OECD 414 supplementary prenatal developmental toxicity study of sodium molybdate dihydrate in the rat and benchmark dose evaluation.

In a continuing investigation of the potential for reproductive and developmental toxicity of molybdenum (Mo), consequent to the previous published OECD studies [1,2] and as directed by the European Chemicals Agency [3], a supplemental rat GLP-compliant Prenatal Developmental Toxicity (PNDT) study was conducted to investigate higher dose levels of sodium molybdate dihydrate (SMD) in an identical study design (OECD 414)[4] to Murray et al. 2014a [1], at dietary concentrations calculated to provide target Mo levels of 80 and 120 mg/kg bw/day (the maximum-tolerated dose). There was no effect on post-implantation loss, litter size, sex ratio or the incidence of external, visceral or skeletal fetal malformations or variations. Fetal weight was reduced proportionate to maternal dose. Minimal differences observed in the ossification status of some extremities of fetuses from females receiving 120 mg Mo/kg bw/day were confirmed as transient by skeletal examination of PND 21 pups from a further group of females receiving the same dose regime. There was no evidence of copper depletion in serum, placenta or liver. A benchmark dose evaluation using continuous and dichotomous approaches by combining the fetal body weight data from this study and the previous study determined that the BMD05 ranged from 47 to 57 mg Mo/kg bw/day, depending on the modelling approach and the BMDL05 estimates ranged from 37 to 47 mg Mo/kg bw/day. These levels are considered a more statistically robust point of departure for risk assessment for reproductive effects than the established NOAEL of 40 mg Mo/kg bw/day.

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in mice.

CD-1 mice were exposed to baseline gasoline vapor condensate (BGVC) alone or to vapors of gasoline blended with methyl tertiary butyl ether (G/MTBE). Inhalation exposures were 6h/d on GD 5-17 at levels of 0, 2000, 10,000, and 20,000mg/m(3). Dams were evaluated for evidence of maternal toxicity, and fetuses were weighed, sexed, and evaluated for external, visceral, and skeletal anomalies. Exposure to 20,000mg/m(3) of BGVC produced slight reductions in maternal body weight/gain and decreased fetal body weight. G/MTBE exposure did not produce statistically significant maternal or developmental effects; however, two uncommon ventral wall closure defects occurred: gastroschisis (1 fetus at 10,000mg/m(3)) and ectopia cordis (1 fetus at 2000mg/m(3); 2 fetuses/1 litter at 10,000mg/m(3)). A second study (G/MTBE-2) evaluated similar exposure levels on GD 5-16 and an additional group exposed to 30,000mg/m(3) from GD 5-10. An increased incidence of cleft palate was observed at 30,000mg/m(3) G/MTBE. No ectopia cordis occurred in the replicate study, but a single observation of gastroschisis was observed at 30,000mg/m(3). The no observed adverse effect levels for maternal/developmental toxicity in the BGVC study were 10,000/2000mg/m(3), 20,000/20,000 for the G/MTBE study, and 10,000/20,000 for the G/MTBE-2 study.

An assessment of the views held by recent graduates on their undergraduate course.

The aim of this study was to ascertain the views of recent graduates on their undergraduate training. 53 Vocational Training scheme organisers were contacted and 37 (70%) responded 391 new dentists on the schemes were sent postal questionnaires to record information on their views of the undergraduate dental curriculum, 247 questionnaires were returned giving a response rate of 63%. 62% of the subjects reported that they had received sufficient practical experience in the provision of crowns, 32% for veneers and 19% for bridgework. 46% of respondents felt able to treat a simple orthodontic case with removable appliances. 63% considered they had insufficient experience in surgical extractions, 40% expressed the opinion that overall, they would like more practical clinical experience included in the undergraduate course particularly in crown/bridgework and surgical extractions. In conclusion, there are areas in which recent graduates consider their undergraduate course to have been lacking.

A human health risk assessment of boron (boric acid and borax) in drinking water.

A human health risk assessment was conducted to derive an appropriate safe exposure level in drinking water of inorganic boron-containing compounds (boric acid and borax). Several regulatory agencies have set or plan to set drinking water guidelines or standards for boron (B). Recent publication of reproductive and developmental toxicity studies by the National Toxicology Program prompted this risk assessment, along with the understanding that boron may be nutritionally essential. A rat developmental toxicity study with a NOAEL of 9.6 mg B/kg/day was selected as the pivotal study on which to base this risk assessment, since it represents the most sensitive endpoint of toxicity. A detailed evaluation of these and other studies allowed modifications of the default values for uncertainty factors to account for the pharmacokinetic similarities among species, the lack of metabolism of inorganic boron-containing compounds, the similarity of the toxicity profile across species, the quality of the toxicological database, and other factors according to the approach described by Renwick previously. Benchmark dose calculations were performed, and the results were in close agreement with the NOAEL selected for this risk assessment. The Reference Dose was calculated to be 0.3 mg B/kg/day, resulting in an acceptable daily intake of 18 mg B/day. Considering that the U.S. average dietary intake of boron is 1.5 mg B/day, 16.5 mg B/day could be available for drinking water or other exposures, if any. A preliminary review of boron data in the National Inorganic Radionuclide Survey by the EPA indicates the median boron level in U.S. drinking water supplies to be 0.031 mg B/liter, and most exposures are less than 2.44 mg B/liter (99th percentile). It is concluded that boron in U.S. drinking water would not be expected to pose any health risk to the public.

A critical evaluation of the use of mutagenesis, carcinogenesis, and tumor promotion data in a cancer risk assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Regulatory agencies in the Western Hemisphere are currently assessing the potential human health risks of environmental contamination by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Some U.S. agencies such as the Environmental Protection Agency (EPA) and Centers for Disease Control (CDC) have assumed that TCDD behaves as a tumor initiator in animals and have used linear low-dose mathematical extrapolation models for estimating any human risk. In contrast, the Ontario Ministry of the Environment, the State Institute of National Health of The Netherlands, and the Federal Environmental Agency of the Federal Republic of Germany have concluded that TCDD does not have initiator activity; these agencies have advocated a risk extrapolation approach which applies a safety factor to a no-observable-effect level. Estimations of the potential risk obtained by these two approaches can differ by three to four orders of magnitude and have a major impact on the allocation of resources within the affected countries. This paper critically reviews the TCDD bacterial, animal, and human data on mutagenesis, carcinogenesis, and tumor promotion and concludes that the scientific evidence does not support risk estimations which are based on TCDD as a tumor initiator. Rather, the animal data overwhelmingly support TCDD as a tumor promoter. Risk estimations which incorporate tumor promotion activity more accurately reflect the scientific understanding of TCDD's mechanism of action and provide better estimates of its risk.