The literature on the use of solid-phase extraction (SPE) as a tool for trace-element speciation is highly significant. Among methods of pretreatment, SPE is unique because of its effectiveness, robustness, speed and, above all, its "greenness".We illustrate the combination of SFE with highly sensitive detection methods for accurate measurements of chemical species at extremely low concentrations in environmental samples with special reference to aqueous solutions. We examine the analytical strategies for speciation of elements in terms of limits of detection. 2011 Elsevier Ltd. All rights reserved.

BACKGROUND:Analysis of the literature for nonsteroidal anti-inflammatory drugs (NSAIDs) suggests that a low incidence of developmental anomalies occurs in rats given NSAIDs on specific days during organogenesis. Aspirin (acetylsalicylic acid [ASA]), an irreversible cyclooxygenase 1 and 2 inhibitor, induces developmental anomalies when administered to Wistar rats on gestational day (GD) 9, 10, or 11 (Kimmel CA, Wilson JG, Schumacher HJ. Teratology 4:15-24, 1971). There are no published ASA studies using the multiple dosing paradigm of GDs 6 to 17. Objectives of the current study were to compare results between Sprague-Dawley (SD) and Wistar strains when ASA is administered on GD 9, 10, or 11; to compare the malformation patterns following single and multiple dosings during organogenesis in SD rats; and to test the hypothesis that maternal gastrointestinal toxicity confounds the detection of low incidence malformations with ASA when a multiple dosing paradigm is used.METHODS:ASA was administered as a single dose on GD 9 (0, 250, 500, or 625 mg/kg), 10 (0, 500, 625, or 750 mg/kg), or 11 (0, 500, 750, or 1000 mg/kg) and from GD 6 to GD 17 (0, 50, 125, or 250 mg/kg a day) in the multiple dose study to SD rats. Animals were killed on GD 21, and fetuses were examined viscerally.RESULTS:The literature evaluation suggested that NSAIDs induce ventricular septal defects (VSDs) and midline defects (MDs) in rats and diaphragmatic hernia (DH), MDs, and VSDs in rabbits (Cook JC et al., 2003); hence, the present study focused on these malformations, even though ASA induces several other low-incidence malformations. In single dose studies, DH, MD, and VSD were induced on GDs 9 and 10. VSD also was noted following treatment on GD 11. In contrast, DH and MD were noted in the multiple dose study design only in the high-dose group, and VSD was noted across all dose groups.CONCLUSIONS:High concordance in major developmental anomalies between Wistar and SD rats were noted with the exception of VSD in the SD rats and hydrocephalus in the Wistar rats. Variations and malformations were similar when ASA was administered as a single dose or during the period of organogenesis (GDs 6 to 17). It was also evident that, by titrating the dose to achieve a maximum tolerated dose, malformations that normally occur at low incidence, as reported from previous single dose studies, could also be induced with ASA given at multiple doses.

BACKGROUND:A review of the nonsteroidal anti-inflammatory drug (NSAID) literature suggested occurrences of low-level incidences of cardiovascular and midline defects in rabbit fetuses exposed in utero. Aspirin (acetylsalicylic acid, ASA) is a widely used NSAID that irreversibly inhibits cyclooxygenases (COXs) 1 and 2. ASA has been studied extensively in rats and has consistently increased low-incidence cardiovascular malformations and defects in midline closure. The objectives of the current study were to comprehensively define the developmental toxicology profile of ASA in rabbits by using a dosing paradigm encompassing the period of organogenesis and to test the hypothesis that maternal gastrointestinal toxicity after repeated dose administrations hampers the detection of low-incidence malformations with ASA in rabbits by limiting ASA administration to sensitive windows for cardiovascular development and midline closure.METHODS:ASA was administered to pregnant New Zealand White rabbits from gestation days (GDs) 7 to 19 at dose levels of 125, 250, and 350 mg/kg per day and as single doses of 500, 750, or 1000 mg/kg on GD 9, 10, or 11. Cesarean sections were performed on GD 29, and the fetuses were examined for external, visceral and skeletal development.RESULTS:In the repeated dose study, maternal toxicity was exhibited in the 250- and 350-mg/kg per day groups by mortality and decreased food consumption and body weight gain. In the single dose studies, maternal toxicity was exhibited at all doses by reductions in body weight gain and food consumption for 3 days after treatment. Fetal body weight was significantly reduced in the repeated dose study at 350 mg/kg per day. Fetal weights were not affected by single doses of ASA on GD 9, 10, or 11. There were no treatment-related external, visceral or skeletal malformations associated with ASA administration throughout organogenesis or with single doses administered during critical developmental windows.CONCLUSION:These findings supported previous work demonstrating that ASA is not teratogenic in rabbits, as opposed to rats, even when large doses are administered on single days during specific windows of development.