Birth Defects Research Part B: Developmental and Reproductive Toxicology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Relevance Weighting of Tier 1 Endocrine Screening Endpoints by Rank Order
Weight of evidence (WoE) approaches are recommended for interpreting various toxicological data, but few systematic and transparent procedures exist. A hypothesis‐based WoE framework was recently published focusing on the U.S. EPA's Tier 1 Endocrine Screening Battery (ESB) as an example. The framework recommends weighting each experimental endpoint according to its relevance for deciding eight hypotheses addressed by the ESB. Here we present detailed rationale for weighting the ESB endpoints according to three rank ordered categories and an interpretive process for using the rankings to reach WoE determinations. Rank 1 w...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - February 7, 2014 Category: Perinatology & Neonatology Authors: Christopher J. Borgert, Leah D. Stuchal, Ellen M. Mihaich, Richard A. Becker, Karin S. Bentley, John M. Brausch, Katie Coady, David R. Geter, Elliot Gordon, Patrick D. Guiney, Frederick Hess, Catherine M. Holmes, Matthew J. LeBaron, Steve Levine, Sue Mart Tags: Original Article Source Type: research

Key Lessons from Performance of the U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 Male and Female Pubertal Assays
This article uses the collective experience of three laboratories to provide information on pubertal assay conduct, interlaboratory reproducibility, endpoint redundancy, and data interpretation. The various criteria used to select the maximum tolerated dose are described. A comparison of historical control data across laboratories confirmed reasonably good interlaboratory reproducibility. With a reliance on apical endpoints, interpretation of pubertal assay effects as specifically endocrine‐mediated or secondary to other systemic effects can be problematic and mode of action may be difficult to discern. Across 21–23 da...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - February 7, 2014 Category: Perinatology & Neonatology Authors: Donald G. Stump, John C. O'Connor, Joseph M. Lewis, M. Sue Marty Tags: Original Article Source Type: research

Absence of Irreversible Effects of Aliskiren in Standard Juvenile Rat Toxicity Studies
CONCLUSIONSAll effects produced by aliskiren, including kidney effects, were reversible. Increased exposure in very young animals is considered to be the result of immature drug transporter systems. (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - February 1, 2014 Category: Perinatology & Neonatology Authors: David Beckman, Stephanie Barbeau, Lee Anne McLean, Jing‐He Yan, Peter Hoffmann Tags: Research Article Source Type: research

Issue Information
(Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - February 1, 2014 Category: Perinatology & Neonatology Tags: Issue Information Source Type: research

Ochratoxin A: Developmental and Reproductive Toxicity—An Overview
Ochratoxin A (OTA) is nephrotoxic, hepatotoxic, reprotoxic, embryotoxic, teratogenic, neurotoxic, immunotoxic, and carcinogenic for laboratory and farm animals. Male and female reproductive health has deteriorated in many countries during the last few decades. A number of toxins in environment are suspected to affect reproductive system in male and female. OTA is one of them. OTA has been found to be teratogenic in several animal models including rat, mouse, hamster, quail, and chick, with reduced birth weight and craniofacial abnormalities being the most common signs. The presence of OTA also results in congenital defects...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - January 6, 2014 Category: Perinatology & Neonatology Authors: Frantisek Malir, Vladimir Ostry, Annie Pfohl‐Leszkowicz, Eva Novotna Tags: Review Article Source Type: research

Interpreting Estrogen Screening Assays in the Context of Potency and Human Exposure Relative to Natural Exposures to Phytoestrogens
While the Environmental Protection Agency and the Organization for Economic Cooperation and Development have developed validated in vitro and in vivo screening assays to measure interaction of substances with estrogen, androgen and thyroid pathway components, to date, methods to contextualize such results in terms of potencies and actual human exposures are lacking. To place endocrine screening results in the context of potency and human exposure, we propose a method that entails (1) calculating a benchmark dose for a response measured in an endocrine screen; (2) estimating the human urinary concentration (biomonitoring eq...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - January 3, 2014 Category: Perinatology & Neonatology Authors: Richard A. Becker, Sean M. Hays, Christopher R. Kirman, Lesa L. Aylward, Kimberly Wise Tags: Research Article Source Type: research

Difference in Developmental Toxicity Among Structurally Similar N‐Phenylimide Herbicides in Rats and Rabbits
CONCLUSIONSThe difference in developmental toxicity in rats was striking among N‐phenylimide herbicides. The mechanism of action of developmental toxicity by S‐53482 should account for the compound‐specific difference as well as species difference between rats and rabbits. (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - January 3, 2014 Category: Perinatology & Neonatology Authors: Satoshi Kawamura, Terushige Kato, Noboru Kannan, Alan G. Fantel Tags: Original Article Source Type: research

Dihydroartemisinin (DHA) Treatment Causes an Arrest of Cell Division and Apoptosis in Rat Embryonic Erythroblasts in Whole Embryo Culture
Within 24 hr after oral administration of the antimalarial artesunate to rats on Day 10 or 11 postcoitum (pc), there is depletion of embryonic erythroblasts (EEbs), leading to embryo malformation and death. The proximate agent is dihydroartemisinin (DHA), the primary metabolite. We investigated the causes of EEb depletion by evaluating effects of DHA on EEbs in whole embryo culture (WEC). Rat embryos cultured starting on Day 9 pc were treated with 1 or 7 μM DHA for 24 hr starting after 19 hr of culture (∼Day 10 pc) and for 2 to 12 hr starting after 43 hr of culture (∼Day 11 pc). DHA effects indicating the dep...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - January 3, 2014 Category: Perinatology & Neonatology Authors: Lorraine M. Posobiec, Robert L. Clark, Paul B. Bushdid, Susan B. Laffan, Kai‐Fen Wang, Tacey E. K. White Tags: Research Article Source Type: research

Placental Transfer of Fc‐Containing Biopharmaceuticals across Species, an Industry Survey Analysis
CONCLUSIONSEmbryonic (before the end of organogenesis) exposure was assessed in one molecule each in rabbit, rat, and mouse, but detectable levels were present only in rodents. In rodents, fetal levels remained relatively constant from gestation day (GD) 16 and 17 until the end of gestation, while maternal levels decreased or remained constant in rat and decreased in mice. In rabbits, following a last dose on GD 19, fetal levels increased markedly in late gestation while maternal levels decreased. In the cynomolgus monkey, fetal levels increased substantially from GD 50 to 100 and were maintained relatively constant throu...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - January 3, 2014 Category: Perinatology & Neonatology Authors: Christopher J. Bowman, William J. Breslin, Anu V. Connor, Pauline L. Martin, Graeme J. Moffat, Lakshmi Sivaraman, M. Belen Tornesi, Simon Chivers Tags: Research Article Source Type: research

Genetic Association Analyses of Nitric Oxide Synthase Genes and Neural Tube Defects Vary by Phenotype
Neural tube defects (NTDs) are caused by improper neural tube closure during the early stages of embryonic development. NTDs are hypothesized to have a complex genetic origin and numerous candidate genes have been proposed. The nitric oxide synthase 3 (NOS3) G594T polymorphism has been implicated in risk for spina bifida, and interactions between that single nucleotide polymorphism (SNP) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have also been observed. To evaluate other genetic variation in the NO pathway in the development of NTDs, we examined all three NOS genes: NOS1, NOS2, and NOS3. Using ...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 9, 2013 Category: Perinatology & Neonatology Authors: Karen L. Soldano, Melanie E. Garrett, Heidi L. Cope, J. Michael Rusnak, Nathen J. Ellis, Kaitlyn L. Dunlap, Marcy C. Speer, Simon G. Gregory, Allison E. Ashley‐Koch Tags: Original Article Source Type: research

Assessment of a Nonsteroidal Aromatase Inhibitor, Letrozole, in Juvenile Rats
CONCLUSIONSThe observed effects in juvenile rats were considered predictable and primarily related to the mechanism of action of letrozole upon estrogen synthesis. (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 9, 2013 Category: Perinatology & Neonatology Authors: Louise Pouliot, Marilynn Schneider, Marc DeCristofaro, Rana Samadfam, Susan Y. Smith, David A. Beckman Tags: Original Article Source Type: research

Effects of Melamine and Cyanuric Acid on Embryo‐Fetal Development in Rats
After the outbreak of acute renal failure associated with melamine‐contaminated pet food, melamine and melamine‐related compounds have become of great interest from a toxicologic perspective. We investigated the potential effects of melamine in combination with cyanuric acid (M + CA, 1:1) on pregnant dams and embryo‐fetal development in rats. M + CA was orally administered to pregnant rats from gestational days 6 through 19 at doses of 0, 3, 10, and 30 mg/kg/day of both melamine and cyanuric acid. Maternal toxicity of rats administered 30 mg/kg/day M + CA was manifested as increased incidences of clinical signs and d...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 9, 2013 Category: Perinatology & Neonatology Authors: Sung‐Hwan Kim, In‐Chul Lee, Hyung‐Seon Baek, Kyeong‐Woo No, Dong‐Ho Shin, Changjong Moon, Sung‐Ho Kim, Seung‐Chun Park, Jong‐Choon Kim Tags: Original Article Source Type: research

Fertility and Developmental Toxicity Assessment in Rats and Rabbits with LY500307, a Selective Estrogen Receptor Beta (ERβ) Agonist
In conclusion, the no‐observed adverse effect levels following LY500307 administration were 1 mg/kg/day for male rat fertility, 0.3 mg/kg/day for female rat fertility and EFD, and 25 mg/kg/day for rabbit EFD. Adverse reproductive and developmental effects only occurred at or above parentally toxic dosage levels and were considered predominantly due to off‐target ERα effects. (Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology)
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 9, 2013 Category: Perinatology & Neonatology Authors: Kim G. Hilbish, William J. Breslin, Jason T. Johnson, Eddie D. Sloter Tags: Original Article Source Type: research

The Effect on Rat Embryonic Heart Rate of Na+, K+, and Ca2+ Channel Blockers, and the Human Teratogen Phenytoin, Changes with Gestational Age
In this study, we compared the effects of four ion channel blockers on rat embryonic heart function during the organogenic period from gestational day (GD) 10 to 15, to determine the changes in dependence on ion channels during rat cardiac development. Rat embryos in culture were exposed to either the human ether‐á‐go‐go‐related gene potassium channel blocker, dofetilide (400 nM); the sodium channel blocker, lidocaine (250 μM); the L‐type calcium channel blocker, nifedipine (1.8 μM); or the multichannel blocker, phenytoin (200 μM). Lidocaine slowed the heart rate (HR) with the effect becoming more severe wit...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 9, 2013 Category: Perinatology & Neonatology Authors: Mats F. Nilsson, Helen Ritchie, William S. Webster Tags: Original Article Source Type: research

Key Learnings from the Endocrine Disruptor Screening Program (EDSP) Tier 1 Rodent Uterotrophic and Hershberger Assays
This article describes two laboratories' experiences conducting Tier 1 uterotrophic and Hershberger assays. The uterotrophic assay detects estrogen receptor agonists through increases in uterine weight. The advantages of the uterotrophic rat models (immature vs. adult ovariectomized) and exposure routes are discussed. Across 29 studies, relative differences in uterine weights in the vehicle control group and 17α‐ethynylestradiol–positive control group were reasonably reproducible. The Hershberger assay detects androgen receptor (AR) agonists, antagonists, and 5α‐reductase inhibitors through changes in accessory sex...
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - December 1, 2013 Category: Perinatology & Neonatology Authors: M. Sue Marty, John C. O'Connor Tags: Original Article Source Type: research