Retarded ossification

In a double-stained skeleton the ossified bone will be stained red to purple and the cartilage blue (Figs. 1, 2, and 3). The staining of the cartilage allows the examiner to assess whether the underlying structure of a non-ossified bone is present and how it is shaped. The ratio of blue to red structures enables the investigator to discern accelerated or retarded ossification at a glance. 

In conclusion, similar to benzene, toluene does not appear to be teratogenic. It is fetotoxic, causing a reduction in fetal weight in mice and rats and retarded ossification and some increase in skeletal anomalies in rats at doses that are below those toxic to the dam as well as at toxic doses. Embryolethality has also been seen with inhalation of very high concentrations lethal to some of the dams or following oral administration of non-toxic doses. ... 

Air concentrations of 28.5 mg/m3 for 4 h daily on days 9-12 of gestation caused fetotoxic effects and chromosomal damage to liver cells by day 18 effects included reduced survival, impaired growth, retarded limb ossification, and bone abnormalities. At 2.9 mg/m3, a 9.9% decrease in fetal weight was recorded at 0.26 mg/m3, a 3.1% decrease was measured Oral dosages of 400-600 mg/kg BW on days 7-16 of gestation produces fetal malformations (cleft palate), delayed skeletal ossification, and fetal weight reduction 200-600 mg/kg BW daily for 10 days (DMA) produced fetal and maternal toxicity... 

Thyroid hormone also plays a major role in the maturation of bone. A deficiency of thyroid hormone in early life leads to both delay in and abnormal development of epiphyseal centers of ossification (epiphyseal dysgenesis). Hypothyroidism-induced impairment of linear growth can lead to dwarfism in which the Umbs are disproportionately short in relation to the trunk with the apparent bone age retarded in relation to chronological age. 

Rat (Sprague-Dawley) 10 d Gd 6-15 1 x/d (GO) 0.1 1 (subcutaneous edema) 10 (growth retardation, dilated renal pelvis, delayed ossification) Schwetz et al. 1973 HCDD5... 

Classification should not automatically be discounted for chemicals that produce developmental toxicity only in association with maternal toxicity, even if a specific maternally-mediated mechanism has been demonstrated. In such a case, classification in Category 2 may be considered more appropriate than Category 1. However, when a chemical is so toxic that maternal death or severe inanition results, or the dams are prostrate and incapable of nursing the pups, it may be reasonable to assume that developmental toxicity is produced solely as a secondary consequence of maternal toxicity and discount the developmental effects. Classification may not necessarily be the outcome in the case of minor developmental changes e.g. small reduction in foetal/pup body weight, retardation of ossification when seen in association with maternal toxicity. 

Enalapril, captopril, and lisinopril (and presumably other ACE inhibitors) cross the placenta in pharmacologically significant amounts (17). There is clear evidence of fetotoxicity when ACE inhibitors are used beyond the first trimester of pregnancy. Since continuation of treatment beyond the first trimester carries an excess risk of low fetal birth weight and other more severe complications, it is important to withdraw the ACE inhibitor at this time. Intrauterine growth retardation, oligohydramnios, and neonatal renal impairment, often with a serious outcome, are characteristic (98) failure of ossification of the skuU or hypocalvaria also appear to be part of the pattern (17). There is also evidence that persistence of a patent ductus arteriosus is also more likely to occur. 

Thyroid hormone stimulates production of IGF-I directly (liver) and indirectly (via increased growth hormone, GH). In adults with hypothyroidism, basal serum GH levels are normal, but the GH responses to provocative stimuli, nocturnal GH secretion, and serum IGF-I are all subnormal. In cretinism (infantile hypothyroidism), linear growth is severely retarded and the resultant dwarfism is characterized by a retention of the high upper to lower body ratio of infancy. The growth retardation in persons with cretinism is primarily due to delayed appearance of ossification centers in long bone, and secondarily to a deficiency in growth factors. 

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