Relationship between bent long bones, bent scapulae, and wavy ribs: malformations or variations?

Background: Shortened and bent long bones and bent scapulae are sometimes reported in fetuses with wavy ribs (Carney and Kimmel, ). Wavy ribs are typically seen in the presence of maternal and developmental toxicity, are transient and reversible postnatally, and are considered to be variations rather than malformations.

Methods: We further assessed the literature cited in Kimmel and Carney () as well as papers published since then to determine under what conditions bent long bones in the absence of gross limb defects and bent scapulae were reported and whether information was available on the transient or permanent nature of these effects.

Evaluation of developmental toxicity studies of glyphosate with attention to cardiovascular development.

The herbicide glyphosate has undergone multiple safety tests for developmental toxicity in rats and rabbits. The European Commission's 2002 review of available glyphosate data discusses specific heart defects observed in several individual rabbit developmental toxicity studies, but describes the evidence for a potential causal relationship as equivocal. The present assessment was undertaken to analyze the current body of information generated from seven unpublished rabbit studies in order to determine if glyphosate poses a risk for cardiovascular malformations.

Potential effects of chlorpyrifos on fetal growth outcomes: implications for risk assessment.

Chlorpyrifos (CPF) is one of the most widely used organophosphate insecticides in the United States. By December 2000, nearly all residential uses were voluntarily canceled, so that today, CPF is only used to control insect pests on a variety of crops. Periodic review of the potential effects of CPF on all developmental outcomes is necessary in the United States because the Food Quality Protection Act mandates special consideration of risk assessments for infants and children.

Children's health risk assessment: incorporating a lifestage approach into the risk assessment process.

This overview paper provides the historical context for the incorporation of lifestage-specific concerns in human health risk assessment, briefly explains the process employed in a lifestage framework for risk assessment, and discusses the scientific rationale for how utilizing lifestage data will strengthen the overall risk assessment process. This risk assessment approach will add value by: (1) providing a more complete evaluation of the potential for vulnerability at different lifestages, including a focus on the underlying biological events and incorporation of mode of action information related to different critical developmental periods; (2) evaluating the potential for toxicity during all lifestages after early lifestage exposure; (3) reviewing the importance of integrating exposure information and adverse health effects across lifestages; and (4) serving as a basis to extend some aspects of the children's health risk assessment framework to all lifestages.

Public health implications of altered puberty timing.

Changes in puberty timing have implications for the treatment of individual children, for the risk of later adult disease, and for chemical testing and risk assessment for the population. Children with early puberty are at a risk for accelerated skeletal maturation and short adult height, early sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life.

Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs.

Delayed (or incomplete) ossification of developing fetal bones and wavy ribs are some of the most common skeletal variations encountered in regulatory guideline developmental toxicity studies. Although they tend to be regarded as minor effects, they can be quite sensitive and consequently may influence the study lowest-observed-adverse-effect levels (LOAELs), and thus, impact classification, labeling, and risk assessment. In this study, we review the underlying mechanisms of these skeletal variations, evaluate different scenarios in which they have been observed, offer guidance for their interpretation, and comment on their use for risk assessment.

Lessons learned for the National Children's Study from the National Institute of Environmental Health Sciences/U.S. Environmental Protection Agency Centers for Children's Environmental Health and Disease Prevention Research.

This mini-monograph was developed to highlight the experiences of the National Institute of Environmental Health Sciences (NIEHS)/U.S. Environmental Protection Agency (EPA) Centers for Children's Environmental Health and Disease Prevention Research, focusing particularly on several areas of interest for the National Children's Study.

Effects of hyperthermia and boric acid on skeletal development in rat embryos.

Background: The individual effects of boric acid (BA) and hyperthermia on the development of the axial skeleton have been reported previously. Both cause an increased incidence of axial skeletal defects including a decrease in the total number of ribs and vertebrae. Because of the similarity in the effects of the two agents, we examined their interaction when given in combination to pregnant rats on gestational day (GD) 10.

Adverse pregnancy outcomes associated with maternal enalapril antihypertensive treatment.

Background: Adverse pregnancy outcomes following the use of angiotensin-converting enzyme (ACE) inhibitors, including enalapril, have been reported in descriptive studies. However, no analytical studies on the relationship between the adverse outcomes and enalapril gestational exposures are available.

Objectives: To explore the association between enalapril exposure and adverse outcomes in pregnancy, taking into account other possible risk factors.

Children's health and the environment: public health issues and challenges for risk assessment.

Infants and children are not little adults. They are uniquely vulnerable to environmental toxicants. To protect infants and children against toxicants, the National Research Council in 1993 called for development of an approach to risk assessment that considers children's unique patterns of exposure and their special vulnerabilities to pesticides.

Atenolol developmental toxicity: animal-to-human comparisons.

Background: Atenolol, 4-2'-hydroxy-3'-isopropyl-aminopropoxy) phenylacetamide, is a beta-adrenoreceptor blocker used for treatment of hypertension in pregnancy. Beta-blockers are reported to cause fetal harm (such as decreased birth weight) when administered to a pregnant woman. We evaluate published human and animal evidence of atenolol developmental toxicity and compare the manifestations in humans and in routinely-used animal models.

The National Children's Study of environmental effects on child health and development.

Increasing recognition that children may be more susceptible than adults to environmental exposures and that they experience potentially life-long consequences of such exposures has led to widespread support for a large new cohort study in the United States. In this article, we propose a framework for a new cohort study of children, with follow-up beginning before birth and continuing to age 21 years. We also describe the administrative structure that has been built to develop the proposal further.

Response-surface modeling of the effect of 5alpha-dihydrotestosterone and androgen receptor levels on the response to the androgen antagonist vinclozolin.

Androgens secreted by the testes bind the androgen receptor in developing target tissues to induce the expression of genes required for male sexual differentiation and development. Androgen concentration and androgen receptor levels vary in male reproductive target tissues during development. Exposure to environmental androgen antagonists during critical windows of fetal and postnatal development can inhibit male sexual development by blocking transcription of androgen-dependent genes.

HSP90alpha, HSP90beta, and p53 expression following in vitro hyperthermia exposure in gestation day 10 rat embryos.

The studies presented here are aimed at understanding the expression of p53, HSP90alpha, and HSP90beta in gestation day (GD) 10 CD rat embryos. GD 10 rat embryos were exposed in vitro to 37 degrees C or 42 degrees C for 15 min, then cultured at 37 degrees C for 0.5, 1, 3, or 5 h.