Family-Integrated Neonatal Music Therapy: A Descriptive Pilot Study of Parental Perceptions on Music Therapy Participation and Long-Term Influences.

Purpose: Following a family-integrated music therapy (MT) approach, describe parental perceptions on the use of music with maternal voice to soothe and connect with the infant and the long-term influence of this approach on parents' integration of music postdischarge. Design: In this descriptive, observational within-subjects pilot cohort study, board-certified music therapists instructed and recorded mothers in singing selected songs of kin. Infants received the recorded sessions weekly from enrollment to discharge. Parents were surveyed at 1- and 6-year postdischarge. Sample: Medically stable preterm infants (n = 12) and their English-speaking parents (n = 17). Main Outcome Variable: Parent perceptions on participation and long-term influence on family integration of music during hospitalization and postdischarge. Results: Parents reported knowledge of soothing and interacting with their children as the highest benefit of MT. They also perceived the effects of an easier transition home, enhanced learning and child development, and personal benefits of positive mood and enhanced relaxation.

Toward a holistic approach to EdTech effectiveness: Lessons from Covid-19 research in Bangladesh, Ghana, Kenya, Pakistan, and Sierra Leone.

During school closures prompted by the Covid-19 pandemic, educational technology (EdTech) was often used to continue educational provision. In this article, we consider EdTech effectiveness using a holistic framework, and synthesise findings from 10 primary research studies of EdTech interventions conducted in low- and middle-income countries during the pandemic. The framework includes five main lenses: learning outcomes, enhancing equity, implementation context, cost and affordability, and alignment and scale. While in-person schooling has largely resumed, there continues to be further integration of EdTech into education systems globally. This analysis provides evidence-based insights and highlights knowledge gaps to shape holistic analysis of both EdTech mainstreaming and future research into the effective use of EdTech to strengthen learning.

An exploration of clinical variables that enhance therapeutic alliance in patients seeking care for musculoskeletal pain: A mixed methods approach.

INTRODUCTION/OBJECTIVES: Therapeutic alliance (TA) is an integral part of building a patient and clinician relationship. TA begins at the initial encounter; however, the specific TA behavioural practices that are most impactful and linked to pain reduction and improved function remain unclear. The primary objective of this study was to explore physical therapist behaviours and interactions during the initial physical therapy evaluation and how they related to the patient's perception of TA. A secondary objective was to explore the relationship between TA, pain intensity, and function. METHODS: A mixed methods study was conducted. Pain intensity, TA and self-reported function were assessed at three time points. Spearman's Rho (ρ) was used to quantify if there was an association between increased TA and function and reduced pain intensity, while a checklist of TA themes and behavioural practices was used for the qualitative analysis. RESULTS: There was a statistically significant negative correlation between patient-perceived TA and pain intensity immediately after the initial evaluation (ρ = -0.39 [p = 0.048]). Behavioural practices associated with higher TA included information gathering, pausing to listen, using humour and transitions, and use of clarifying questions. Behavioural practices associated with patient-perceived lower TA interactions were lack of touch, the absence of pain neuroscience education, and not restating what the patient said during the interview. CONCLUSION: This study highlights a relationship between TA and reduction of pain intensity after the initial evaluation and identifies key behavioural practices that could positively and negatively impact TA during the clinical encounter.

More Than 1 in 3 Patients With Chronic Low Back Pain Continue to Use Opioids Long-term After Spinal Fusion: A Systematic Review.

OBJECTIVE: A common expectation for patients after elective spine surgery is that the procedure will result in pain reduction and minimize the need for pain medication. Most studies report changes in pain and function after spine surgery, but few report the extent of opioid use after surgery. This systematic review aims to identify the rates of opioid use after lumbar spine fusion. MATERIALS AND METHODS: PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and Ovid Medline were searched to identify studies published between January 1, 2005 and June 30, 2020 that assessed the effectiveness of lumbar fusion for the management of low back pain. RESULTS: Of 6872 abstracts initially identified, 329 studies met the final inclusion criteria, and only 32 (9.7%) reported any postoperative opioid use. Long-term opioid use after surgery persists for more than 1 in 3 patients with usage ranging from 6 to 85.9% and a pooled mean of 35.0% based on data from 21 studies (6.4% of all lumbar fusion studies). DISCUSSION: Overall, opioid use is not reported in the majority of lumbar fusion trials. Patients may expect a reduced need for opioid-based pain management after surgery, but the limited data available suggests long-term use is common. Lack of consistent reporting of these outcomes limits definitive conclusions regarding the efficacy of spinal fusion for reducing long-term opioid. Patient decisions about undergoing surgery may be altered if they had realistic expectations about rates of postsurgical opioid use. Spine surgery trials should track opioid utilization out to a minimum of 6 months after surgery as a core outcome.

"Seeing" Data Like an Expert: An Eye-Tracking Study Using Graphical Data Representations.

Given the centrality of data visualizations in communicating scientific information, increased emphasis has been placed on the development of students' graph literacy-the ability to generate and interpret data representations-to foster understanding of domain-specific knowledge and the successful navigation of everyday life. Despite prior literature that identifies student difficulties and methods to improve graphing competencies, there is little understanding as to how learners develop these skills. To gain a better resolution of the cognitive basis by which individuals "see" graphs, this study uses eye tracking (ET) to compare the strategies of non-science undergraduates (n = 9), early (n = 7) and advanced (n = 8) biology undergraduates, graduate students (n = 6), and science faculty (n = 6) in making sense of data displays. Results highlight variation in how individuals direct their attention (i.e., fixations and visual search patterns) when completing graph-based tasks as a function of science expertise. As research on the transition from novice to expert is crucially important in understanding how we might design curricula that help novices move toward more expert-like performance, this study has implications for the advancement of new strategies to aid the teaching and learning of data analysis skills.

An ultra-microporous organic polymer for high performance carbon dioxide capture and separation.

Rational design concepts were used to prepare a novel porous benzimidazole-linked polymer (BILP-101) in a simple one-pot reaction. BILP-101 has exhibited ultra-microporosity (0.54 nm), very high CO2 uptake (∼1 mmol g(-1), 4 wt%, 0.15 bar/298 K) and exceptional CO2/N2 selectivity of 80 (298 K), which results in remarkable working capacity and regenerability for CO2 capture applications.

Impact of Varying the Parameters of Stimulation of 2 Commonly Used Waveforms on Muscle Force Production and Fatigue.

STUDY DESIGN: Laboratory-based experimental study using a repeated-measures design. OBJECTIVES: To determine the effect of varying stimulation parameters of burst-modulated alternating current (BMAC) and pulsed current (PC) on quadriceps femoris muscle force output and fatigue. BACKGROUND: The impact of altering stimulation parameters on muscle force and fatigue using PC has been well described; however, less is known regarding BMAC. METHODS: Quadriceps femoris muscle force was measured during a series of neuromuscular electrical stimulation-induced muscle contractions, with varying combinations of pulse duration and frequency, using PC or varying duty cycles and burst frequencies using BMAC. Additionally, muscle fatigue tests were conducted bilaterally with different stimulation waveforms and parameters. RESULTS: For PC, the product of pulse duration and frequency was strongly predictive of muscle force output (R(2) = 0.85, P<.05). When using BMAC, the duty cycle was a strong predictor of force output (R(2) = 0.91, P<.05). Altering the frequency during BMAC had no effect on muscle force production, as opposed to the classic force-frequency relationship consistently observed with PC. Waveform type significantly impacts muscle fatigue, the BMAC resulted in a more rapid rate of fatigue irrespective of stimulation frequency, and it was confirmed again that lower frequencies of PC result in less fatigue during repeated muscle contractions. CONCLUSION: In this study, altering the burst frequency of BMAC did not influence muscle force or fatigue, whereas the duty cycle significantly impacted muscle force production. Frequency of PC impacted both force and fatigue as expected, demonstrating increased muscle force and fatigue with increased frequency.

Theoretical and experimental studies of CO2 and H2 separation using the 1-ethyl-3-methylimidazolium acetate ([emim][CH3COO]) ionic liquid.

The performance of [emim][CH(3)COO] ionic liquid (IL) to separate mixtures of CO(2) and H(2) is studied using both classical and ab initio simulation methods and experiments. Simulations show that H(2) solubility and permeability in [emim][CH(3)COO] are quite low with Henry's law constants about 1 × 10(4) bar and permeabilities in the range 29-79 barrer at 313-373 K. In the case of CO(2) absorption in [emim][CH(3)COO], ab initio molecular dynamics simulations predict two types of CO(2) absorption states. In type I state, CO(2) molecules interact with the [CH(3)COO](-) anion through strong complexation leading to high CO(2) solubility. The C atom of CO(2) is located close to the O atoms of the [CH(3)COO](-) anion with an average distance of about 1.61 Å. The CO(2) bond angle (θ(OCO)) is about 138°, significantly perturbed from that of an isolated linear CO(2). In type II state, the CO(2) molecule maintains a linear configuration and is located at larger separations (>2.2 Å) from the [CH(3)COO](-) anion. The weaker interaction of CO(2) with the [CH(3)COO](-) anion in type II state is similar to the one observed when CO(2) absorbs in [bmim][PF(6)]. Simulations further demonstrate that the [emim](+) cation competes with CO(2) to interact with the [CH(3)COO](-) anion. The predicted high CO(2) permeability and low H(2) permeability in [emim][CH(3)COO] are also verified by our experiments. The experimental CO(2) permeability in [emim][CH(3)COO] is in the range of 1325-3701 barrer, and high experimental CO(2)/H(2) permeability selectivities of 21-37 at 313-373 K are observed. We propose that by replacing [emim](+) cation with 1-butyl-1-methylpyrrolidinium ([PY(14)](+)) further enhancement of CO(2) solubility in [PY(14)][CH(3)COO] IL will be obtained as well as good performance to separate CO(2) and H(2).

Validation of the intact rat weanling uterotrophic assay with notes on the formulation and analysis of the positive control chemical in vehicle.

The intact female weanling version in the Organization for Economic Cooperation and Development (OECD) uterotrophic assay Test Guideline (TG) 440 is proposed as an alternative to the adult ovariectomized female version, because it does not involve surgical intervention (vs the ovariectomized version) and detects direct/indirect-acting estrogenic/anti-estrogenic substances (vs the ovariectomized version which detects only direct-acting estrogenic/anti-estrogenic substances binding to the estrogen receptor). This validation study followed OECD TG 440, with six female weanling rats (postnatal day 21) per dose group and six treatment groups. Females were weighed and dosed once daily by oral gavage for three consecutive days, with one of six doses of 17α-ethinyl estradiol in corn oil at 5 ml kg⁻¹ at 0 and 0.1-10 µg kg⁻¹ per day. On postnatal day 24, the juvenile females were euthanized by CO2 asphyxiation, weighed, livers weighed and uteri weighed wet and blotted. The presence or absence of vaginal patency was recorded. Absolute and relative (to terminal body weight) uterine wet and blotted weights and uterine luminal fluid weights were significantly increased at 3.0 and 10.0 (both P < 0.01) µg kg⁻¹ per day, and increased to ~140% of control values at 1.0 µg kg⁻¹ per day (not statistically significantly). In vivo body weights, weight changes, feed consumption, liver weights and terminal body weights were unaffected. Vaginal patency was not acquired in any female at any dose, although vaginal puckering was observed in one female at 10.0 µg kg⁻¹ per day. Therefore, this intact weanling uterotrophic assay is validated in our laboratory for use under US and European endocrine toxicity testing programs/legislation.

Metabolomics in the assessment of chemical-induced reproductive and developmental outcomes using non-invasive biological fluids: application to the study of butylbenzyl phthalate.

This study was conducted to evaluate the use of metabolomics for improving our ability to draw correlations between early life exposures and reproductive and/or developmental outcomes. Pregnant CD rats were exposed by gavage daily during gestation to vehicle or to butylbenzyl phthalate (BBP) in vehicle at a level known to induce effects in the offspring and at a level previously not shown to induce effects. Urine was collected for 24 h (on dry ice using all glass metabolism chambers) from dams on gestational day 18 (during exposure) and on post natal day (pnd) 21, and from pnd 25 pups. Traditional phenotypic anchors were measured in pups (between pnd 0 and pnd 26). Metabolomics of urine collected from dams exposed to vehicle or BBP exhibited different patterns for endogenous metabolites. Even three weeks after gestational exposure, metabolic profiles of endogenous compounds in urine could differentiate dams that received the vehicle, low dose or high dose of BBP. Metabolic profiles could differentiate male from female pups, pups born to dams receiving the vehicle, low or high BBP dose, and pups with observable adverse reproductive effects from pups with no observed effects. Metabolites significant to the separation of dose groups and their relationship with effects measured in the study were mapped to biochemical pathways for determining mechanistic relevance. The application of metabolomics to understanding the mechanistic link between low levels of environmental exposure and disease/dysfunction holds huge promise, because this technology is ideal for the analysis of biological fluids in human populations.

Two-generation reproductive toxicity study of dietary bisphenol A in CD-1 (Swiss) mice.

Dietary bisphenol A (BPA) was evaluated in a mouse two-generation study at 0, 0.018, 0.18, 1.8, 30, 300, or 3500 ppm (0, 0.003, 0.03, 0.3, 5, 50, or 600 mg BPA/kg/day, 28 per sex per group). A concurrent positive control group of dietary 17beta-estradiol (0.5 ppm; 28 per sex) confirmed the sensitivity of CD-1 mice to an endogenous estrogen. There were no BPA-related effects on adult mating, fertility or gestational indices, ovarian primordial follicle counts, estrous cyclicity, precoital interval, offspring sex ratios or postnatal survival, sperm parameters or reproductive organ weights or histopathology (including the testes and prostate). Adult systemic effects: at 300 ppm, only centrilobular hepatocyte hypertrophy; at 3500 ppm, reduced body weight, increased kidney and liver weights, centrilobular hepatocyte hypertrophy, and renal nephropathy in males. At 3500 ppm, BPA also reduced F1/F2 weanling body weight, reduced weanling spleen and testes weights (with seminiferous tubule hypoplasia), slightly delayed preputial separation (PPS), and apparently increased the incidence of treatment-related, undescended testes only in weanlings, which did not result in adverse effects on adult reproductive structures or functions; this last finding is considered a developmental delay in the normal process of testes descent. It is likely that these transient effects were secondary to (and caused by) systemic toxicity. Gestational length was increased by 0.3 days in F1/F2 generations; the toxicological significance, if any, of this marginal difference is unknown. At lower doses (0.018-30 ppm), there were no treatment-related effects and no evidence of nonmonotonic dose-response curves for any parameter. The systemic no observable effect level (NOEL) was 30 ppm BPA (approximately 5 mg/kg/day); the reproductive/developmental NOEL was 300 ppm (approximately 50 mg/kg/day). Therefore, BPA is not considered a selective reproductive or developmental toxicant in mice.

One-generation reproductive toxicity study of dietary 17beta-estradiol (E2; CAS No. 50-28-2) in CD-1 (Swiss) mice.

There is no information on reproductive/developmental effects in mice from dietary estrogen. Therefore, 10 adult CD-1 mice/sex/group were administered dietary 17beta-estradiol (E2) at 0, 0.005, 0.05, 0.5, 2.5, 5, 10, and 50 ppm for 2-week prebreed, mating, gestation, lactation. F1 weanlings (3/sex/litter) were necropsied and 2/sex/litter were retained, with exposure, until vaginal patency (VP) or preputial separation (PPS) and then necropsied. Results included complete infertility at 2.5-50 ppm with normal mating indices. At 0.5 ppm (and above), F0 adult female uterus plus cervix plus vagina weights (UCVW) were increased. At 0.5 ppm: prolonged gestational length; increased F1 stillbirth index; reduced live birth index and litter size; decreased testes and epididymides weights at weaning; unaffected AGD on pnd 0 and 21; delayed PPS; increased undescended testes; unaffected prostate weight; accelerated VP; enlarged vaginas; fluid-filled uteri. At 0.05 ppm: no F0 reproductive effects, increased F1 weanling UCVW; delayed PPS. The NOEL was 0.005 ppm ( approximately 1 microg/kg/day).

Two-generation reproductive toxicity evaluation of dietary 17beta-estradiol (E2; CAS No. 50-28-2) in CD-1 (Swiss) mice.

No information exists on reproductive/developmental effects in mice exposed to dietary 17beta-estradiol (E2) over multiple generations. Therefore, under OECD Test Guideline 416 with enhancements, CD-1 mice (F0 generation, 25 mice/sex/group) were exposed to dietary E2 at 0, 0.001, 0.005, 0.05, 0.15, or 0.5 ppm ( approximately 0, 0.2, 1, 10, 30, or 100 mug E2/kg body weight/day) for 8 weeks prebreed, 2 weeks mating, approximately 3 weeks gestation, and 3 weeks lactation. At weaning, selected F1 offspring (F1 parents; 25/sex/group) and extra retained F1 males (one per litter) were exposed to the same dietary concentrations and durations as the F0 generation; study termination occurred at F2 weaning; F1/F2 weanlings (up to three per sex per litter) were necropsied with organs weighed. At 0.5 ppm, effects were increased F1/F2 perinatal loss, prolonged F0/F1 gestational length, reduced numbers of F2 (but not F1) litters/group, reduced F1/F2 litter sizes, accelerated vaginal patency (VP) and delayed preputial separation (PPS), increased uterus + cervix + vagina weights (UCVW) in F0/F1 adults and F1/F2 weanlings, and decreased testes and epididymides weights (TEW) in F1/F2 weanlings. At 0.15 ppm, effects were increased UCVW in F0/F1 adults and F1/F2 weanlings, accelerated VP, delayed PPS, and reduced TEW in F1/F2 weanlings. At 0.05 ppm, UCVW were increased in F1/F2 weanlings, and PPS was delayed only in extra retained F1 males. There were no biologically significant or treatment-related effects on F0/F1 parental body weights, feed consumption, or clinical observations, or on F0/F1 estrous cyclicity, F0/F1 andrology, or F1/F2 anogenital distance at any dose. The no observable effect level was 0.005 ppm E2 ( approximately 1 mug/kg/day). Therefore, the mouse model is sensitive to E2 by oral administration, with effects on reproductive development at doses of 10- 100 mug/kg/day.

Prenatal developmental toxicity evaluation of 2',3'-dideoxyinosine (ddI) and 2',3'-didehydro-3'-deoxythymidine (d4T) co-administered to Swiss Albino (CD-1) mice.

BACKGROUND: In pregnant women, antiretroviral drugs improve maternal health and reduce vertical transmission of human immunodeficiency virus to the infant. However, few nonclinical studies have examined the potential for adverse drug interactions. METHODS: On gestational days (GD) 6-16, mice were dosed with vehicle, ddI (360, 1440, or 2,880 mg/kg/day, p.o.), d4T (60, 240, or 480), or ddI/d4T combinations (360/60, 1,440/240, or 2,880/480). Daily doses were divided into two equal parts that were administered >or=6-hr apart. Body weight, clinical signs, and feed consumption were monitored. Pregnancies (22-24/group) were confirmed at necropsy. Maternal liver and gravid uterine weights (GUW), uterine implants (resorption, live or dead fetus), fetal body weight, gender, and morphologic anomalies (external, visceral, skeletal) were recorded. RESULTS: Maternal body weight, clinical signs, and GUW were unaffected. Maternal weight change corrected for GUW was greater than controls at 60 and 480 d4T. Relative feed consumption during treatment was increased relative to controls at 1,440 and 2,880 ddI and 2,880/480 ddI/d4T. Relative maternal liver weight was elevated above controls at 240 and 480 d4T and 2,880/480 ddI/d4T, and above the constituent dose of ddI at 1,440/240 and 2,880/480 ddI/d4T. Liver weight was not affected by ddI and there was no significant drug interaction. Prenatal mortality and morphologic anomalies were not increased. Fetal body weight showed only a decreasing trend for ddI/d4T, no effect for ddI or d4T, and no statistically significant drug interaction. CONCLUSIONS: In pregnant mice, ddI/d4T combinations were not associated with well-defined developmental toxicity or adverse drug interactions.

Three-generation evaluation of dietary para-nonylphenol in CD (Sprague-Dawley) rats.

This study evaluated the potential for dietary para-nonylphenol (NP; CAS No. 84852-15-3) to affect parental fertility and growth and development of three offspring generations in CD (Sprague-Dawley [SD]) rats, including sperm counts across generations to determine the validity of equivocal reductions observed in the F2 generation by R. E. Chapin et al. (1999, Toxicol. Sci. 52, 80-91). Male rat kidney toxicity was also examined based on inconsistent observations in NP-exposed rats at 2000 ppm but not at 200 or 650 ppm in Purina 5002 (H. C. Cunny et al., 1997, Regul. Toxicol. Pharmacol. 26, 172-178) and at all of these NP concentrations in NIH-07 diet (R. E. Chapin et al., 1999, Toxicol. Sci. 52, 80-91). Concentrations were 0, 20, 200, 650, and 2000 ppm NP in Purina 5002 diet and 0 and 650 ppm NP in NIH-07 diet. 17beta-estradiol (E2) was used as a positive control at 2.5 ppm in Purina 5002 diet. There were no NP effects on any reproductive parameters in any generation, including sperm counts. Kidney toxicity (histopathology) occurred at 650 and 2000 ppm with no clear difference for the two diets. Ovarian weight was decreased at 2000 ppm NP in all generations, with no effect on reproduction. Dietary E2 at 2.5 ppm caused renal, reproductive, and developmental (lactational and peripubertal) toxicity in all generations. This study confirmed that dietary NP is not a selective reproductive toxicant with an no observable adverse effect level (NOAEL) of > 2000 ppm ( approximately > 150 mg/kg/day) and provided an NOAEL for male rat kidney toxicity of 200 ppm NP (approximately 15 mg/kg/day).

Developmental toxicity evaluation of berberine in rats and mice.

BACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health-related products. It is a component of goldenseal, an herbal supplement. Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in rats and mice. METHODS: Berberine chloride dihydrate was administered in the feed to timed-mated Sprague-Dawley (CD) rats (0, 3,625, 7,250, or 14,500 ppm; on gestational days [GD] 6-20), and Swiss Albino (CD-1) mice (0, 3,500, 5,250, or 7,000 ppm; on GD 6-17). Ingested doses were 0, 282, 531, and 1,313 mg/kg/day (rats) and 0, 569, 841, and 1,155 mg/kg/day (mice). RESULTS: There were no maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL), based on reduced maternal weight gain, was 7,250 ppm. The rat developmental toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In the mouse study, equivocal maternal and developmental toxicity LOAELs were 5,250 ppm. Due to scattering of feed in the high dose groups, a gavage study at 1,000 mg/kg/day was conducted in both species. CONCLUSIONS: In rats, maternal, but not fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7,250 ppm (531 mg/kg/day) based on the feed study and the developmental toxicity NOAEL was raised to 1,000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of the treated females died. Surviving animals had increased relative water intake, and average fetal body weight per litter decreased 5-6% with no change in live litter size. The maternal toxicity LOAEL remained at 5,250 ppm (841 mg/kg/day) BCD, based on increased water consumption. The developmental toxicity LOAEL was raised to 1,000 mg/kg/day BCD based on decreased fetal body weight.

Postnatal development of rat pups after maternal exposure to diethanolamine.

BACKGROUND: Diethanolamine (DEA), a widely used surfactant, was administered to pregnant mice at the oral LD10 resulting in failure of pups to grow and thrive through postnatal day (PND) 3 [National Toxicology Program, 1987; York et al., Teratology 37:503-504, 1988]. The toxicity profile for DEA differs among rodent species. This study investigated DEA-induced postnatal toxicity in a second species. METHODS: Timed-mated Sprague-Dawley rats were dosed (0, 50, 125, 200, 250, or 300 mg DEA/kg/day, p.o.) on gestational days (GD) 6-19. Dams and pups were monitored for body weight, feed/water intake, clinical signs, litter size, and sex ratio. At necropsy (PND 21), maternal liver and kidney weights and number of uterine implantation sites were recorded. RESULTS: The high-dose group was terminated early due to excessive toxicity. The estimated maternal LD10 was 218 mg/kg/day. Maternal effects included decreased body weight and relative feed intake (>or=200 mg/kg/day), transiently reduced relative water intake (125 and 250 mg/kg/day), and increased absolute kidney weight (>or=125 mg/kg/day). Postimplantation loss (PND 0) and pup mortality (PND 0-4) were increased (>or=200 and >or=125 mg/kg/day, respectively). Pup body weight was reduced (>or=200 mg/kg/day) as late as PND 21. CONCLUSIONS: This study demonstrates reduced postnatal growth and survival in a second species after gestational exposure to DEA, persistence of toxic effects through the end of lactation, possibly due to long elimination half-life, and maternal and developmental toxicity no-observed-adverse-effect level (NOAELs) (50 mg/kg/day) and lowest-observed-adverse-effect level (LOAELs) (125 mg/kg/day) for oral DEA exposure during embryo/fetal development in the rat.

Developmental toxicity evaluation of emodin in rats and mice.

BACKGROUND: Emodin, a widely available herbal remedy, was evaluated for potential effects on pregnancy outcome. METHODS: Emodin was administered in feed to timed-mated Sprague-Dawley (CD) rats (0, 425, 850, and 1700 ppm; gestational day [GD] 6-20), and Swiss Albino (CD-1) mice (0, 600, 2500 or 6000 ppm; GD 6-17). Ingested dose was 0, 31, 57, and approximately 80-144 mg emodin/kg/day (rats) and 0, 94, 391, and 1005 mg emodin/kg/day (mice). Timed-mated animals (23-25/group) were monitored for body weight, feed/water consumption, and clinical signs. At termination (rats: GD 20; mice: GD 17), confirmed pregnant dams (21-25/group) were evaluated for clinical signs: body, liver, kidney, and gravid uterine weights, uterine contents, and number of corpora lutea. Fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations/variations. RESULTS: There were no maternal deaths. In rats, maternal body weight, weight gain during treatment, and corrected weight gain exhibited a decreasing trend. Maternal body weight gain during treatment was significantly reduced at the high dose. In mice, maternal body weight and weight gain was decreased at the high dose. CONCLUSIONS: Prenatal mortality, live litter size, fetal sex ratio, and morphological development were unaffected in both rats and mice. At the high dose, rat average fetal body weight per litter was unaffected, but was significantly reduced in mice. The rat maternal lowest observed adverse effect level (LOAEL) was 1700 ppm; the no observed adverse effect level (NOAEL) was 850 ppm. The rat developmental toxicity NOAEL was > or =1700 ppm. A LOAEL was not established. In mice, the maternal toxicity LOAEL was 6000 ppm and the NOAEL was 2500 ppm. The developmental toxicity LOAEL was 6000 ppm (reduced fetal body weight) and the NOAEL was 2500 ppm.

Reproductive toxicity evaluation of dietary butyl benzyl phthalate (BBP) in rats.

Butyl benzyl phthalate (BBP) was administered in the diet at 0, 750, 3750, and 11,250 ppm ad libitum to 30 rats per sex per dose for two offspring generations, one litter/breeding pair/generation, through weaning of F2 litters. Adult F0 systemic toxicity and adult F1 systemic and reproductive toxicity were present at 11,250 ppm (750 mg/kg per day). At 11,250 ppm, there were reduced F1 and F2 male anogenital distance (AGD) and body weights/litter during lactation, delayed acquisition of puberty in F1 males and females, retention of nipples and areolae in F1 and F2 males, and male reproductive system malformations. At 3750 ppm (250 mg/kg per day), only reduced F1 and F2 offspring male AGD was present. There were no effects on parents or offspring at 750 ppm (50 mg/kg per day). The F1 parental systemic and reproductive toxicity no observable adverse effect level (NOAEL) was 3750 ppm. The offspring toxicity NOAEL was 3750 ppm. The offspring toxicity no observable effect level (NOEL) was 750 ppm, based on the presence of reduced AGD in F1 and F2 males at birth at 3750 ppm, but no effects on reproductive development, structures, or functions.