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Seven phthalate esters, representing a variety of chain lengths and degrees of branching in the alcohol moiety, were tested for their ability to produce peroxisome proliferation in the Fischer 344 rat. Di(2-ethylhexyl)adipate (DEHA) was tested using the same protocol and di(2-ethylhexyl)phthalate (DEHP) was run with each study as an internal control. Each ester was administered in the feed for a period of 21 days at levels of 2.5%, 1.2% and either 0.6% or 0.3%. DEHP and DEHA were also fed at levels of 0.1% and 0.01%. The animals were sacrificed and samples of liver were prepared for both light and electron microscopy. Serum samples were assayed for both triglyceride and cholesterol. The remaining portion of the liver was homogenized and assayed for cyanide-insensitive palmitoyl-CoA oxidation, lauric acid 11-hydroxylase and lauric acid 12-hydroxylase. The results show that there is approximately a ten-fold difference between the weakest and strongest esters in terms of their potency to induce changes in relative liver weight and in several of the biochemical parameters. In general, the longer chain esters were more potent than the shorter chain ones, and branched chain esters seemed more potent than straight. Several statistical analyses of the dataset have been performed and all render similar conclusions. The results of one of these evaluations are presented elsewhere in this volume (Lin, 1987).

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We describe here a novel and effective structure to support the replacement of traditional recitation sections in a large upper level biochemistry course with small student-led problem-based learning (PBL) groups ("workshops") that employ a cooperative learning approach. This is part of an ongoing campuswide effort to establish and maintain such workshops as a viable and integral component of many undergraduate courses at the University of Rochester. In biochemistry, for each workshop group of 8 -10 students, we rely on a student leader, usually recruited from the previous year's pool of top students, whose function is both to guide and to inspire the group effort. A crucial component of our approach is that these leaders participate in a semester-long credit-bearing training course co-taught by the course instructors and an educational specialist. In this course, leaders review the preceding and upcoming weeks' workshops and study selected aspects of learning theory, group dynamics, and diversity training. Overall our workshop leaders feel that they benefit substantially from this training by improving their pedagogical skills in the context of biochemistry, by putting theories about group leadership and learning into practice, and by solidifying their working biochemical knowledge. We believe that the important features of implementing our model (the incorporation of a problem-based learning approach into a student-led small group format) are: 1) the teamwork as co-equals between the course instructors and the educational specialists, 2) the concurrent iterative training of the workshop leaders in a credit-bearing course of study, 3) the built-in leader turnover (normally a frustrating occurrence) as a beneficial component of the course, and 4) the enthusiasm and commitment to biochemistry displayed to current students by their peer leaders.Keywords: PBL workshops, peer-leader training, educational partnership, teaching biochemistry, upper level undergraduate courses.At the University of Rochester over the past 3 years, we have replaced traditional weekly recitations in a large college level introductory biochemistry course with small cooperative learning groups. These "workshops," as we call them, employ a problem-based learning (PBL) 1 format with groups of 8 -10 students meeting weekly for 2 h to solve descriptive biochemistry problems in a cooperative learning context. We have also found that the effectiveness of our workshops has been greatly improved by having a skilled leader present to facilitate inquiry and promote uniform participation in contrast to a "leaderless" PBL format that may be appropriate in other situations. There are a number of administrative and pedagogical challenges involved in this type of undertaking, not the least of which is the dual requirement for an increased number of leaders (both a recruitment and a budgetary hurdle) and the need for training that prepares leaders to facilitate workshops effectively. We describe here our solutions to these problems, which also yielded sever...

1. The hydrolysis of di(2-ethylhexyl) terephthalate (DEHT) and di(2-ethylhexyl) phthalate (DEHP) were studied using rat gut homogenate fractions in vitro. Both isomers were hydrolysed by the intestinal fraction; however, DEHP was hydrolysed to 2-ethylhexanol (2-EH) and mono(2-ethylhexyl) phthalate (MEHP) in about equal proportions, whereas DEHT was hydrolysed to 2-EH and terephthalic acid (TPA). The half-lives for disappearance of the diesters were determined to be 12.6 min for DEHP and 53.3 min for DEHT. 2. The absorption and metabolism of DEHT were studied by administering [hexyl-2-14C]DEHT (in corn oil) by oral gavage at a dose level of 100 mg/kg to 10 adult male Sprague-Dawley rats. Urine, faeces and expired air were collected for 144 h and analysed for the presence of radioactivity, and faeces and urine were analysed for unlabelled metabolites. 3. Radioactivity was eliminated in faeces (56.5 +/- 12.1% of dose) primarily as unchanged DEHT, small amounts of MEHT and polar metabolites; excreted in urine (31.9 +/- 10.9% of dose) principally as MEHT and metabolic products of 2-EH; and expired as 14CO2 (3.6 +/- 0.9% of dose). Less than 2% of the administered radioactivity was found in the carcass. Small amounts of 14C were found in the tissues with the highest amounts found in liver and fat. 4. Metabolites identified in urine included terephthalic acid (equivalent to 51% of dose), oxidized metabolites of 2-EH and MEHT, and glucuronic and sulphuric acid conjugates (equivalent to about 10% of dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Eight phthalate esters, with alcohol chain lengths of 1–11 carbon atoms and with various degrees of branching, were tested in vitro in the L5178Y mouse lymphoma mammalian cell mutation assay and in the Balb/3T3 cell transformation assay. The tests were performed as part of a voluntary testing agreement between the Chemical Manufacturers Association’s Phthalate Esters Panel and the United States Environmental Protection Agency (US EPA). The esters tested were: dimethyl phthalate (DMP), di‐n‐butyl phthalate (DBP), butyl benzyl phthalate (BBP), di‐{n‐hexyl, n‐octyl, n‐decyl} phthalate (610P), di‐isononyl phthalate (DINP), di‐{heptyl, nonyl, undecyl} phthalate (711P), di‐isodecyl phthalate (DIDP) and di‐undecyl phthalate (DUP). Both DMP and DBP were found to produce significant increases in the mutant frequency in the mouse lymphoma assay in the presence but not in the absence of an Aroclor‐induced rat liver activation system (S‐9). Ester 610P gave equivocal results in the mouse lymphoma assay in the presence and absence of rat liver S‐9. There was no indication of mutagenic potential for any of the other test materials in the mouse lymphoma assay, and none of the test materials increased transformation frequency in the Balb/3T3 cell transformation assay. Aldehyde metabolites of the de‐esterified alcohols are postulated to play a role in the positive results for DMP and DBP. Copyright © 2000 John Wiley & Sons, Ltd.

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