Article

Altered axial skeletal development

Center for Life Sciences and Toxicology, Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194, USA.
Birth Defects Research Part B Developmental and Reproductive Toxicology (Impact Factor: 1.17). 12/2007; 80(6):451-72. DOI: 10.1002/bdrb.20134
Source: PubMed

ABSTRACT The axial skeleton is routinely examined in standard developmental toxicity bioassays and has proven to be sensitive to a wide variety of chemical agents. Dysmorphogenesis in the skull, vertebral column and ribs has been described in both human populations and in laboratory animals used to assess potential adverse developmental effects. This article emphasizes vertebrae and rib anomalies both spontaneous and agent induced. Topics discussed include the morphology of the more common effects; incidences in both human and experimental animal populations; the types of anomalies induced in the axial skeleton by methanol, boric acid, valproic acid and others; the postnatal persistence of common skeletal anomalies; and the genetic control of the development of the axial skeleton. Tables of the spontaneous incidence of axial anomalies in both humans and animals are provided.

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    • "Further, stunted growth of the skeleton can predispose infants, children , and adolescents to increased risk of fracture much later in life (Cooper et al., 1997; Heaney et al., 2000). However, many observed effects on the skeleton such as fused vertebrae, supernumerary ribs, and other axial anomalies or malformations are teratological and occur due to prenatal genetic and environmental factors (Tyl et al., 2007). Prenatal observance of delayed ossification or wavy ribs do not sufficiently predict postnatal permanent defects, as effects on ossification or formation of wavy ribs in the fetus can be remediated in the early postnatal period (Carney and Kimmel, 2007). "
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    ABSTRACT: Differences in the physiology and biological susceptibilities of adults and infants have led to growing interest in safety evaluation methods for exposures from infant formula packaging. In addition to potential physiological differences, infants aged 0 - 6 months may consume a sole source of food, infant formula or breast milk, and consume higher amounts of food relative to body weight compared to adults. While the duration of the exposure is short compared to the expected lifespan of the individual, it occurs during a period of important developmental processes. The purpose of this document is to (1) review key biological and exposure elements that may impact the evaluation of safety for food contact products intended for use by infants, (2) summarize the current reproductive and developmental toxicity testing protocols available, and (3) identify potential data gaps concerning this period of development.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2014; 70. DOI:10.1016/j.fct.2014.05.003 · 2.61 Impact Factor
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    • "Further, stunted growth of the skeleton can predispose infants, children , and adolescents to increased risk of fracture much later in life (Cooper et al., 1997; Heaney et al., 2000). However, many observed effects on the skeleton such as fused vertebrae, supernumerary ribs, and other axial anomalies or malformations are teratological and occur due to prenatal genetic and environmental factors (Tyl et al., 2007). Prenatal observance of delayed ossification or wavy ribs do not sufficiently predict postnatal permanent defects, as effects on ossification or formation of wavy ribs in the fetus can be remediated in the early postnatal period (Carney and Kimmel, 2007). "
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    ABSTRACT: Differences in the physiology and biological susceptibilities of adults and infants have led to growing interest in safety evaluation methods for exposures from infant formula packaging. In addition to potential physiological differences, infants aged 0–6 months may consume a sole source of food, infant formula or breast milk, and consume higher amounts of food relative to body weight compared to adults. While the duration of the exposure is short compared to the expected lifespan of the individual, it occurs during a period of important developmental processes. The purpose of this document is to (1) review key biological and exposure elements that may impact the evaluation of safety for food contact products intended for use by infants, (2) summarize the current reproductive and developmental toxicity testing protocols available, and (3) identify potential data gaps concerning this period of development.
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    • "During development, the factors affecting the pattern formation of the axial skeleton remain poorly understood. Genetic variations, either resulting from spontaneous mutations or because of xenobiotic exposure may disrupt this patterning and lead to a wide variety of skeletal alterations [13] [14]. "
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    ABSTRACT: There are few studies that have addressed the effects of prenatal exposure of topiramate on ossification of the bones derived from the paraxial mesoderm. This study aimed to evaluate skeletal ossification of ribs and vertebrae in 20-day-old rat fetuses after maternal exposure to two therapeutic doses of topiramate. Three groups of Sprague-Dawley pregnant rats were used: control, topiramate 50 mg/kg/day and topiramate 100 mg/kg/day treated groups. Topiramate was administered by gavage from day 6-19 of gestation. Fetuses were collected on day 20 by caesarean section. Fetal bones were stained with alizarin red and ossification was assessed. Results showed significant delayed ossification of ribs and vertebrae in topiramate-exposed fetuses at both doses and the effects were not dose dependent. In all examined groups, there was a direct correlation between the fetal weight and the number of complete ossified vertebral centers. Also, there were significant increases in skeletal abnormalities, particularly in ribs in both treated groups when compared to the control group. In conclusion, therapeutic doses of topiramate should be taken cautiously during pregnancy as they lead to fetal growth restriction and increases abnormalities of axial skeleton in rat fetuses.
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