Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Apr 2004
Comparative StudyThe safety of ethyl oleate is supported by a 91-day feeding study in rats.
The purpose of this study was to determine the safety of ethyl oleate (EO) in a 91-day feeding study in Sprague-Dawley rats. EO was mixed into AIN-93G purified diet at levels of 0, 3.3, 6.7, and 10% by weight (the high-dose males and females consumed 5.5 and 6.1g/kg/day EO, respectively). All diets were calorie- and fat-matched using high oleic safflower oil (HOSO) as the control fat. ⋯ There was a dose-related increase in fecal fat concentration in both sexes from approximately 9% (control) to 18% in males, and from 4 (control) to 13% in females There were no visually obvious differences with regard to feces quality or quantity at any level of EO in the diet (i.e., color, diarrhea, weight, etc.). The increase in fat most likely represents small amounts of unabsorbed EO at the mid- and high-dose (estimates of EO absorption in this study are >80%). The No Observable Adverse Effect Level was determined to be 10% EO when administered daily in the diet for 91-days (approximately 6g EO/kg bw/day).
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Regul. Toxicol. Pharmacol. · Jun 2002
Dermal absorption in rhesus monkeys of polychlorinated biphenyls from soil contaminated with Aroclor 1260.
Human health risk assessments involving contaminated soil include dermal absorption as a potential pathway contributing to the total exposure burden. For PCB-contaminated soil, the U. S. ⋯ The base soil used in the current study with Aroclor 1260 had an organic content of 5-6% (< or =2 mm particle fraction), a value typical for U. S. soil. The organic content of the soil applied to the skin was 8.7% (<150 microm particle fraction), a value that contrasts sharply with the soil containing 0.9% organics used in the 1993 study with Aroclors 1242 and 1254 that produced a dermal absorption value of 14% for PCBs.
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Regul. Toxicol. Pharmacol. · Apr 2002
An analysis of the mainstream smoke chemistry of samples of the U.S. cigarette market acquired between 1995 and 2000.
Surveys of the smoke composition of commercially marketed cigarettes were conducted in 1995, 1998, and 2000. For each of these surveys, the U. S. cigarette market was stratified into broad market sections based on "tar" category and menthol inclusion. ⋯ Collectively, the results of these surveys provide evidence that constituent yields are, in general, proportional to "tar" yield and that the relationships between constituent yields and "tar" have remained constant during this time span. Moreover, these data demonstrate that constituent yields of commercially marketed cigarettes available in the U. S. between 1995 and 2000 have been effectively constant.
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Regul. Toxicol. Pharmacol. · Jun 2001
PCBs and neurodevelopmental effects in Michigan children: an evaluation of exposure and dose characterization.
Despite the fact that PCB levels in the general environment have continued to decline over the past decade, concern for potential neurodevelopmental deficits from in utero exposure to these compounds remains unabated. In fact, some regulatory and scientific bodies have concluded that the evidence suggesting that prenatal exposure to PCBs may lead to neurodevelopmental deficits is one of the greatest public health concerns surrounding PCBs. The primary basis for the concern that low-level in utero exposure to PCBs causes neurodevelopmental deficits in children is a series of reports on a cohort of Michigan children presumably exposed to PCBs as a result of their mother's consumption of Great Lakes fish. ⋯ The investigators following these children concluded that they have demonstrated persistent neurodevelopmental effects in this cohort attributable solely to PCBs. However, a detailed analysis of the cohort's exposure characterization, particularly in the initial reports, reveals considerable uncertainty as to the actual exposure status of mothers characterized as "fish eaters" and their offspring. Failure to adequately characterize the PCB exposure of these mothers, or their children, precludes any causal association between in utero exposure to PCBs and neurodevelopmental deficits.
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Regul. Toxicol. Pharmacol. · Apr 2001
Use of human data for the derivation of a reference dose for chlorpyrifos.
In 1998 a panel of experts met to discuss the data available on chlorpyrifos, both human and animal, and to determine the most appropriate endpoints to be used for the derivation of the reference dose (RfD). Since that time, additional data have become available on chlorpyrifos from an experimental study involving humans. ⋯ Therefore, Dow AgroSciences, one of the manufacturers of chlorpyrifos, convened a second panel of toxicology and medical experts on June 21, 1999, to consider the presently available scientific literature both published and unpublished on chlorpyrifos and to determine the acute and chronic toxicological RfDs for chlorpyrifos. Four questions were posed to this second panel of experts concerning the available data on chlorpyrifos. (1) Should the RfD for chlorpyrifos be based on acetylcholinesterase (AChE) inhibition or butyrylcholinesterase (BuChE) inhibition as an endpoint for adverse effect? (2) Should the RfDs for chlorpyrifos be based on the data set from three human studies, which are supported by animal data? (3) Should the FQPA safety factor be reduced to 1xbased on animal studies of pre- or postnatal toxicity? (4) If an RfD for chlorpyrifos were to be based on animal data, then is a 10-fold interspecies uncertainty factor necessary? The panel of experts concluded that: (1) inhibition of BuChE is not an adverse effect, and the RfD for chlorpyrifos should be based on AChE inhibition; (2) the RfD for chlorpyrifos should be based on the three available human studies, which are also supported by animal data; (3) the extra FQPA safety factor should be reduced to 1x, because chlorpyrifos shows no pre- or postnatal toxicity of concern at relevant human exposure conditions; and (4) the extra 10-fold safety factor for interspecies variation appears overly conservative because no differences in species sensitivity to chlorpyrifos is evident.