity and quality of care. There are controversies in the laws relating to the provision of contraception and confidentiality, and those that protect the sexual indemnity, especially in adolescents under 14 years. AIM: To describe the implications of the legal framework for professional midwives in the care of adolescents younger than 14 years in sexual and reproductive health. MATERIAL AND METHODS: In-depth interviews were conducted to 13 female and 2 male midwives working at Primary Health Care Centers in the Metropolitan Region. RESULTS: The attention of adolescents younger than 14 years in sexual and reproductive health involves medical-legal issues for health professionals. All professionals recognize that mandatory reporting sexual activity is a complex situation. All professionals notify pregnancies. In relation to the delivery of contraception, clinical care is problematic since professionals should take shelter from a legal standpoint. CONCLUSIONS: The medical-legal context of pregnant women under 14 years of age care generates a context of uncertainty and fear for professionals and becomes a source of conflict and insecurity in the exercise of the profession.

Methylmalonic aciduria cblB type: characterization of two novel mutations and mitochondrial dysfunction studies.

Methylmalonic aciduria (MMA) cblB type is caused by mutations in the MMAB gene, which codes for the enzyme adenosine triphosphate (ATP): cobalamin adenosyltransferase (ATR). This study reports differences in the metabolic and disease outcomes of two pairs of siblings with MMA cblB type, respectively harbouring the novel changes p.His183Leu/p.Arg190dup (P1 and P2) and the previously described mutations p.Ile96Thr/p.Ser174fs (P3 and P4). Expression analysis showed p.His183Leu and p.Arg190dup to be destabilizing mutations. Both were associated with reduced ATR stability and a shorter half-life than wild-type ATR. Analysis of several parameters related to oxidative stress and mitochondrial function showed an increase in reactive oxygen species (ROS) content, a decrease in mitochondrial respiration and changes in mitochondria morphology and structure in patient-derived fibroblasts compared to control cells. The impairment in energy production and the presence of oxidative stress and fission of the mitochondrial reticulum suggested mitochondrial dysfunction in cblB patients' fibroblasts. The recovery of mitochondrial function should be a goal in efforts to improve the clinical outcome of MMA cblB type.

[(2R,3R)-3-(4-Nitro-phen-yl)aziridin-2-yl]methanol monohydrate.

The title monohydrate, C9H10N2O3·H2O, contains an aziridine ring including two contiguous stereocenters, both of which exhibit an R configuration. The methyl-hydroxy and nitro-phenyl groups are cis-disposed about the aziridine ring. The mean plane of the benzene ring is tilted to the aziridine ring by 66.65 (8)°. The nitro group is nearly coplanar with the benzene ring [dihedral angle = 2.5 (2)°]. In the crystal, the components are linked by N-H⋯O, O-H⋯N and O-H⋯O hydrogen bonds, generating supra-molecular layers parallel to (001).

Stratifying risk outcomes among adult COVID-19 inpatients with high flow oxygen: The R4 score.

BACKGROUND: High flow oxygen therapy (HFO) is a widely used intervention for pulmonary complications. Amid the coronavirus infectious disease 2019 (COVID-19) pandemic, HFO became a popular alternative to conventional oxygen supplementation therapies. Risk stratification tools have been repurposed -and new ones developed- to estimate outcome risks among COVID-19 patients. This study aims to provide a simple risk stratification system to predict invasive mechanical ventilation (IMV) or death among COVID-19 inpatients on HFO. METHODS: Among 529 adult inpatients with COVID-19 pneumonia, we selected unadjusted clinical risk factors for developing the composite endpoint of IMV or death. The risk for the primary outcome by each category was estimated using a Cox proportional hazards model. Bootstrapping was used to validate the results. RESULTS: Age above 62, eGFR under 60 ml/min, room air SpO2 ≤89 % upon admission, history of hypertension, history of diabetes, and any comorbidity (cancer, cardiovascular disease, COPD/ asthma, hypothyroidism, or autoimmune disease) were considered for the score. Each of the six criteria scored 1 point. The score was further simplified into 4 categories: 1) 0 criteria, 2) 1 criterion, 3) 2-3 criteria, and 4) ≥4 criteria. Taking the first category as the reference, risk estimates for the primary endpoint were HR; 2.94 [1.67 - 5.26], 4.08 [2.63 - 7.05], and 6.63 [3.74 - 11.77], respectively. In ROC analysis, the AUC for the model was 0.72. CONCLUSIONS: Our score uses simple criteria to estimate the risk for IMV or death among COVID-19 inpatients with HFO. Higher category reflects consistent increases in risk for the endpoint.

Lack of correlation between sealer penetration into dentinal tubules and sealability in nonbonded root fillings.

AIM: To determine the correlation between leakage and sealer penetration into dentinal tubule. METHODOLOGY: The root canal of 60 mandibular central incisor teeth were prepared and filled under standardized conditions. Teeth were placed into a device to assess glucose penetration using 15 psi pressure application. After 1 h, glucose concentrations in the lower chamber were measured using an enzymatic reaction. Each specimen was then sectioned horizontally at 3, 6 and 8 mm from the apex, and a standard metallographic preparation was performed. The coronally facing surface of each slice was examined in a high-resolution stereomicroscope and under Confocal Laser Scanning Microscope. For each slice, the external outline of the root canal, the internal circumference of the root canal walls and the areas along the canal walls where the sealer had penetrated into the dentinal tubules (sealer tags) were outlined and measured. Afterwards, the percentage of the sealer penetration in each section was calculated. The Spearman correlation test was used to verify the correlation between the variables studied (glucose leakage and sealer penetration into dentinal tubules). RESULTS: The means and standard deviations of glucose leakage were 0.744 g L(-1) (±0.5), and the percentage of the dentinal tubule sealer penetration varied between teeth from 5.6% to 42.21%, with an average of 13.7 ± 17.2%. The Spearman correlation test revealed no significant correlation between the two factors analysed (P = 0.082). The r(2) value was equal to 0.12. CONCLUSIONS: There was no significant correlation between sealability sealer penetration into dentinal tubules. The lack of correlation reported is of relevance as sealer penetration into dentinal tubules has been used as an advantageous property during the launch of new root filling materials and techniques.

Evaluation of anaerobic biodegradability of wastewater from tebuconazole manufacturing.

This study aimed to verify the biological anaerobic treatability of tebuconazole effluent manufacturing. For this purpose, two preliminary batch tests were performed using an 'anaerobic respirometer' adjusting the initial pH of the effluent at 7.0 and 8.0, respectively (first phase). In addition, two tests (second phase) were run using sequential batch anaerobic fermenters, the first operated at different hydraulic detention times (10 and 16.7 days) and the second with different initial dilutions of the effluent (5 and 20%). The chemical oxygen demand (COD) removal observed on the anaerobic respirometer tests was in the range of 66-81%. According to the preliminary batch tests an optimal value of initial COD concentration and amount of biomass was identified, which was considered for the fermenters start up. However, it was observed that the optimal relation provided by the respirometer test was not a good parameter of operational control for the fermenters due to the accumulation of inhibitory substances, which affected the microbial activity and took the system to collapse. The initial dilution of the effluent (5 and 20%) was essential for the stability of the anaerobic system, allowing COD removals above 74% during this study.

Unfolding of crumpled thin sheets.

Crumpled thin sheets are complex fractal structures whose physical properties are influenced by a hierarchy of ridges. In this paper, we report experiments that measure the stress-strain relation and show the coexistence of phases in the stretching of crumpled surfaces. The pull stress showed a change from a linear Hookean regime to a sublinear scaling with an exponent of 0.65±0.03, which is identified with the Hurst exponent of the crumpled sheets. The stress fluctuations are studied. The statistical distribution of force peaks is analyzed. It is shown that the unpacking of crumpled sheets is guided by a hierarchical order of ridges.

Genome-wide DNA methylation profiling in anorexia nervosa discordant identical twins.

Up until now, no study has looked specifically at epigenomic landscapes throughout twin samples, discordant for Anorexia nervosa (AN). Our goal was to find evidence to confirm the hypothesis that epigenetic variations play a key role in the aetiology of AN. In this study, we quantified genome-wide patterns of DNA methylation using the Infinium Human DNA Methylation EPIC BeadChip array ("850 K") in DNA samples isolated from whole blood collected from a group of 7 monozygotic twin pairs discordant for AN. Results were then validated performing a genome-wide DNA methylation profiling using DNA extracted from whole blood of a group of non-family-related AN patients and a group of healthy controls. Our first analysis using the twin sample revealed 9 CpGs associated to a gene. The validation analysis showed two statistically significant CpGs with the rank regression method related to two genes associated to metabolic traits, PPP2R2C and CHST1. When doing beta regression, 6 of them showed statistically significant differences, including 3 CpGs associated to genes JAM3, UBAP2L and SYNJ2. Finally, the overall pattern of results shows genetic links to phenotypes which the literature has constantly related to AN, including metabolic and psychological traits. The genes PPP2R2C and CHST1 have both been linked to the metabolic traits type 2 diabetes through GWAS studies. The genes UBAP2L and SYNJ2 have been related to other psychiatric comorbidity.

Comparison of the root-end seal provided by bioceramic repair cements and White MTA.

AIM: To compare the ability of Ceramicrete, BioAggregate and white ProRoot MTA (mineral trioxide aggregate) to prevent glucose leakage through root-end fillings. METHODOLOGY: After root canal instrumentation, the apical 3 mm of maxillary incisors were resected and retropreparations, 3 mm in depth, were created with ultrasound. Root-end cavities were filled with the tested materials (15 roots per group). All roots were mounted in a double-chamber system to assess glucose penetration using 15 psi pressure application. After 1 h, glucose concentrations in the lower chamber were measured following an enzymatic reaction. Four roots were used as controls. One-way anova verified differences in glucose leakage between groups and Tukey test performed multiple comparisons. Significance was set at α = 5%. RESULTS: There was a significant difference between the three materials (anova, P < 0.05). Ceramicrete had significantly lower glucose penetration than BioAggregate (Tukey, P < 0.05). There was no difference between the two bioceramic cements and white MTA (P > 0.05). CONCLUSIONS: Both endodontic bioceramic repair cements displayed similar leakage results to white MTA when used as root-end fillings materials. Ceramicrete had significantly lower glucose penetration.

Presence of bacterial DNA in thrombotic material of patients with myocardial infarction.

Infectious agents have been suggested to be involved in etiopathogenesis of Acute Coronary Syndrome (ACS). However, the relationship between bacterial infection and acute myocardial infarction (AMI) has not yet been completely clarified. The objective of this study is to detect bacterial DNA in thrombotic material of patients with ACS with ST-segment elevation (STEMI) treated with Primary Percutaneous Coronary Intervention (PPCI). We studied 109 consecutive patients with STEMI, who underwent thrombus aspiration and arterial peripheral blood sampling. Testing for bacterial DNA was performed by probe-based real-time Polymerase Chain Reaction (PCR). 12 probes and primers were used for the detection of Aggregatibacter actinomycetemcomitans, Chlamydia pneumoniae, viridans group streptococci, Porphyromonas gingivalis, Fusobacterium nucleatum, Tannarella forsythia, Treponema denticola, Helycobacter pylori, Mycoplasma pneumoniae, Staphylococus aureus,  Prevotella intermedia and Streptococcus mutans. Thus, DNA of four species of bacteria was detected in 10 of the 109 patients studied. The most frequent species was viridans group streptococci (6 patients, 5.5%), followed by Staphylococus aureus (2 patients, 1.8%). Moreover, a patient had DNA of Porphyromonas gingivalis (0.9%); and another patient had DNA of Prevotella intermedia (0.9%). Bacterial DNA was not detected in peripheral blood of any of our patients. In conclusion, DNA of four species of endodontic and periodontal bacteria was detected in thrombotic material of 10 STEMI patients. Bacterial DNA was not detected in the peripheral blood of patients with bacterial DNA in their thrombotic material. Bacteria could be latently present in plaques and might play a role in plaque instability and thrombus formation leading to ACS.

Lower numbers of circulating Natural Killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease.

Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.

FibroScan used in street-based outreach for drug users is useful for hepatitis C virus screening and management: a prospective study.

Although hepatitis C virus (HCV) infection prevalence is high among drug users, they do not commonly receive regular care in academic centres. The aim of this prospective study was to assess the influence of FibroScan use on HCV screening and management in street-based outreach. From January 2006 to January 2007, all consecutive drug users were offered noninvasive evaluation of liver fibrosis with FibroScan. After FibroScan, parameters were recorded with a structured, face-to-face questionnaire by outreach workers. All 298 subjects accepted FibroScan evaluation drug use was--ever injected heroin (69%), ever snorted or injected cocaine (89%), current chronic alcohol abuse (44%). The median FibroScan score was 5.3 kPa. Before blood sampling, 34% of subjects reported HCV positivity. HCV positivity was found in 83 cases. All these subjects had positive HCV-RNA. Forty-five subjects agreed to meet a hepatologist. By multivariate analysis, never snorted cocaine, consumed alcohol < 21 drinks per week, duration of injected heroin > 7 years, and FibroScan > 7.1 kPa were significantly associated with HCV positivity. Thus in a street-based outreach service for drug users, the acceptance of FibroScan is excellent. FibroScan with a hospital-based physician may facilitate screening and management of drug users for HCV infection.

Evidence that the v-sis gene product transforms by interaction with the receptor for platelet-derived growth factor.

A scheme for partial purification of biologically active v-sis-coded protein from cells transformed with simian sarcoma virus (SSV) has made possible a functional comparison of the transforming protein with platelet-derived growth factor (PDGF). The SSV-transforming gene product is capable of specifically binding PDGF receptors, stimulating tyrosine phosphorylation of PDGF receptors, and inducing DNA synthesis in quiescent fibroblasts. Each of these activities was specifically inhibited by antibodies to different regions of the v-sis gene product. Moreover, viral infection of a variety of cell types revealed a strict correlation between those cells possessing PDGF receptors and those susceptible to transformation by SSV. These findings provide evidence that SSV-transforming activity is mediated by the interaction of a virus-coded mitogen with PDGF receptors.

Four Years' Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers.

Identification of very long-chain acyl-CoA dehydrogenase deficiency is possible in the expanded newborn screening (NBS) due to the increase in tetradecenoylcarnitine (C14:1) and in the C14:1/C2, C14:1/C16, C14:1/C12:1 ratios detected in dried blood spots. Nevertheless, different confirmatory tests must be performed to confirm the final diagnosis. We have revised the NBS results and the results of the confirmatory tests (plasma acylcarnitine profiles, molecular findings, and lymphocytes VLCAD activity) for 36 cases detected in three Spanish NBS centers during 4 years, correlating these with the clinical outcome and treatment. Our aim was to distinguish unambiguously true cases from disease carriers in order to obtain useful diagnostic information for clinicians that can be applied in the follow-up of neonates identified by NBS.Increases in C14:1 and of the different ratios, the presence of two pathogenic mutations, and deficient enzyme activity in lymphocytes (<12% of the intra-assay control) identified 12 true-positive cases. These cases were given nutritional therapy and all of them are asymptomatic, except one. Seventeen individuals were considered disease carriers based on the mild increase in plasma C14:1, in conjunction with the presence of only one mutation and/or intermediate residual activity (18-57%). In addition, seven cases were classified as false positives, with normal biochemical parameters and no mutations in the exonic region of ACADVL. All these carriers and the false positive cases remained asymptomatic. The combined evaluation of the acylcarnitine profiles, genetic results, and residual enzyme activities have proven useful to definitively classify individuals with suspected VLCAD deficiency into true-positive cases and carriers, and to decide which cases need treatment.

Lack of in vivo embryotoxic and genotoxic activities of orally administered stem bark aqueous extract of Mangifera indica L. (Vimang).

Mango (Mangifera indica L.) stem bark aqueous extract (MSBE) is a new natural product with antioxidant, anti-inflammatory and immunomodulatory effects known by the brand name of its formulations as Vimang. Previously, the oral toxicity studies of the extract showed a low toxicity potential up to 2000 mg/kg. This work reports the results about teratogenic and genotoxicologic studies of MSBE. For embryotoxicity study, MSBE (20, 200, or 2000 mg/kg/day) was given to Sprague-Dawley rats by gavage on days 6-15 of gestation. For genotoxicity, MSBE was administered three times during 48 h to NMRI mice. Cyclophosphamide (50 mg/kg) was used as a positive control. No maternal or developmental toxicities were observed when the rats were killed on day 20th. The maternal body-weight gain was not affected. No dose-related effects were observed in implantations, fetal viability or external fetal development. Skeletal and visceral development was similar among fetuses from all groups. No genotoxicity was observed in bone marrow erythrocytes and liver cells after administration. MSBE appears to be neither embryotoxic nor genotoxic as measured by bone marrow cytogenetics in rodents.