A B S T R A C T :Studies were conducted to determine the comparative effects of tocopherols and tocotrienols on normal mammary epithelial cell growth and viability. Cells isolated from midpregnant BALB/c mice were grown within collagen gels and maintained on serum-free media. Treatment with 0‐120 µM αand γ-tocopherol had no effect, whereas 12.5‐100m µM tocotrienol-rich fraction of palm oil (TRF), 100‐120 µM δ-tocopherol, 50‐60 µM α-tocotrienol, and 8‐14 µM γ- or δ- t o c o t r i e n o l significantly inhibited cell growth in a dose-responsive manner. In acute studies, 24-h exposure to 0‐250 µM α-, γ-, and δ-tocopherol had no effect, whereas similar treatment with 100‐250 µM TRF, 140‐250 µM α-, 25‐100 µM γ- or δ-tocotrienol significantly reduced cell viability. Growth-inhibitory doses of TRF, δ-tocopherol, and a-, γ-, and δ-tocotrienol were shown to induce apoptosis in these cells, as indicated by DNA fragmentation. Results also showed that mammary epithelial cells more easily or preferentially took up tocotrienols as compared to tocopherols, suggesting that at least part of the reason tocotrienols display greater biopotency than tocopherols is because of greater cellular accumulation. In summary, these findings suggest that the highly biopotent γ- and δ- t o c o t r i e n o l isoforms may play a physiological role in modulating normal mammary gland growth, function, and remodeling. Paper no. L8332 in Lipids 35,171‐180 (February 2000).
Human exposure to boron occurs primarily through diet and drinking water sources. Animal studies have found that reduced fetal weight following gestational exposure to boron (as boric acid) is the most sensitive toxicological effect. However, recent studies suggest that newborns in areas with elevated boron in drinking water may receive levels of exposure that exceed the U.S. EPA oral reference dose for B. Currently, there are no data to inform a boron risk assessment accounting for this developmental window. To address this knowledge gap, the National Toxicology Program evaluated developmental toxicity following pre- and postnatal boron exposure. Time-mated female Sprague Dawley (Hsd: Sprague Dawley SD) rats were administered 0-20 mg B/kg/day (as boric acid) via gavage from gestation day 6 to 21; offspring were dosed via gavage at the same respective dose level from postnatal day (PND) 1 to 28. There were no dose-related effects on dam bodyweight, bodyweight gain, or feed consumption. Clinical findings were limited to low incidences of umbilical hernia in the 20 mg B/kg pups which resolved by study completion. Pup plasma boron concentrations increased in dose-proportional manner and were similar between PND 4 and PND 28. Postnatal weight gain was significantly reduced at 20 mg B/kg, with male and female pups weighing 23% less than the controls on PND 28. These findings demonstrate that postnatal growth in the Sprague Dawley rat is sensitive to boron exposure and highlights the importance of evaluating the potential toxicity of agents with known human exposures during early life stages.
Early deaths of young or juvenile animals (before sexual maturation is achieved) in routine regulatory safety studies present pathologists and toxicologists with the challenge of interpreting findings in the male reproductive tract. Additionally, the advent of toxicity testing regulations has resulted in a growing need for the use of juvenile animals in toxicology studies. Here, we present the reproductive toxicity findings from a 13-week inhalation toxicity study with ortho-phthalaldehyde (OPA) in male rats and mice as a case example for working through this challenging task. In this study with OPA, survival was significantly reduced in the two highest exposure concentrations of OPA tested. Early deaths and histopathological lesions in the testes and epididymides were generally also limited to these two highest exposure groups. Therefore, there was concern that peripubertal morphological features could be a confounding factor for the histopathological evaluation of exposure-related testicular and epididymal findings. Although it can be difficult to differentiate exposure-related effects from the normal morphological features defining peripubertal changes in the testes and epididymides in animals that die early in a toxicity study, the use of age-matched controls in this case study with OPA provided a reference and aided in the differentiation of these effects.
This chapter explores the insights gained by a group of teachers from their lived experience as e-learners participating in a blended module on designing e-learning. An understanding of the student perspective on online learning was obtained, but we were also able to reflect on our participation in the module on the basis of our other roles: as teachers and potential e-tutors, and as course designers. As a result, important considerations were identified for the design and facilitation of online courses. These include the support provided to online learners, particularly over the first few weeks; appropriate assessment methods; the facilitation of online collaboration; access to the Internet; time management; and contextualising and scaffolding learning activities. Some issues relating to the implementation of effective e-learning in higher education institutions were also considered. Our lived experience as e-learners was invaluable to our development as e-tutors and module designers, and this approach is strongly recommended to achieve effective learning on how to be an effective online tutor and facilitator and how to design and develop online programmes and activities that make full use of the strengths of online learning.
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