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Vallejo, CA, United States

Lansita J.A.,ToxStrategies Inc. | Mounho-Zamora B.,Century Inc.
Current Pain and Headache Reports | Year: 2015

Monoclonal antibodies (mAbs) represent a class of biotechnology-derived therapeutics for use in the treatment of various disease indications such as oncology, autoimmune, cardiovascular, and metabolic disorders. Monoclonal antibodies are immunoglobulin (Ig) proteins engineered to bind to specific antigens with high specificity. The concepts reviewed in this paper include 1) the regulatory procedures and guidelines that apply to mAbs, 2) the types of toxicology studies applicable to mAbs, and 3) the scientific challenges, such as the selection of a relevant animal species and the development of anti-drug antibodies, that can arise due to the unique properties of mAbs. © 2015, Springer Science+Business Media New York. Source


Mahadevan B.,Abbott Laboratories | Thorsrud B.A.,MPI Research Inc. | Brorby G.P.,ToxStrategies Inc. | Ferguson H.E.,Abbott Laboratories
Food and Chemical Toxicology | Year: 2014

Octenyl succinic anhydride (OSA)-modified starch functions as both an emulsifier and emulsion stabilizer in foods, and is intended for use in infant formula, follow-on formula, and formulae for special medical purposes. These formulae predominantly include extensively hydrolyzed protein or free amino acids, rather than intact protein, which otherwise would provide emulsifying functionality. The study objectives were to evaluate (1) the safety of OSA-modified starch after three weeks of administration to neonatal farm piglets, beginning 2. days after birth and (2) the impact of OSA-modified starch on piglet growth. OSA-modified starch was added to formula at concentrations of 2, 4, and 20. g/L. The vehicle control, low-dose, and mid-dose diets were supplemented with Amioca™ Powder to balance the nutritional profiles of all formulations. There were no test article-related effects of any diet containing OSA-modified starch on piglet growth and development (clinical observations, body weight, feed consumption), or clinical pathology parameters (hematology, clinical chemistry, coagulation, urinalysis). In addition, there were no adverse effects at terminal necropsy (macro- and microscopic pathology evaluations). Therefore, dietary exposure to OSA-modified starch at concentrations up to 20. g/L was well tolerated by neonatal farm piglets and did not result in adverse health effects or impact piglet growth. © 2014 Elsevier Ltd. Source


Berman D.W.,Aeolus Inc. | Brorby G.P.,ToxStrategies Inc. | Sheehan P.J.,Exponent, Inc. | Bogen K.T.,Exponent, Inc. | Holm S.E.,Georgia Pacific LLC
Annals of Occupational Hygiene | Year: 2012

An ongoing research effort designed to reconstruct the character of historical exposures associated with use of chrysotile-containing joint compounds naturally raised questions concerning how the character (e.g. particle size distributions) of dusts generated from use of recreated materials compares to dusts from similar materials manufactured historically. This also provided an opportunity to further explore the relative degree that the characteristics of dusts generated from a bulk material are mediated by the properties of the bulk material versus the mechanical processes applied to the bulk material by which the dust is generated. In the current study, the characteristics of dusts generated from a recreated ready mix and recreated dry mix were compared to each other, to dusts from a historical dry mix, and to dusts from the commercial chrysotile fiber (JM 7RF3) used in the recreated materials. The effect of sanding on the character of dusts generated from these materials was also explored. Dusts from the dry materials studied were generated and captured for analysis in a dust generator-elutriator. The recreated and historical joint compounds were also prepared, applied to drywall, and sanded inside sealed bags so that the particles produced from sanding could be introduced into the elutriator and captured for analysis. Comparisons of fiber size distributions in dusts from these materials suggest that dust from commercial fiber is different from dusts generated from the joint compounds, which are mixtures, and the differences persist whether the materials are sanded or not. Differences were also observed between sanded recreated ready mix and either the recreated dry mix or a historical dry mix, again whether sanded or not. In all cases, however, such differences disappeared when variances obtained from surrogate data were used to better represent the 'irreducible variation' of these materials. Even using the smaller study-specific variances, no differences were observed between the recreated dry mix and the historical dry mix, indicating that chrysotile-containing joint compounds can be recreated using historical formulations such that the characteristics of the modern material reasonably mimic those of a corresponding historical material. Similarly, no significant differences were observed between dusts from sanded and unsanded versions of similar materials, suggesting (as in previous studies) that the characteristics of asbestos-containing dusts are mediated primarily by the properties of the bulk material from which they are derived. © 2012 The Author. Source


Cullen J.M.,North Carolina State University | Ward J.M.,Global VetPathology | Thompson C.M.,ToxStrategies Inc.
Toxicologic Pathology | Year: 2016

Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response. © The Author(s) 2015. Source


Urban J.D.,ToxStrategies Inc. | Carakostas M.C.,ToxStrategies Inc. | Taylor S.L.,University of Nebraska - Lincoln
Food and Chemical Toxicology | Year: 2015

Steviol glycoside sweeteners are extracted from the plant Stevia rebaudiana (Bertoni), a member of the Asteraceae (Compositae) family. Many plants from this family can induce hypersensitivity reactions via multiple routes of exposure (e.g., ragweed, goldenrod, chrysanthemum, echinacea, chamomile, lettuce, sunflower and chicory). Based on this common taxonomy, some popular media reports and resources have issued food warnings alleging the potential for stevia allergy. To determine if such allergy warnings are warranted on stevia-based sweeteners, a comprehensive literature search was conducted to identify all available data related to allergic responses following the consumption of stevia extracts or highly purified steviol glycosides. Hypersensitivity reactions to stevia in any form are rare. The few cases documented in the peer-reviewed literature were reported prior to the introduction of high-purity products to the market in 2008 when many global regulatory authorities began to affirm the safety of steviol glycosides. Neither stevia manufacturers nor food allergy networks have reported significant numbers of any adverse events related to ingestion of stevia-based sweeteners, and there have been no reports of stevia-related allergy in the literature since 2008. Therefore, there is little substantiated scientific evidence to support warning statements to consumers about allergy to highly purified stevia extracts. © 2014 Elsevier Ltd. Source

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