Second primary uterine malignancies after radiation therapy for cervical cancer.

PURPOSE: Radiation exposure has long been established as a risk factor for cancer development. The purpose of this study is to assess the risk of uterine malignancy in patients previously treated for cervical cancer with radiation therapy. METHODS: A population-based cohort of 9092 patients diagnosed with cervical cancer who did not undergo surgery and received radiation therapy between 1973 and 2008 was identified from the Surveillance, Epidemiology and End Results Program database (SEER 9). Patients in this cohort who developed endometrial cancer after treatment of cervical cancer were identified. 55,140 patients with endometrial cancer were also identified. The distribution of the different histologic types of endometrial cancer was determined for each of these cohorts. RESULTS: 54 patients (0.6%) were diagnosed with an endometrial cancer more than 12 months after diagnosis of cervical cancer. The average latency to endometrial cancer diagnosis was 160 months, with a range of 14-374 months. The average age of cervical cancer diagnosis was 52 years and the average age at subsequent endometrial cancer diagnosis was 66 years. Only 40% of the endometrial cancers diagnosed following treatment of cervical cancer were endometrioid. The majority were clear-cell adenocarcinomas (42%), 9% were carcinosarcomas and 5.5% were leiomyosarcomas. Of the 55,140 endometrial cancer patients in the database, a vast majority were endometrioid adenocarcinomas (91%), and only 2.3% clear-cell adenocarcinoma, 2.3% carcinosarcoma and 0.5% leiomyosarcoma. The difference in histologic type distribution between these two cohorts is highly significant (p < 0.01). CONCLUSION: A small proportion of women who receive radiation for cervical cancer go on to develop endometrial cancer. These are predominantly of the more aggressive histologic types when compared to primary endometrial cancers. The latency from cervical cancer diagnosis to endometrial cancer diagnosis is over a decade. In a patient who still has a uterus after receiving pelvic radiation, vaginal bleeding should be investigated.

The Effect of Hospital Volume on Breast Cancer Mortality.

OBJECTIVE: The aim of this study was to determine whether hospital volume was associated with mortality in breast cancer, and what thresholds of case volume impacted survival. BACKGROUND: Prior literature has demonstrated improved survival with treatment at high volume centers among less common cancers requiring technically complex surgery. METHODS: All adults (18 to 90 years) with stages 0-III unilateral breast cancer diagnosed from 2004 to 2012 were identified from the American College of Surgeons National Cancer Data Base (NCDB). A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital volume and overall survival, after adjusting for measured covariates. Intergroup comparisons of patient and treatment characteristics were conducted with X and analysis of variance (ANOVA). The log-rank test was used to test survival differences between groups. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) associated with each volume group. RESULTS: One million sixty-four thousand two hundred and fifty-one patients met inclusion criteria. The median age of the sample was 60 (interquartile range 50 to 70). Hospitals were categorized into 3 groups using restricted cubic spline analysis: low-volume (<148 cases/year), moderate-volume (148 to 298 cases/year), and high-volume (>298 cases/year). Treatment at high volume centers was associated with an 11% reduction in overall mortality for all patients (HR 0.89); those with stage 0-I, ER+/PR+ or ER+/PR- breast cancers derived the greatest benefit. CONCLUSIONS: Treatment at high volume centers is associated with improved survival for breast cancer patients regardless of stage. High case volume could serve as a proxy for the institutional infrastructure required to deliver complex multidisciplinary breast cancer treatment.

Potential of Lactobacillus curvatus LFC1 to produce slits in Cheddar cheese.

Defects in Cheddar cheese resulting from undesired gas production are a sporadic problem that results in significant financial losses in the cheese industry. In this study, we evaluate the potential of a facultatively heterofermentative lactobacilli, Lactobacillus curvatus LFC1, to produce slits, a gas related defect in Cheddar cheese. The addition of Lb. curvatus LFC1 to cheese milk at log 3 CFU/ml resulted in the development of small slits during the first month of ripening. Chemical analyses indicated that the LFC1 containing cheeses had less galactose and higher levels of lactate and acetate than the control cheeses. The composition the cheese microbiota was examined through a combination of two culture independent approaches, 16S rRNA marker gene sequencing and automated ribosomal intergenic spacer analysis; the results indicated that no known gas producers were present and that high levels of LFC1 was the only significant difference between the cheese microbiotas. A ripening cheese model system was utilized to examine the metabolism of LFC1 under conditions similar to those present in cheeses that exhibited the slit defect. The combined cheese and model system results indicate that when Lb. curvatus LFC1 was added to the cheese milk at log 3 CFU/ml it metabolized galactose to lactate, acetate, and CO2. For production of sufficient CO2 to result in the formation of slits there needs to be sufficient galactose and Lb. curvatus LFC1 present in the cheese matrix. To our knowledge, facultatively heterofermentative lactobacilli have not previously been demonstrated to result in gas-related cheese defects.

Effect of various high-pressure treatments on the properties of reduced-fat Cheddar cheese.

A major problem with reduced-fat cheese is the difficulty in attaining the characteristic flavor and texture of typical full-fat versions. Some previous studies have suggested that high hydrostatic pressure (HHP) can accelerate the ripening of full-fat cheeses. Our objective was to investigate the effect of HHP on reduced-fat (~7.3% fat) Cheddar cheese, with the goal of improving its flavor and texture. We used a central composite rotatable design with response surface methodology to study the effect of pressure and holding time on the rheological, physical, chemical, and microbial characteristics of reduced-fat Cheddar cheese. A 2-level factorial experimental design was chosen to study the effects of the independent variables (pressure and holding time). Pressures were varied from around 50 to 400 MPa and holding times ranged from 2.5 to 19.5 min. High pressure was applied 1 wk after cheese manufacture, and analyses were performed at 2 wk, and 1, 3, and 6 mo. The insoluble calcium content as a percentage of total Ca in cheeses were not affected by pressure treatment. Pressure applications ≥ 225 MPa resulted in softer cheese texture during ripening. Pressures ≥ 225 MPa increased melt, and resulted in higher maximum loss tangent values at 2 wk. Pressure treatment had a greater effect on cheese microbial and textural properties than holding time. High-pressure-treated cheeses also had higher pH values than the control. We did not observe any significant difference in rates of proteolysis between treatments. In conclusion, holding times of around 5 min and pressures of ≥ 225 MPa could potentially be used to improve the excessively firm texture of reduced-fat cheese.

Induction of DNA synthesis in cultured rat hepatocytes through stimulation of alpha 1 adrenoreceptor by norepinephrine.

Addition of norepinephrine to primary cultures of adult rat hepatocytes stimulates the incorporation of [3H]thymidine in a dose-dependent manner. This effect has been observed in serum-free medium containing epidermal growth factor and insulin. Stimulation of DNA synthesis by norepinephrine was strongly antagonized by the alpha 1-adrenergic antagonist prazosin but not by an alpha 2 antagonist or by a beta-adrenergic blocker. The beta agonist isoproterenol did not stimulate significant DNA synthesis. These results indicate that catecholamines interact with the alpha 1 adrenoreceptor to stimulate DNA synthesis in hepatocytes. Since alpha 1 receptors are present in most cells, this receptor may be important in cell growth regulation.

The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor.

The fms-like tyrosine kinase (Flt) is a transmembrane receptor in the tyrosine kinase family. Expression of flt complementary DNA in COS cells conferred specific, high-affinity binding of vascular endothelial growth factor, also known as vascular permeability factor (VEGF-VPF), a factor that induces vascular permeability when injected in the guinea pig skin and stimulates endothelial cell proliferation. Expression of Flt in Xenopus laevis oocytes caused the oocytes to release calcium in response to VEGF-VPF. These findings show that flt encodes a receptor for VEGF-VPF.

Control of hepatocyte replication by two serum factors.

Serum proteins from hepatectomized or control rats were separated by gel permeation chromatography and assayed for stimulation of hepatocyte proliferation in primary cultures of hepatocytes. Two peaks of activity were seen in the areas of large (greater than 120,000) and small (less than 3,000) molecular weight. These activities are different from insulin, epidermal growth factor, or vasopressin and are empirically termed hepatopoietin A and B, respectively. The two activities interact in a synergistic manner to stimulate hepatocyte proliferation at rates comparable to that of the whole serum.

Introduction of a Ha-ras oncogene into rat liver epithelial cells and parenchymal hepatocytes confers resistance to the growth inhibitory effects of TGF-beta.

Growth of rat liver epithelial cells (RLEC) and primary cultures of parenchymal hepatocytes is potently inhibited by TGF-beta. Transfection of a mutated Ha-ras oncogene, but not a human c-myc oncogene, into RLEC resulted in cell lines resistant to growth inhibition by TGF-beta under anchorage-dependent conditions. Infection of primary rat hepatocyte cultures with v-Ha-ras yielded a cell line likewise insensitive to inhibition by TGF-beta. Binding of [125I]TGF-beta to Ha-ras-transfected RLEC was reduced relative to control or c-myc-transfected cells. These data suggest that activation of a Ha-ras oncogene in epithelial cells may result in escape from negative growth control and hence be a critical step during carcinogenesis. However, although Ha-ras induced resistance to growth inhibition by TGF-beta under anchorage-dependent conditions, TGF-beta inhibited the spontaneous growth in soft agar of all cell lines containing the Ha-ras oncogene. This may reflect an alteration in regulation of extracellular matrix proteins and related enzymes responsible for anchorage-independent growth.

Conditional transformation of rat embryo fibroblast cells by a cyclin D1-cdk4 fusion gene.

Cyclin D1 gene overexpression is a frequent event in a number of human cancers. These observations have led to the suggestion that cyclin D1 alterations might play a role in the etiology of cancer. This possibility is supported by the finding that transfection of mammalian cells with cyclin D1 can accelerate progression through the G1 phase of the cell cycle. Moreover, cyclin D1 can function as an oncogene by cooperating with activated Ha-ras to transform primary rat embryo fibroblasts (REFs). In addition, cyclin D1 transgenics develop hyperplasia and neoplasia of the thymus and mammary gland. We have constructed a novel fusion gene consisting of full-length human cyclin D1 and cdk4 genes. This fusion gene was expressed in insect cells and the fusion protein was shown to be enzymatically active. The fusion gene was expressed in mammalian cells under the control of tet-repressor. This fusion gene immortalized primary REFs, and cooperated with activated Ha-ras to transform primary REFs, in terms of anchorage-independent growth in vitro and formation of tumors in vivo. Utilizing a tet-regulated gene expression system, we have shown that proliferation of stably transfected primary REFs in vitro and in vivo is dependent on the continued expression of the cyclin D1-cdk4 fusion gene. These cell lines could be useful in the discovery of novel cancer therapeutics to modulate cyclin D1.cdk4 activity.

The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA.

Vascular endothelial growth factor (VEGF) was recently identified as a secreted, direct-acting mitogen specific for vascular endothelial cells and capable of stimulating angiogenesis in vivo. Molecular cloning revealed multiple forms of VEGF, apparently arising from alternative splicing of its RNA transcript. We have examined various human cDNA libraries by the polymerase chain reaction technique and discovered a fourth molecular form, VEGF206. This form contains a 41-amino acid insertion relative to the most abundant form, VEGF165, and includes the highly basic 24-amino acid insertion found in VEGF189. Southern blot analysis revealed that a single gene encoded these various forms, and nucleic acid sequence analysis of a portion of the VEGF gene revealed an intron/exon structure compatible with alternative splicing of RNA as a mechanism for their generation. Transient transfection of human embryonic kidney 293 cells showed that, like VEGF189, VEGF206 was predominately cell-associated and only very poorly secreted despite the presence of the signal peptide identical to that found in VEGF121 and VEGF165, both of which are efficiently exported from the cell. Vascular permeability activity was detected in the medium of 293 cells transfected with all four forms of VEGF; however, endothelial cell mitogenic activity was apparent only with VEGF121 and VEGF165. Thus, alternative splicing of VEGF RNA can produce four polypeptides with strikingly different secretion patterns, which suggests multiple physiological roles for this family of proteins.

Effect of heat treatment of milk on activation of Bacillus spores.

The quality and shelf life of fluid milk products are dependent on the amount and type of microorganisms present following pasteurization. This study evaluated the effects of different pasteurization processes on the microbial populations in fluid milk. The objective was to determine whether certain pasteurization processes lead to an increase in the amount of bacteria present in pasteurized milk by activating Bacillus spores. Samples of raw milk were collected on the day of arrival at the dairy plant. The samples were pasteurized at 63 degrees C for 30 min (low temperature, long time), 72 degrees C for 15 s (high temperature, short time), 76 degrees C for 15 s, and 82 degrees C for 30 min. The pasteurized samples were then stored at 6 and 10 degrees C for 14 days. The samples were analyzed for standard plate count and Bacillus count immediately after pasteurization and after 14 days of storage. Pasteurization of milk at 72 and 76 degrees C significantly (P < 0.05) increased the amount of Bacillus spore activation over that of 63 degrees C. There was no detection of Bacillus in initial samples pasteurized at 82 degrees C for 30 min, but Bacillus was present in samples after storage for 14 days, indicating that injury and recovery time preceded growth. The majority of isolates were characterized as Bacillus mycoides and not Bacillus cereus, suggesting that this organism might be more a cause of sweet curdling of fluid milk than previously reported.

Borderline tumors of the ovary: correlation of frozen and permanent histopathologic diagnosis.

OBJECTIVE: To evaluate the correlation between the diagnosis of borderline tumor of the ovary by frozen and permanent pathology. METHODS: All pathology reports with diagnoses of borderline tumor of the ovary between 1980 and 1998 at Massachusetts General Hospital were reviewed. Univariate and multivariable logistic regression models were constructed for patient age, tumor size, histology, presence of bilateral or extraovarian disease, and concurrent diagnosis of endometriosis or endosalpingiosis. RESULTS: We reviewed 140 cases. The average age of patients was 52.3 years. Eighty tumors were serous, 47 mucinous, 11 mixed, and two endometrioid. The mean diameter overall was 13.7 cm (range 1-70 cm), 10.2 cm for serous, and 20.1 cm for mucinous. Diagnoses of borderline tumors by frozen and permanent pathology were consistent in 60% of cases. Frozen section interpreted a benign lesion as malignant (overdiagnosed) in 10.7% of cases, and interpreted a malignant lesion as benign (underdiagnosed) in 29.3%. No variable was a significant predicator of overdiagnosis. In univariate analysis, underdiagnosis was more likely for other types of tumors than serous (P <.001), tumors larger than 20 cm (P =.039), and tumors confined to the ovaries (P =. 009). When all variables were included in a multiple regression model, only histology was a significant predictor of underdiagnosis (P =.039). CONCLUSION: Frozen or permanent pathology reports of diagnoses of borderline tumor were consistent 60% of the time, whereas the positive predictive value of borderline by frozen section was 89.3%. Tumors other than serous are more likely to be misinterpreted.

A Food Variety Index for Toddlers (VIT): development and application.

OBJECTIVE: To develop a variety index based on the Food Guide Pyramid that is specific to toddlers and is indicative of dietary adequacy. DESIGN: Subjects' mothers were assigned randomly to two in-home interviews with a registered dietitian at four possible collection periods: 24, 28, 32, or 36 months. Three days of dietary information were collected at each period. A Variety Index for Toddlers (VIT) was developed to assess variety within and among food groups based on the number of servings from the food groups in the Food Guide Pyramid. SUBJECTS: White children aged 24 to 36 months (n = 124) and their mothers who were participants in an ongoing longitudinal study. STATISTICAL ANALYSES: Descriptive statistical procedures were performed on VIT scores. Mean adequacy ratio (MAR) scores were calculated for all subjects and compared with VIT scores. RESULTS: Bread group scores were consistently the highest of the individual food groups (mean score = 0.94 to 0.96 on the 0.0 to 1.0 scale); the vegetable and meat groups were generally the lowest (mean score = 0.68 to 0.73 and 0.73 to 0.76, respectively). Mean VIT scores (an average of the five food group scores) over the four collection periods ranged from 0.79 +/- 0.14 to 0.81 +/- 0.15; a score of 1.00 represented intake of at least the minimum number of recommended servings from each food group. VIT scores were strongly correlated to the MAR score of nutrient adequacy (r = +.74, P < .01). APPLICATIONS: The VIT can provide a numeric description of dietary variety specific to toddlers. VIT scores can be compared with other characteristics of children, and this index has the potential to be adapted for use with other age groups and populations.

Longitudinal study of nutrient and food intakes of infants aged 2 to 24 months.

OBJECTIVE: To determine the nutrient and food intakes of healthy, white infants from families of middle and upper socioeconomic status and to compare intakes to current recommendations. DESIGN: Using an incomplete random block design, we interviewed 98 mother-infant pairs longitudinally when infants were 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 months old. Data obtained included 24-hour dietary recalls, usual food intake, and food likes and dislikes. SETTING: Interviews were conducted in the mother's home by registered dietitians. Subjects resided in two urban areas of Tennessee. SUBJECTS: Of the original 98 subjects, 94 completed the 2-year study. RESULTS: Mean energy and nutrient intakes generally met or exceeded the Recommended Dietary Allowance (RDA). Exceptions were zinc and vitamin D, which were each below 100% of the RDA at 9 of the 10 data points, and vitamin E, which was below the RDA in the infants' second year. Fat intake decreased from more than 40% of energy in the first 6 months to 30% to 32% from 10 to 24 months. One third of the infants drank reduced-fat milks at 12 months and more than half drank them at 24 months. Although infants ate a variety of foods, vegetables often were the least favorite foods. A variety of dairy products provided calcium for the infant but lacked vitamin D. CONCLUSIONS: Several nutritional issues about infant feeding before 2 years of age arose. Low intakes of zinc, vitamin D, and vitamin E were observed. In the second year, low fat intake, use of reduced-fat milks, and dislike of vegetables were areas of concern.

Longitudinal study of nutrient and food intakes of white preschool children aged 24 to 60 months.

OBJECTIVE: To determine nutrient and food intakes of 72 white preschool children primarily from families of middle and upper socioeconomic status and to compare children's nutrient intakes with current recommendations. DESIGN: Six in-home interviews were conducted with mothers when children were 24 to 60 months old; at each time mothers provided 3 days of dietary information on the child. Children and mothers independently provided information on the child's favorite and least favorite foods at 42 and 54 months. SUBJECTS: Preschool children (24 to 60 months old) participating in a longitudinal study. STATISTICAL ANALYSES: Mean nutrient intakes were compared with the most recent Recommended Dietary Allowances/Adequate Intakes. Differences over time were tested with repeated-measures analysis of variance; gender differences were determined with t tests. Food frequencies (i.e., percentage of children consuming specific foods) were determined from dietary recalls and food records. Dietary variety was assessed with the Variety Index for Toddlers or the Variety Index for Children. RESULTS: Means were consistently less than the RDA/AI for energy, zinc, folate, and vitamins D and E. Energy, carbohydrate, and fat intakes were highest (P < or = .01) at 60 months. Boys consumed more (P < or = .05) protein (10 g), calcium (197 mg), magnesium (35 mg), and pantothenic acid (0.8 mg) at 60 months than did girls. Foods most commonly eaten were fruit drink, carbonated beverages, 2% milk, and french fries. The vegetable group consistently had the lowest variety scores; vegetables also dominated least favorite foods lists. APPLICATIONS: Parents need to be encouraged to include more sources of zinc, folate, vitamin E, and vitamin D in children's diets. Parents should also encourage their children to eat more vegetables, zinc- and folate-fortified cereals, lean red meats, seafood, vegetable oils, and low-fat milk.

Ecological toxicology and human health effects of heptachlor.

The chlorinated cyclodiene heptachlor was registered in 1952 as an agricultural and domestic insecticide. By early 1984, registration for all purposes, except subterranean termite control and for limited use in the control of fire ants, had been cancelled. This restriction of use arose primarily from concerns over the environmental persistance and bioaccumulation potential of the organochlorine pesticides. Currently, sale of heptachlor has been voluntarily suspended over questions about its carcinogenic potential, and the absence of safe and effective application methods. As a persistent organochlorine pesticide, heptachlor residues are detected in all components of the environment. In historical use, heptachlor was directly applied to terrestrial systems, while air and water were secondarily contaminated via volatilization and land run-off, respectively. Within each environmental compartment, heptachlor undergoes a variety of metabolic and abiotic transformations. In vivo studies indicate that heptachlor epoxide is the predominant metabolite, formed as a product of the mixed-function oxidase system, while 1-hydroxychlordene is the major soil metabolite. For quantification, heptachlor and its metabolites are extracted from air, soil and sediment, water, or biological materials using various organic solvents and analyzed by gas chromatography or thin-layer chromatography. Residue reports comprise most of the literature concerning the effects of heptachlor on the biota. In many such reports, toxic effects cannot be conclusively attributed to heptachlor exposure. Toxicity to organisms seems more dependent on acute exposure, while the chronic effects of low level exposure to heptachlor are poorly defined. Maximal terrestrial residues coincide with temporal and spatial proximity to application; peak residues in aquatic systems on the other hand, correlate to periods of maximum run-off. The lipophilic nature of both heptachlor and heptachlor epoxide results in the potential for significant bioaccumulation in all lipid-type compartments in the environment. The toxic effects of heptachlor are not specific for any one organ system. The liver and the central nervous system are most significantly affected by heptachlor, although effects can also be seen in the reproductive, hematopoietic, immune, and renal systems. An important consideration is the relation of relevant environmental exposure levels to toxicity. The concentrations necessary to elicit results in laboratory experiments do not translate directly to the same results upon environmental exposure, nor do experimental laboratory animal models absolutely equate with native-state organisms or with humans.(ABSTRACT TRUNCATED AT 400 WORDS)

Quality of life in advanced ovarian cancer: identifying specific concerns.

PURPOSE: To identify issues affecting the quality of life (QoL) in women receiving palliative therapy for ovarian cancer. METHODS: Twenty women with advanced recurrent ovarian cancer were interviewed to establish what issues affect QoL. All patients were receiving palliative chemotherapy or other palliative therapy in the department of Gynecologic Oncology at the Massachusetts General Hospital, and were felt to have a life expectancy of 1 year or less by best clinical estimate. RESULTS: Twenty patients with an average age of 56.7 years participated. Psychosocial issues were more common than physical ones, and patients were more likely to mention issues that positively impact on QoL rather than those with a negative effect. Most patients noted that a sense of hope, enhanced appreciation for day to day life, and a strong support system had a significantly positive effect on QoL. Issues negatively impacting QoL included fear of their disease (90%) and concern for family and friends (100%), particularly children. Most common physical symptoms impacting QoL included fatigue (100%) and anorexia (55%). CONCLUSIONS: Little research has been done into QoL issues for ovarian cancer patients receiving palliative care. Available QoL studies tend to focus on the physical aspects of a disease or its treatment. This pilot study suggests that women with advanced, recurrent ovarian cancer feel that psychosocial issues play a greater role in determining QoL than do physical issues. Further QoL studies for these patients should include assessment of psychosocial realms. This information can then be used to design interventions to improve QoL.

Early events in the regulation of hepatocyte DNA synthesis: the role of alpha-adrenergic stimulation.

The role of adrenergic agents in DNA synthesis was investigated in two models of stimulated hepatocyte growth: in vitro primary serum-free cultures of adult parenchymal hepatocytes, and in vivo liver regeneration after two-thirds partial hepatectomy. In both systems the alpha 1-adrenergic receptor appeared to be involved in mediating stimulatory effects. In primary hepatocyte cultures norepinephrine acted via this receptor to enhance the DNA synthesis stimulated by epidermal growth factor (EGF), and heterologously downregulated EGF receptors. In liver regeneration the administration of an alpha 1 blocking agent interfered with the first wave of regenerative DNA synthesis, and this effect was preceded by an elevation in EGF receptor number. Measurements of plasma catcholamines demonstrated that elevated levels of norepinephrine and epinephrine were in circulation within 2 h after partial hepatectomy. Surgical hepatic sympathectomy also interfered with early liver regeneration, suggesting that locally delivered adrenergic agents are important to initiation of DNA synthesis. These data suggest that stimulation at the alpha 1-adrenergic receptor is among the early signals for liver regeneration and that heterologous regulation of EGF receptors, similar to that observed in vitro, may be a part of the regenerative response.

Zebrafish developmental screening of the ToxCast™ Phase I chemical library.

Zebrafish (Danio rerio) is an emerging toxicity screening model for both human health and ecology. As part of the Computational Toxicology Research Program of the U.S. EPA, the toxicity of the 309 ToxCast™ Phase I chemicals was assessed using a zebrafish screen for developmental toxicity. All exposures were by immersion from 6-8 h post fertilization (hpf) to 5 days post fertilization (dpf); nominal concentration range of 1 nM-80 µM. On 6 dpf larvae were assessed for death and overt structural defects. Results revealed that the majority (62%) of chemicals were toxic to the developing zebrafish; both toxicity incidence and potency was correlated with chemical class and hydrophobicity (logP); and inter-and intra-plate replicates showed good agreement. The zebrafish embryo screen, by providing an integrated model of the developing vertebrate, compliments the ToxCast assay portfolio and has the potential to provide information relative to overt and organismal toxicity.