Incidence Of Resorption Research Articles

Adenoviral Delivery of VEGF 121 Early in Pregnancy Prevents Spontaneous Development of Preeclampsia in BPH/5 Mice

An imbalance in circulating proangiogenic and antiangiogenic factors is postulated to play a causal role in preeclampsia (PE). We have described an inbred mouse strain, BPH/5, which spontaneously develops a PE-like syndrome including late-gestational hypertension, proteinuria, and poor feto-placental outcomes. Here we tested the hypothesis that an angiogenic imbalance during pregnancy in BPH/5 mice leads to the development of PE-like phenotypes in this model. Similar to clinical findings, plasma from pregnant BPH/5 showed reduced levels of free vascular endothelial growth factor (VEGF) and placental growth factor (PGF) compared to C57BL/6 controls. This was paralleled by a marked decrease in VEGF protein and Pgf mRNA in BPH/5 placentae. Surprisingly, antagonism by the soluble form of the FLT1 receptor (sFLT1) did not appear to be the cause of this reduction, as sFLT1 levels were unchanged or even reduced in BPH/5 compared to controls. Adenoviral-mediated delivery of VEGF(121) (Ad-VEGF) via tail vein at embryonic day 7.5 normalized both the plasma-free VEGF levels in BPH/5 and restored the in vitro angiogenic capacity of serum from these mice. Ad-VEGF also reduced the incidence of fetal resorptions and prevented the late-gestational spike in blood pressure and proteinuria observed in BPH/5. These data underscore the importance of dysregulation of angiogenic factors in the pathogenesis of PE and suggest the potential utility of early proangiogenic therapies in treating this disease.

Mast cells and MMP‐9 in the lamina propria during eruption of rat molars: quantitative and immunohistochemical evaluation

During the active tooth eruption process, structural changes in the lamina propria are necessary to provide extracellular matrix remodelling and for the establishment of the eruptive pathway. A large number of resident cells, recruited cells and proteases have been demonstrated in the eruptive process, but the participation of MMP-9 and mast cells has not yet been demonstrated. In this study, we set out to evaluate the intensity of MMP-9 immunoexpression, the frequency of mast cells and the correlation between the incidence of mast cells and bone resorption in different phases of tooth eruption. Fragments of maxilla containing first molars, obtained from 9-, 11-, 13- and 16-day-old rats, were fixed in 4% formaldehyde, decalcified and embedded in paraffin. Sagittal sections were stained with Masson's trichrome or submitted to the tartrate-resistant acid phosphatase method for quantification of osteoclasts. Sections stained by 1% toluidine blue were used for quantification of metachromatic mast cells mm(-2) of lamina propria. The expression of MMP-9 in the lamina propria was evaluated by immunohistochemistry. In the 9-day-old rats, the lamina propria contained few mast cells and occasional osteoclasts were found in the bone surface overlying the occlusal portion of the tooth germs. Otherwise, a significant increase in the number of mast cells was observed in the intra-osseous phase of tooth eruption (11-day-old rats), period in which numerous TRAP-positive osteoclasts were found in the bone surface. MMP-9 immunolabelling was detected in fibroblasts, mast cells and macrophage-like cells of the lamina propria in all ages studied. However, an enhanced immunolabelling was evident in the advanced phase of tooth eruption (16-day-old rats). During the intra-osseous phase, the parallel between the high frequency of both mast cells and osteoclasts suggests that mast cells could exert a paracrine function on the osteoclasts and then stimulate bone resorption. The immunoexpression of MMP-9 in different cells of lamina propria, including mast cells, indicates that this enzyme participates in the degradation of ECM, mainly during late phase of mucosal penetration. Thus mast cells and MMP-9 are involved in the complex process of degradation of the eruptive pathway extracellular matrix.

Analysis of Cranioplasty Using Frozen Autologous Bone Following Post-Traumatic Decompressive Craniectomy

Objective: We conducted this study to evaluate outcome of delayed cranioplasty using frozen autologous bone flap following decompressive craniectomy in patients with traumatic brain injury. Methods: In 27 patients, 30 sites have undergone cranioplasty using frozen autologous bone flaps in the past 3 years. After decompressive craniectomy, bone flaps were stored at -40°C for 3 to 316 days (mean, 55.6 days). Bone flaps were thawed at room temperature before cranioplasty and repositioned. Serial follow-up of skull x-ray and/or computed tomography was performed to monitor bony resorption and other complications. Follow-up periods ranged from 9 to 46 months (mean, 20 months). Results: There was no surgically related complications. In 9 sites (30%), potoperative bone resorption was noted. Among them 3 sites underwent ventriculoperitoneal shunt (VPS) with multiple skull fractures and 2 sites underwent VPS without multiple skull fractures and 2 sites was with multiple bone fracture alone. In 7 sites with multiple skull fractures, resorption developed in 4 sites (57.1%) and 5 sites (83.3%) had resorption out of 6 sites with VPS. However, the aesthetic results were not dissatisfactory and a second cranioplasty was not indicated. Conclusion: Cranioplasty using frozen autologous bone following post-traumatic decompressive craniectomy is associated with a high incidence of bone resorption, especially in patients with multiple skull fracture or VPS, even though the aesthetic results were not dissatisfactory. The most important factor for successful bone union was manipulation of bone flap in cranioplasty to facilitate bone resorption followed by accretion. Further improvements are required to perform cranioplasty in patients with VPS. (J Kor Neurotraumatol Soc 2010;6:13-17)

Long-Term Results of Total Hip Arthroplasty with an Extensively Porous Coated Stem in Patients Younger than 45 Years Old

PurposeThis study analyzed the long-term results of cementless total hip arthroplasty using an extensively porous coated stem in patients younger than 45 years old.Materials and MethodsThe clinical and radiographic results of 45 hips from 38 patients who underwent cementless total hip replacement arthroplasty with an AML prosthesis were reviewed retrospectively. The average follow-up was 12 years (range, 10-15 years).ResultsThe average Harris hip score at the time of final follow-up was 87.3 (range 77-94) points. Forty two hips (93.3%) showed excellent and good clinical results. Osteolysis occurred around the stem in 20 hips (44.4%) and around the cup in 26 hips (57.8%). Stress-mediated femoral resorption was observed in 33 hips (73.3%) at 10 years. There was no incidence of resorption progressing after 5 years postoperatively. There was no stem loosening. Five hips were revised for osteolysis, cup loosening and polyethylene wear.ConclusionThe long term results of total hip arthroplasty using an extensively porous coated stem were acceptable, and there was no case involving the progression of proximal bone resorption.

Effect of recombinant basic fibroblast growth factor on reimplanted teeth in beagle dogs

This study assessed the effect of recombinant fibroblast growth factor (FGF-2) on reimplanted teeth. Premolars were reimplanted in dogs. Roots on the left side of the mandible were treated with FGF-2, whereas roots on right side served as controls. At 2, 4, or 8 weeks after treatment, animals were humanely killed and specimens collected and processed for histopathologic examination. After 2 weeks, proliferating cell nuclear antigen-positive cell ratios in the experimental group were significantly greater than those in the control group (P < .01). After 4 and 8 weeks, the experimental group showed formation of new cementum. Moreover, incidence of replacement resorption in the experimental group was significantly lower than that in the control group (P < .01). The results indicate that FGF-2 promotes formation of new periodontal ligament and prevents ankylosis and root resorption following reimplantation of teeth.

Skeletal Stability and Complications of Bilateral Sagittal Split Osteotomies and Mandibular Distraction Osteogenesis: An Evidence-Based Review

To provide an evidence-based review comparing the skeletal stability and complications of bilateral sagittal split osteotomies (BSSOs) and mandibular distraction osteogenesis (MDO) in the treatment of mandibular hypoplasia. A Medline search from January 1957 to December 2007 was performed wherein articles were retrieved on the basis of a set of inclusion and exclusion criteria. Data on mean skeletal stability and complications for the 2 techniques were retrieved from these articles. Based on the articles about stability, patients undergoing BSSO or MDO with an advancement or lengthening between 6 and 10 mm showed a similar mean skeletal relapse of 15.0% and 17.1%, respectively, within postoperative months 6 to 12. Greater skeletal relapse was reported for BSSO patients with high mandibular plane angles compared with normal mandibular plane angle patients (29.6% vs 11.3%). Based on the articles about complications, patients who underwent MDO showed a lower incidence of persistent inferior alveolar nerve disturbance (2.9%) and condylar resorption (1.4%) compared with BSSO patients, in whom the incidence of these conditions was 27.8% and 6.1%, respectively. Both BSSO and MDO showed similar relapse rates for mandibular advancements between 6 and 10 mm. Both techniques may also share similar risk factors for skeletal relapse. BSSO has a higher incidence of persistent neurosensory disturbances and condylar resorption than MDO. Randomized controlled trials of these 2 techniques are still lacking.

Dentinal anomalies in teeth of harbour porpoises (Phocoena phocoena) from Scottish waters: are they linked to sexual maturation and environmental events?

We examined the tooth ultra-structure of harbour porpoises (Phocoena phocoena) from Scottish waters to determine whether the incidence of mineralization anomalies could be related to certain life history events (e.g. the achievement of sexual maturation) as well as other factors that affect the general health of the individual (e.g. persistent organic pollutant (POP) concentrations in blubber). Five distinct types of mineralization anomalies were recorded: accessory lines, marker lines, dentinal resorption, cemental disturbance and pulp stones and the occurrence of these anomalies was scored by sex, age and maturity state. Overall, the incidence of mineralization anomalies was high and tended to increase with age. Marker lines and accessory lines were the most commonly recorded anomalies while pulp stones were least frequent. Duplicate teeth (i.e. from the same individual) always showed the same pattern of anomaly occurrence.Fitted binary generalized linear and additive models indicated that the presence of dentinal resorption, cemental disturbance and marker lines in harbour porpoise teeth increased with age, body length and maturity. Males displayed marker lines more frequently than females. Age was the best predictor of the incidence of dentinal resorption and cemental disturbance while age and sex were the best predictors of the incidence of marker lines. The time course of appearance of dentinal resorption and cemental disturbance suggests that their occurrence could be related to physiological stress linked to sexual maturation. Marker lines were found within growth layer groups which coincided with the beginning of weaning and sexual maturation, suggesting an association with these two major life history events. Accessory lines were found in most teeth and may be a normal characteristic of porpoise teeth or reflect regular events. Pulp stones appeared only in mature animals. We found no evidence that the presence of anomalies in teeth was significantly related to POP concentrations in the blubber.

The role of C5a in reproductive impairment in the mouse and human

Adequate dietary folate is essential for a healthy pregnancy. Folate deficiency during pregnancy has been shown to contribute to foetal demise, growth retardation, craniofacial, cardiovascular, and neural tube defects, and numerous other congenital abnormalities. The present study aimed to determine whether the complement factor C5a contributes to folate-deficiency induced reproductive impairment, given that recent investigations have demonstrated that C5a can contribute to pathology in both antibody-dependent and -independent models of pregnancy loss. Administration of a folate-deficient diet (FDD) to wildtype mice resulted in poor fertility, reduced birth weights, and a high incidence of foetal loss. In contrast, C5a receptor knockout (C5aR KO) mice were resistant to foetal loss induced by a FDD, with a comparable incidence of resorption to mice administered a folate replete diet. C5aR-deficient mice on a FDD had significantly reduced birth weights and a very high prevalence of neural tube defects (40%)—a much higher frequency than FDD-fed wildtype mice. This observation suggests that in the presence of C5a, otherwise non-viable embryos from folate-deficient dams are rescued, resulting in an increased frequency of major birth defects. We also studied the expression of complement in human placenta. Placentas from growth restricted babies exhibited significant placental deposition of the upstream complement factor C3 compared to healthy controls. Intriguingly, when foetal growth restriction was associated with preeclampsia, an upregulation of placental C5aRs was additionally observed. These results suggest a complex role for the complement system and for C5a in foetal health and survival.

Ca(OH)2 pulpotomy in primary teeth. Part I: internal resorption as a complication following pulpotomy

The aim of this study was to analyze the outcomes of Ca(OH)(2) pulpotomies, to investigate the incidence of internal resorption following pulpotomy, and to investigate the relationship between internal resorption and physiological root resorption. Pulpotomies were performed in 84 primary molars. Teeth were grouped according to type of exposure (mechanical or carious) and according to whether or not physiological root resorption has started. All teeth were followed for 12 months. Teeth with larger-than-pinpoint carious exposure had the lowest success rate (65.5%). Internal resorption accounted for 15 out of 17 failures (88.2%). There was no significant difference in the rate of internal resorption between teeth with and without physiological root resorption (19.6% and 15.8%, respectively; P > .05). The greater the area of carious exposure, the lower the success rate in pulpotomies. Internal resorption was the main reason for failure; however, internal resorption was not affected by physiological root resorption.

Reproductive Toxicity Evaluation of Pestban Insecticide Exposure in Male and Female Rats.

Sexually mature male and female rats were orally intubated with the organophosphorus insecticide, Pestban at a daily dosage of 7.45 or 3.72 mg/kg bwt, equivalent to 1/20 and 1/40 LD50, respectively. Male rats were exposed for 70 days, while the female rats were exposed for 14 days, premating, during mating and throughout the whole length of gestation and lactation periods till weaning. The results showed depressed acetylcholinesterase (AChE) activity in the brain of parents, fetuses and their placentae in a dose-dependent manner. The fertility was significantly reduced with increasing the dose in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre-and postimplantation losses were significantly increased. The incidence of resorptions was more pronounced in treated female compared to male group and was dose dependant. The behavioral responses as well as fetal survival and viability indices were altered in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group and occurred in a dose-related manner. The recorded morphological, visceral, and skeletal anomalies were significantly increased with increasing the dose in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to Pestban would cause adverse effects on fertility and reproduction.

Hydroxyapatite-Bioactive Glass Ceramic Composite as Stand-alone Graft Substitute for Posterolateral Fusion of Lumbar Spine: A Prospective, Matched, and Controlled Study

Prospective, matched, and controlled study. To evaluate the efficacy of hydroxyapatite-bioactive glass ceramic composite (Chitra-HABg) as a stand-alone graft substitute in promoting posterolateral fusion in the lumbar spine as compared with autologous bone. The use of ceramics as stand-alone graft substitutes in posterolateral fusion remains controversial. The Chitra-HABg is a new composite that has undergone clinical trials in various orthopedic applications with excellent clinical and radiologic outcomes. Twenty-four patients underwent instrumented posterolateral fusion, with Chitra-HABg laid on the left intertransverse bed and autogenous graft on the right side. The primary outcome measure was radiologic consolidation of the graft, and secondary outcome measures were the work status and the Modified Oswestry Disability index. The McNamara and Student chi test were applied for statistical analysis. Although the study was prematurely terminated owing to the high incidence of resorption of Chitra-HABg, 22 of the 24 subjects were followed-up for a minimum of 1 year. At the end of 1-year, excellent radiologic outcome was seen on the right side (autogenous graft) in all the cases, whereas 95% (21/22) of the cases had poor consolidation on the left side (Chitra-HABg). The clinical outcome was rated as good in 16/22 (73%) patients, fair in 5, and poor in only 1 patient, but this had no statistically significant association with the consolidation of the fusion mass. This study clearly demonstrates that hydroxyapatite-bioactive glass ceramic composites (Chitra-HABg) has no role as stand-alone bone graft substitutes in posterolateral fusion of the lumbar spine, as the composite undergoes resorption without the formation of bridging callus. Level 1.

Evaluation of the developmental toxicity of diallyl phthalate administered orally to rats

The objective of this study was to evaluate the developmental toxic potential of diallyl phthalate (DAP) in rats. Pregnant Sprague-Dawley rats were given DAP at doses of 0 (olive oil), 100, 150, 200, and 250mg/kg/day, by gavage (5ml/kg), on Gestational Days (GD) 6 through 20. Gross examination at necropsy revealed liver lesions in dams given 150mg/kg/day or higher doses. In addition, maternal weight gain and food consumption were significantly reduced at 200 and 250mg/kg/day. There was no significant increase in the incidence of resorptions, or malformations, at any dose. Fetal body weight was significantly reduced at 200 and 250mg/kg/day. There was a significant increase in the incidence of fetuses with skeletal variations at 250mg/kg/day. Retarded ossification of certain bones (i.e. forelimb and hindlimb phalanges, metatarsals, and caudal vertebrae) was also observed. There was no sign of developmental toxicity at 100 and 150mg/kg/day.Thus, DAP caused fetal toxicity at doses which also produced maternal effects, but no embryolethality or teratogenicity.

The relationship between dung quality and oocyte resorption in laboratory and field populations of Lucilia cuprina

AbstractOocyte resorption in Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) is indicative of protein shortages during ovarian development. It is commonplace in field populations and is thought to reflect the species’ dependence on sheep dung as its primary source of protein. To test this proposition, resorption was monitored in flies fed with sheep dung collected when pastures varied from lush to drought affected. Laboratory assays showed that the proportion of females that became gravid, their rate of ovarian development, and the size and number of oocytes matured all decreased significantly as the protein content of the food source decreased. Conversely, the number of oocytes resorbed increased as dung protein decreased. However, estimates of dung quality (DQ), as derived from a pasture growth–DQ model, were not informative in explaining the seasonal or regional prevalence of resorption in flies collected over several years in three widely disparate sheep‐grazing areas. Recalibration of the DQ model to provide daily estimates of dung protein, which were then used to predict the incidence of oocyte resorption at different times of the year, also failed to show any systematic effects. There was, however, a clear tendency for this model to underestimate the extent of resorption in field populations. Because wild flies would have ready access to a wide variety of food sources, many of which would have been more nutritious than sheep dung, this finding is contrary to expectation and hence the nutritional role of sheep dung merits further study.

Age-dependent external root resorption during tooth movement in rats

Objective. To investigate the effect of age on root resorption and distribution along different parts of the root during prolonged light force application. Material and methods. Orthodontic appliances were placed in two groups of 30 rats (one group 6 weeks old, the other 9–12 months old), with contralateral sides as controls. Groups of animals were killed at 1, 2, 4, 8, and 12 weeks. At the study site, incidence was counted as either 1 (with resorption) or 0 (without); severity was measured as the summed length of all resorption lacunae as a percentage of study total root length. Results. Young and adult rats had the same incidence of root resorption in the early phase (<4 weeks), and both increased in the late phase (4–12 weeks) to the same level. Severity of resorption increased with prolonged tooth movement only in adult rats. However, there was no age-related difference in either the early or the late phase. In both groups, the middle part of the root had the highest incidence of resorption; the most severe resorption occurred exclusively at this part. Conclusion. Orthodontic intervention even with light forces increased both the incidence and severity of root resorption, the more so in the middle part of the root. Adult rats had increased incidence and severity with prolonged tooth movement.

Reproductive toxicity of lapachol in adult male Wistar rats submitted to short‐term treatment

Lapachol is a therapeutic naphthoquinone, but little is known about its general and reproductive toxicity. In female rats, a high incidence of resorptions and fetal mortality has been reported. This work analyses the effect of the short-term administration of lapachol on vital and reproductive organs, and sperm production in Wistar rats. Adult animals were treated with 1 mL of lapachol hydroalcohol solution (100 mg/kg of body weight) for 5 days and killed 3 (T1) and 14 days (T2) after the end of treatment. Body and organ weights and sperm production were evaluated. The administration of lapachol significantly reduced the weight of the seminal vesicle (T1 animals). No significant alteration of gamete production, body weight and the weight of the other organs analysed were detected. The results suggest a reproductive toxicity effect of lapachol, indicating the seminal vesicle as a possible target organ.

Developmental toxic effects of N‐ethyl‐2‐pyrrolidone administered orally to rats

The developmental toxicity of N-ethyl-2-pyrrolidone (NEP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given NEP at doses of 0 (distilled water), 50, 250, 500 and 750 mg kg(-1) day(-1), by gavage (5 ml kg(-1)), on gestational days (GD) 6-20. Maternal toxicity, as evidenced by reduction in body weight gain and food consumption, was observed in all NEP groups at the beginning of treatment (GD 6-9). The incidence of resorptions was significantly increased at 500 mg kg(-1) day(-1), and reached 83% at 750 mg kg(-1) day(-1). There was a dose-related decrease in fetal weight, which was significantly lower than control at 250 mg kg(-1) day(-1) and higher doses. The incidence of malformed fetuses per litter and the number of litters with malformed fetuses were significantly increased at 500 and 750 mg kg(-1) day(-1). Malformations mainly consisted of edema, anal atresia with absent tail, cardiovascular defects and fused cervical arches. Ossification of skull bones and sternebrae was significantly reduced at 500 and 750 mg kg(-1) day(-1). The incidence of supernumerary ribs was significantly elevated at 250 mg kg(-1) day(-1) and higher doses. In conclusion, NEP administered by gavage is embryotoxic and teratogenic at maternal toxic doses.

Reproductive safety studies with genistein in rats

Genistein is a phytoestrogen that occurs naturally in the diet and is found in a wide variety of plant-derived foods especially in soybeans and soy-based foods. There is wide spread interest in genistein and related phytoestrogens as chemopreventive agents for a variety of human diseases and cancers based on epidemiologic evidence of reduced cancer rates in populations with a high intake of soy. Soy, and hence its constituents, such as genistein, have been consumed at high levels in several Asian populations for many centuries without any apparent adverse effects and to the contrary, many health benefits have been associated with the ingestion of soy based foods. Concern has been raised, however, of potential adverse effects due to the estrogenic and other activities of the isoflavones and thus a comprehensive series of safety studies was performed with genistein. To assess the teratogenic and fetal toxic potential of genistein, several studies were conducted. Genistein was tested in an in vitro rat whole embryo culture assay (WEC), which is a preliminary screen, for fetotoxic and teratogenic potential, over a concentration range of from 1 to 100 μg/mL. Treatment related anomalies were observed at concentrations of ⩾10 μg and at 100 μg/mL, all embryos were malformed. Two in vivo embryo fetal developmental safety studies were conducted with genistein by oral administration (gavage and dietary admix) in which there was no evidence for a teratogenic effect. In an oral (gavage) embryonic and fetal development pilot study, genistein was administered to rats at dose levels of 0, 20, 150 and 1000 mg/kg/day from days 6–20 of gestation to females that were allowed to litter and rear their offspring up to day 7 of lactation. A slight maternal toxicity at 1000 mg/kg/day was observed as indicated by decreased body weight and food consumption and at this dose, adverse effects in the pups were observed including increased pup mortality, poor general condition, reduced pup body weights, and reduced pup milk uptake. At the high dose of 1000 mg/kg, no external malformations were noted, however some minor visceral and skeletal variations were observed. At the low dose of 20 mg/kg/day, an increased mortality, reduced milk uptake, a decreased % male sex ratio, and decreased body weights during lactation were observed. Due to lack of effects at the mid dose and the small number of animals, a relationship to treatment was considered unlikely. In an oral (dietary admix) Prenatal developmental safety study, genistein was administered to rats at dose levels of 0, 5, 50, 100 and 500 mg/kg/day from day 5–21 of gestation. At 500 mg/kg, maternal body weight and food consumption were markedly reduced. The incidence of resorptions was markedly increased with a corresponding decrease in the number of live fetuses per dam. Fetal body weights were also reduced. No treatment-related teratogenic effects were noted during external, visceral and skeletal examination of fetuses or in body weight normalized anogenital distance. On the basis of these studies, it is concluded that genistein has no teratogenic potential in vivo at very high doses of up to 1000 mg/kg/day by oral gavage in the embryo-fetal toxicity pilot study or up to 500 mg/kg/day by dietary admix in the Prenatal developmental study even though these doses were maternally toxic and fetal-toxic. In vitro, genistein had teratogenic potential at high concentrations in the WEC screening assay, however this was not predictive of the in vivo findings. On the basis of the definitive Prenatal development study, the NOAEL for maternal toxicity and adverse effects on embryonic development was considered to be 100 mg/kg/day when administered orally by dietary admix.

Developmental toxic effects of antifungal flusilazole administered by gavage to mice

The developmental toxicity of flusilazole was studied in CD-1 mice after oral administration. Pregnant mice were given flusilazole at doses of 0 (corn oil), 10, 20, and 40 mg/kg/day, by gavage, on gestational days (GD) 6-15. Maternal toxicity, as evidenced by reduction in body weight gain and signs of toxicity, was observed at the middle- and high-dose groups. No significant incidence of resorptions or death was observed in any of dose groups. There was a pronounced reduction in fetal weight, which was significantly lower than control from 20 and 40 mg/kg/day. There was no significant increase in the incidence of fetuses with external or visceral malformations in any of dose groups, but there was a significant increase in the incidence of skeletal malformations was observed at 20 and 40 mg/kg/day. The results of this study reported marked maternal toxicity, growth retardation, and skeletal abnormalities in the mid- and high-dose groups. It seems likely that marked maternal toxicity contributed to the observed alterations in fetal growth retardation and skeletal development. The no-observed-effect level in the present study for maternal and developmental toxicity was 10 mg/kg/day.

Developmental toxic effects of chronic exposure to high doses of iodine in the mouse

Chronic exposure to high doses of iodine induces thyroid dysfunction, but effects of chronic exposure to high amounts of iodine on pregnancy and fetal outcome are uncertain. In the present study, Balb/C mice were given different doses of iodine at the levels of 0 (sterile water), 1500, 3000, 6000, 12,000 and 24,000 μg/L in drinking water for 4 months, then were mated and the developmental toxicity and teratogenicity were evaluated. An obvious colloid goiter was observed, and serum total thyroxine (TT 4) levels increased and serum total triiodothyronine (TT 3) levels decreased significantly in dams when iodine dose reached 3000 μg/L. Maternal effect was evident by the reduction of average daily food consumption in higher doses of iodine groups. Embryotoxicity and teratogenicity were mainly indicated by the reduced body weight in female fetuses, the decreased number of live fetuses, and the increased incidence of resorptions, and especially skeletal variations. These results suggest that exposure to maternally toxic doses of iodine may have a potential developmental toxic effect.

Developmental toxic effects of diisobutyl phthalate, the methyl-branched analogue of di- n-butyl phthalate, administered by gavage to rats

The developmental toxicity of diisobutyl phthalate (DIBP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given DIBP at doses of 0 (olive oil), 250, 500, 750, and 1000 mg/kg/day, by gavage (5 ml/kg), on gestational days (GD) 6 through 20. Maternal toxicity, as evidenced by reduction in body weight gain, was observed at the beginning of treatment (GD 6–9), at 500 mg/kg and higher doses. The incidence of resorptions was significantly increased at 750 mg/kg, and reached 60% at 1000 mg/kg. There was a dose-related decrease in fetal weight, which was significantly lower than control from 500 mg/kg. A significant increase in the incidence of fetuses with visceral and skeletal malformations was seen at 750 and 1000 mg/kg. In particular, fused sternebrae occurred at a significantly higher frequency. Two skeletal variations were increased at 750 and 1000 mg/kg: retarded ossification of vertebrae, and predominantly, supernumerary ribs. The incidence of male fetuses with undescended testes was also significantly elevated at the two highest doses. In conclusion, DIBP administered by gavage is embryotoxic and teratogenic, and affects the developing male reproductive tract, at maternal toxic doses.