Download or read book NTP Developmental and Reproductive Toxicity Technical Report on the Modified One generation Study of 2 Ethylhexyl P Methoxycinnamate CASRN 5466 77 3 Administered in Feed to Sprague Dawley Hsd Sprague Dawley r SD r Rats with Prenatal Reproductive Performance and Subchronic Assessments in F1 sOffspring written by and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 2-Ethylhexyl p-methoxycinnamate (EHMC), also known as octinoxate and octyl methoxycinnamate, is a common component of sunscreens, cosmetics, and personal care products. Mechanistic screening studies have purported that EHMC, and its metabolites, are capable of activating the estrogen receptor to varying degrees. The objective of this study was to characterize the potential for EHMC to adversely affect any phase of rat development, maturation, and ability to reproduce. The potential for EHMC to induce subchronic toxicity in the F1\sgeneration, to adversely affect the ability of the F1\sgeneration to reproduce viable F2\soffspring, and to adversely affect the F2\sembryo-fetal development was assessed in Sprague Dawley (Hsd:Sprague Dawley(r) SD(r)) rats administered EHMC in 5K96 feed, a diet low in phytoestrogens, using the National Toxicology Program modified one-generation (MOG) study design. The dietary route of administration was selected to approximate continual exposure in group-housed animals. EHMC exposure via the diet, rather than topical application, was selected for this study to sustain internal exposure; if applied topically, the internal dose would have been influenced by intra- and interanimal grooming behavior. Exposure concentration selection for the MOG study was based on a dose range-finding study in which time-mated rats were exposed to 0, 2,250, 5,000, 10,000, or 20,000\sppm EHMC in the diet from gestation day (GD)\s6 through lactation day (LD)\s28. Dams exposed to 20,000\sppm displayed significantly decreased mean body weights on GD\s21 and body weight gain from GD\s6 through GD\s21. Dams exposed to 20,000\sppm displayed lower live litter size, and pups in this group displayed significantly decreased PND\s1 weights and lower postnatal viability resulting in the group being removed from study on postnatal day (PND)\s14. Pup body weights of the 10,000\sppm group were also lower than those in the control group. Therefore, exposure concentrations of 0, 1,000, 3,000, and 6,000\sppm were selected for the subsequent MOG study. Test article consumption was exposure concentration-proportional. EHMC intake for F0\sfemales in the 2,250, 5,000, 10,000, and 20,000\sppm groups, based on feed consumption and dietary concentrations for GD\s6 through GD\s21, was approximately 161, 365, 714, and 1,841\smg EHMC/kg body weight/day (mg/kg/day), respectively; from LD\s1 through LD\s14, EHMC intake was approximately 410, 925, and 1,615\smg/kg/day for the 2,250, 5,000, and 10,000\sppm groups, respectively.MODIFIED ONE-GENERATION STUDY: F0\sexposure began on GD\s6 and was continual. At weaning on PND\s28, F1\soffspring were assigned to the reproductive performance (up to 2/sex/litter, when available), prenatal (1/sex/litter), or subchronic cohort (1/sex from 10 litters). Upon sexual maturity, F1\smating and pregnancy indices were evaluated. In the prenatal cohort, F2\sprenatal development (litter size, fetal weight, and morphology) was assessed on GD\s21. In the reproductive performance cohort, littering indices, F2\sviability, and growth were assessed until PND\s28. The likelihood of identifying potential EHMC-induced adverse effects (similarity and magnitude thereof) at any phase of growth or development was increased by examining related endpoints and multiple pups within a litter throughout life, across cohorts, and across generations. EHMC did not induce overt F0\sor F1\smaternal toxicity or affect mating or pregnancy indices. Dam feed consumption and body weights were slightly lower during lactation in the 6,000\sppm group. EHMC exposure at 6,000\sppm was associated with significantly decreased F1\sand F2\spreweaning mean body weights, with an onset at approximately PND\s13, consistent with the beginning of pup feed consumption. Significantly decreased F1\spreweaning mean body weights were observed in males and females exposed to 3,000 or 6,000\sppm, whereas only F2\smale and female preweaning mean body weights of the 6,000\sppm group were significantly decreased relative to their respective control groups. Although mean body weight gains of males (PND\s28-105) and females (PND\s28-\s91) in all EHMC-exposed groups were similar to those of the respective control groups, postweaning F1\smale and female mean body weights of the 6,000\sppm group were significantly decreased by 5%-14% relative to the respective control animals. Both male and female mean body weights of the 3,000\sppm groups were significantly decreased by approximately 5% on PND\s28, but by PND\s56, their mean body weights were comparable to those of the control groups. Lower F1\spostweaning body weights were not associated with concurrent lower feed consumption. EHMC intake by F0\sfemales in the 1,000, 3,000, and 6,000\sppm EHMC groups, based on feed consumption and dietary concentrations from GD\s6 through GD\s21, was approximately 70, 207, and 419\smg/kg/day, respectively; from LD\s1 through LD\s13, EHMC intake was approximately 161, 475, and 920\smg/kg/day, respectively. EHMC intake by the F1\sgeneration postweaning (PND\s28 through PND\s91) in the 1,000, 3,000, and 6,000\sppm groups was approximately 80, 242, and 491\smg/kg/day (males) and 87, 263, and 528\smg/kg/day (females), respectively. EHMC intake by the adult F1\sfemales in the 1,000, 3,000, and 6,000\sppm groups was approximately 73, 220, and 435\smg/kg/day (GD\s0 through GD\s21) and 139, 418, and 842\smg/kg/day (LD\s1 through LD\s13), respectively. EHMC exposure did not alter anogenital distance or areola/nipple retention. The timing of weaning weight-adjusted vaginal opening (VO) and balanopreputial separation (BPS) was significantly delayed by approximately 2.1\sdays and 2.2\sdays, respectively, in the 6,000\sppm group. F1\srats exposed to 6,000\sppm EHMC displayed slightly more time in estrus. Reproductive performance (fertility and fecundity) was not affected by EHMC exposure. The numbers of live fetuses and pups were not affected. EHMC exposure was not associated with any effects on fetal weight or the incidences of external, visceral, or skeletal malformations. The 6,000\sppm group did exhibit a higher combined fetal incidence of lumbar\s1 rudimentary rib variants (approximately 10% versus 4% in the control group). In the subchronic cohort, no gross findings, changes in organ weights, or histopathological findings were attributed to EHMC exposure. CONCLUSIONS: Under the conditions of this modified one-generation (MOG) study, there was no evidence of reproductive toxicity of 2-ethylhexyl p-methoxycinnamate (EHMC) in Hsd:Sprague Dawley(r) SD(r) rats at exposure concentrations of 1,000, 3,000, or 6,000\sppm. Mating and littering were not affected significantly by EHMC exposure. Under the conditions of this MOG study, there was equivocal evidence of developmental toxicity of EHMC in Hsd:Sprague Dawley(r) SD(r) rats based on the observed postnatal effects on body weight that showed some indication of recovery by study end, delays in postnatal day\s28-adjusted vaginal opening and balanopreputial separation, which could have been influenced by the apparent transient effects on body weight, and time in estrus was slightly longer in EHMC-exposed females relative to that of the control group. No other signals consistent with alterations in estrogenic, androgenic, or antiandrogenic action were observed. EHMC exposure did not induce any specific fetal malformations.SYNONYMS: octinoxate; ethylhexyl methoxycinnamate; octyl methoxycinnamate; 2-propenoic acid, 3-(4-methoxyphenyl)-, 2-ethylhexyl ester; 2-ethylhexyl 3-(4-methoxyphenyl)prop-2-enoate.
Download or read book National Toxicology Program Annual Report for Fiscal Year written by National Toxicology Program (U.S.) and published by . This book was released on 1992 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Alternative Toxicological Methods written by Harry Salem and published by CRC Press. This book was released on 2003-03-26 with total page 616 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bringing together the recent and relevant contributions of over 125 scientists from industry, government, and academia in North America and Western Europe, Alternative Toxicological Methods explores the development and validation of replacement, reduction, and refinement alternatives (the 3Rs) to animal testing. Internationally recognized scientist
Download or read book Validation of Alternative Methods for Toxicity Testing written by Chantra Eskes and published by Springer. This book was released on 2016-09-26 with total page 407 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides information on best practices and new thinking regarding the validation of alternative methods for toxicity testing. It covers the validation of experimental and computational methods and integrated approaches to testing and assessment. Validation strategies are discussed for methods employing the latest technologies such as tissue-on-a-chip systems, stem cells and transcriptomics, and for methods derived from pathway-based concepts in toxicology. Validation of Alternative Methods for Toxicity Testing is divided into two sections, in the first, practical insights are given on the state-of-the-art and on approaches that have resulted in successfully validated and accepted alternative methods. The second section focuses on the evolution of validation principles and practice that are necessary to ensure fit-for-purpose validation that has the greatest impact on international regulatory acceptance of alternative methods. In this context validation needs to keep pace with the considerable scientific advancements being made in toxicology, the availability of sophisticated tools and techniques that can be applied in a variety of ways, and the increasing societal and regulatory demands for better safety assessment. This book will be a useful resource for scientists in the field of toxicology, both from industry and academia, developing new test methods, strategies or techniques, as well as Governmental and regulatory authorities interested in understanding the principles and practicalities of validation of alternative methods for toxicity testing.
Download or read book Adverse Effects of Engineered Nanomaterials written by Bengt Fadeel and published by Academic Press. This book was released on 2012-01-27 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: An essential reference that discusses occupational exposure and the adverse health effects of engineered nanomaterials and highlights current and future biomedical applications of these nanomaterials in relation to nanosafety.
Download or read book Translational Toxicology written by Claude L. Hughes and published by Humana Press. This book was released on 2016-03-23 with total page 380 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bringing together a distinguished interdisciplinary team of contributors, this volume provides a comprehensive exploration of translational toxicology—a systematic approach to developing therapeutic interventions that can protect against, mitigate, or reverse the effects of exposures. In particular, the book addresses modes of action and biomarkers, developmental risks of exposures, and potential translational toxicology therapeutics. The result is a compelling application of developmental toxicology in a new therapeutic discipline that is destined to become part of standard medical practice. Translational Toxicology: Defining a New Therapeutic Discipline is an essential text for regulatory authorities, scientists, and physicians who are concerned with environmental exposures, public health, nutrition, and pharmaceutical research and development. Basic science, epidemiological, and clinical investigators will also find this book a significant resource.
Download or read book Significant New Use Rules on Certain Chemical Substances Us Environmental Protection Agency Regulation Epa 2018 Edition written by Law Library and published by Createspace Independent Publishing Platform. This book was released on 2018-09 with total page 68 pages. Available in PDF, EPUB and Kindle. Book excerpt: Significant New Use - Rules on Certain Chemical Substances (US Environmental Protection Agency Regulation) (EPA) (2018 Edition) The Law Library presents the complete text of the Significant New Use - Rules on Certain Chemical Substances (US Environmental Protection Agency Regulation) (EPA) (2018 Edition). Updated as of May 29, 2018 EPA is promulgating significant new use rules (SNURs) under the Toxic Substances Control Act (TSCA) for 57 chemical substances which were the subject of premanufacture notices (PMNs). The applicable review periods for the PMNs submitted for these 57 chemical substances all ended prior to June 22, 2016 (i.e., the date on which President Obama signed into law the Frank R. Lautenberg Chemical Safety for the 21st Century Act which amends TSCA). Thirty-four of these chemical substances are subject to TSCA section 5(e) consent orders issued by EPA. This action requires persons who intend to manufacture (defined by statute to include import) or process any of these 57 chemical substances for an activity that is designated as a significant new use by this rule to notify EPA at least 90 days before commencing that activity. The required notification initiates EPA's evaluation of the intended use within the applicable review period. Manufacture and processing for the significant new use is unable to commence until EPA has conducted a review of the notice, made an appropriate determination on the notice, and take such actions as are required with that determination. This book contains: - The complete text of the Significant New Use - Rules on Certain Chemical Substances (US Environmental Protection Agency Regulation) (EPA) (2018 Edition) - A table of contents with the page number of each section
Download or read book Chemical Status Report written by and published by . This book was released on 1992 with total page 36 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Toxicity Testing of Chemicals written by United States. Congress. Senate. Committee on Environment and Public Works. Subcommittee on Toxic Substances and Environmental Oversight and published by . This book was released on 1984 with total page 134 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Atlas of Histology of the Juvenile Rat written by George A Parker and published by Academic Press. This book was released on 2016-05-04 with total page 464 pages. Available in PDF, EPUB and Kindle. Book excerpt: Atlas of Histology of the Juvenile Rat should be of interest to toxicologic pathologists, toxicologists, and other biological scientists who are interested in the histomorphology of juvenile rats. For several decades the laboratory rat has been used extensively in nonclinical toxicology studies designed to detect potential human toxicity of drugs, agrochemicals, industrial chemicals, and environmental hazards. These studies traditionally have involved young adult rats that are 8-10 weeks of age as studies are started. It is becoming increasingly apparent that children and young animals may have different responses to drug/chemical exposures, therefore, regulatory agencies are emphasizing toxicology studies in juvenile animals. While the histologic features of organs from young adult and aged laboratory rats are well known, less is known about the histologic features of organs from juvenile rats. Final histologic maturity of many organs is achieved postnatally, thus immature histologic features must be distinguished from chemical- or drug-related effects. While this postnatal organ development is known to exist as a general concept, detailed information regarding postnatal histologic development is not readily available. The Atlas includes organs that are typically sampled in nonclinical toxicology studies and presents the histologic features at weekly intervals, starting at birth and extending through postnatal day 42. Written and edited by highly experienced, board-certified toxicologic pathologists Includes more than 700 high-resolution microscopic images from organs that are typically examined in safety assessment toxicology studies Detailed figure legends and chapter narratives present the salient features of each organ at each time interval Figures are available for further study via Elsevier’s Virtual Microscope, which allows viewing of microscopic images at higher magnification Valuable resource for toxicologic pathologists who are confronted with interpretation of lesions in juvenile rats in situations where age-matched concurrent controls are not available for comparison, e.g., with unscheduled decedents Figures are available for further study on ScienceDirect with Virtual Microscope, which allows viewing of microscopic images at higher magnification
