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Large scale complex systems require monitoring to ensure that they are able to provide continuous services into the future. Existing integrity measurement techniques determine instantaneous measures of whether a system meets its operational parameters which is insufficient as the measure needs to both incorporate the transitory nature of problems as well as locality-based effects. An analysis methodology has been developed that, with an understanding of the composite nature of the system, can provide an indication of the system integrity. This analysis examines the effect of failure events on the operational state of the system. Observed or predicted events are then collected into a summary value that reflects the operational availability of the system combined with durations where the system was in a compromised state. Therefore, the analysis provides an important link between low-level failures and the effect on a system's operation once redundancy and adaptation have taken effect. [ABSTRACT FROM AUTHOR]

Background: For the optimal nutrition of children under 2 years of age, it is considered important that they be exclusively breastfed for the first 6 months before being given complementary food. Aims and Objectives: A cross-sectional nutritional baseline survey was undertaken in 2011 in the Kasungu and Mzimba Districts of Malawi to assess the nutritional status of children under 2 years of age and its determinants in order to prepare a nutrition education intervention programme. The intention of this study was to assess the nutritional status of infants aged 0–<6 months with regard to food intake. Methods: Interviews were conducted on randomly selected families with children under 2 years; anthropometric measurements were obtained from mothers and their children. Only infants between 0 and <6 months were selected for analysis (n = 196). An ANCOVA test was performed on age of the infant with mothers' height and weight as covariates. Results: Prevalence of stunting (infants' length-for-age Z-score (LAZ) <−2SD) was 39%, wasting (WLZ <−2SD) 2%, and underweight (WAZ <−2SD) 13%. Of the infants under 6 months, 43% were exclusively breastfed. Predominant breastfeeding and mixed breastfeeding were less common (21% and 36%, respectively). The ANCOVA confirmed the association between exclusive breastfeeding and LAZ and WAZ: exclusively breastfed infants had a higher mean (SE) LAZ (−1·13, 0·12) and WAZ (−0·41, 0·13) than infants not being exclusively breastfed (−1·59, 0·11, and −0·97, 0·11, respectively). There was no overall significant association between breastfeeding practice and WLZ. Conclusion: Exclusive breastfeeding of infants under 6 months is associated with higher mean LAZ and WAZ. Promotion of exclusive breastfeeding in low-income countries is important in preventing growth retardation. [ABSTRACT FROM AUTHOR]

A simple, new method permitting the simultaneous determination and confirmation of trace residues of 24 different growth promoters and metabolites using liquid chromatography-mass spectrometry was developed and validated. The compounds were extracted from bovine tissue using acetonitrile; sodium sulphate was also added at this stage to aid with purification. The resulting mixture was then evaporated to approximately 1 ml and subsequently centrifuged at high speed and an aliquot injected onto the LC-MS/MS system. The calculated CCα values ranged between 0.11 and 0.46 µg kg−1; calculated CCβ were in the range 0.19–0.79 µg kg−1. Accuracy, measurement of uncertainty, repeatability and linearity were also determined for each analyte. The analytical method was applied to a number of bovine tissue samples imported into Ireland from third countries. Levels of progesterone were found in a number of samples at concentrations ranging between 0.28 and 30.30 µg kg−1. Levels of alpha- and beta-testosterone were also found in a number of samples at concentrations ranging between 0.22 and 8.63 µg kg−1 and between 0.16 and 2.08 µg kg−1 respectively. [ABSTRACT FROM AUTHOR]

Highly efficient red phosphorescent organic light-emitting devices (PHOLEDs) were fabricated using extremely low doping technology in a simple device configuration. They were developed by making use of the narrow-bandgap fluorescent host material bis(10-hydroxybenzo[h] quinolinato)beryllium complex (Bebq2) and red dopant tris(1-phenylisoquinoline)iridium (Ir(piq)3). Maximum current and power efficiencies of 11.60 cd/A and 13.02 lm/W, respectively, are demonstrated with an extremely low doping level of 1 wt%. These results reveal a practical way to make highly efficient PHOLEDs by reducing dopant self quenching. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of the project was to identify characteristics associated with successful re-integration into the community post-inpatient rehabilitation after stroke. A key issue was determining re-integration from the person's perspective, taking into account the person's preferred lifestyle choices. Method. Research design: A prospective exploratory follow up study. Participants: A consecutive sample of 45 participants discharged from IP rehabilitation following stroke and 23 carers associated with the participants. Measures: Goal attainment scaling was utilised to determine successful community integration. Factors that may have contributed to goal achievement were measured prior to discharge and at 6 months post-discharge. Scales used include the Functional Independence Measure, Mini Mental test, the CES-D depression scale and a self-efficacy scale, Strategies Used by People to Promote Health. London Handicap Scale scores and Carer Strain Index were collected at 6 months. Results. Twenty percent of participants achieved all their goals. Significant correlations were observed between goal achievement score and concurrent measures of physical function, depression and self efficacy at 6 months post-discharge. Conclusions. Stroke survivors who achieved their goals were less likely to be depressed, showed stronger self efficacy beliefs and more positive perceptions of their participation in everyday and community life. [ABSTRACT FROM AUTHOR]

A combined repeated-dose toxicity study with reproduction was conducted with 2‐pentenenitrile (2-PN). Rats (10/sex per dose level) were dosed with 2-PN once daily by gavage at dose levels of either 0, 1, 3, or 10 mg kg -1 day -1 for 28 days, prior to and during cohabitation, and through day 3 of lactation. General clinical observations were recorded daily; body weights were recorded weekly. A neurobehavioral evaluation consisting of a functional observational battery and motor activity was conducted in all parental rats (10/sex per group). Clinical pathology parameters (hematology, clinical chemistry, coagulation) were measured in parental rats. Pup weights and clinical signs were recorded at birth and on lactation day 4. Parental rats were given a gross pathological examination, organ weights were obtained, and histological examination was conducted for the control and 10 mg kg -1 day -1 groups. No effects were seen with regard to mortality, clinical signs, functional observational battery and motor activity, hematology, or organ weights. Females receiving 10 mg/kg and males from all dose groups showed lower body weight gains and feed efficiency. Increased albumin concentrations were seen in both sexes given 10 mg/kg. Females in the 10 mg/kg group showed degeneration of the olfactory mucosa. No effects on the numbers of pups born, number surviving to lactation day 4, pup weight, and no gross anatomical development changes were observed. Under the conditions of this study, the no-observed-effect level (NOEL) for systemic toxicity in rats was 3 mg kg -1 day -1 , based on degeneration of olfactory mucosa in females at 10 mg kg -1 day -1 . The NOEL for reproductive and neurobehavioral toxicity in rats and for toxicity to offspring was 10 mg kg -1 day -1 , the highest dose level tested. [ABSTRACT FROM AUTHOR]

Male and female mice, rats, hamsters, and rabbits were treated with a single oral dose of 14 C-ammonium perfluorooctanoate (APFO), and the excretion and tissue distributions were followed for 120 h (168 h in the rabbit). Substantial sex and species differences in the excretion and disposition of 14 C-radioactivity derived from 14 C-labeled APFO were observed in this study. The female rat and the male hamster excreted more than 99% of the original 14 C activity by 120 h after dosing; conversely, the male rat and the female hamster excreted only 39% and 60% of the original 14 C activity, respectively, by 120 h postdosing. The male and female rabbits excreted the 14 C activity as rapidly and completely as the female rat and the male hamster, whereas male and female mice excreted only 21% of the original 14 C activity by 120 h postdosing. The rapid excretors (female rat, male hamster, and male and female rabbits) contained negligible amounts of 14 C in organs and tissues at sacrifice. The slow excretors exhibited the highest 14 C concentrations in the blood and liver followed by the kidneys, lungs, and skin. [ABSTRACT FROM AUTHOR]

The potential maternal and developmental toxicity of 8-2 Telomer B Alcohol was assessed in rats. Groups of 22 time-mated female Crl:CD (SD)IGS BR rats were administered oral gavage doses as suspensions of 8-2 Telomer B Alcohol in aqueous 0.5% methylcellulose from day 6 through 20 of gestation (G) at daily doses of either 0, 50, 200, or 500 mg/kg. Under the conditions of this study, adverse maternal toxicity was produced at 500 mg kg - 1 day - 1 and consisted of maternal mortality, decreased body weights and body weight gains, and increased clinical observations of toxicity. One litter at 500 mg kg - 1 day - 1 consisted of one early resorption and was believed to be secondary to overt maternal toxicity, although single conceptus litters occur historically in this strain of rats. Developmental toxicity at 500 mg kg - 1 day - 1 consisted of increased fetal skeletal variations (delayed pelvic bone ossification and wavy ribs). At 200 and 500 mg kg - 1 day - 1 , there were transient reductions in maternal feed consumption. In addition, there were slight increases in the incidence of delayed fetal skull bone ossification at 200 and 500 mg kg - 1 day - 1 . The no-observed-adverse-effect level (NOAEL), defined as the highest dose at which adverse effects attributable to the test substance were not detected, for both maternal and developmental toxicity, is considered to be 200 mg kg - 1 day - 1 . Thus, 8-2 Telomer B Alcohol is not considered to be a selective developmental toxicant in rats. The transient and quantitative nature of the observations in the 200 mg/kg group supports the conclusion that these findings were not adverse. [ABSTRACT FROM AUTHOR]

Rat and human epidermal membranes were mounted onto in vitro diffusion cells with an exposure area of 0.64 cm², and skin integrity was confirmed using electrical impedance. Following membrane selection, Fluorad FC-118, a 20% aqueous solution of ammonium perfluorooctanoate (AFPO), was applied to the epidermal surface of each skin replicate at approximately 150 μL/cm² and the donor chamber opening occluded with Paraflim. Serial receptor fluid samples were collected hourly from 1 to 6 h and at 12, 24, 30, and 48 h and analyzed by liquid chromatography-mass spectrometry (LC- MS) for APFO anion (PFO-). For rat skin, the time to steady-state penetration (6500 ± 3000 ng APFO · cm² · h-1) occurred in less than 12 h, which was sustained until termination (48 h). Based on the concentration of the applied test material, the permeability coefficient (Kp) for APFO in rat skin was calculated to be 3.25 ± 1.51 x 10-5 cm/h. By end of the 48-h exposure period, only a small portion of the total APFO applied (1.44 ± 1.13%) had penetrated through rat skin. For human skin, steady-state penetration of APFO (190 ± 57 ng APFO · cm-2 · h-1) was reached by 12 h. Based on the concentration of the applied test material, the permeability coefficient for APFO in human skin was calculated to be 9.49 ± 2.86 x 10-7 cm/h. By the end of the 48-h exposure period, only a negligible amount of the total APFO applied (0.048 ± 0.0 1%) had penetrated through human skin. Thus, under infinite dose and occlusive conditions, the steady-state penetration of APFO from a 20% solution was approximately 34-fold faster through rat skin than human skin. [ABSTRACT FROM AUTHOR]

Dodecanediamine (DDDA) is used in the production of specialty polymers. Exposure to this chemical was associated with dermal sensitization in pilot-plant workers, and the possibility that the chemical could produce dermal sensitization was confirmed in a guinea pig test. This property and its dermal irritative properties demonstrate the need to limit skin contact. The possibility of exposure via inhalation also exists. Although stable under ambient conditions, DDDA is processed at elevated temperatures where it may fume, forming a carbamate after reaction with atmospheric carbon dioxide. Some of the carbamate may be converted back to the diamine after hydrolysis in tissue. The rat was used to evaluate the effects of both acute and repeated exposure following inhalation. Fumed DDDA was found to be moderately toxic following a single 4-h exposure with lethality seen at concentrations of 680 mg/m3 or higher. Rats were then exposed to concentrations of either 0 (control), 11, 34, or 98 mg fumed DDDA/m3, 6 h/day, 5 days/wk for 2 wk. Mortality was seen at the highest concentrations, along with increased lung weights. In these rats, laryngeal and tracheal lesions consisting of acute necrosis and inflammation were seen, but surviving rats given a 14-day recovery period showed almost complete recovery. Tracheal and laryngeal lesions were not seen in rats exposed to either 11 or 34 mg/m3. Degenerative and necrotizing lesions were seen in the nasal regions, primarily the respiratory mucosa, of rats in all three treatment groups. The lesions were exposure related with regard to incidence and severity, but regeneration was seen following the recovery period. No evidence of systemic toxicity was seen. The dose-response characteristics of the nasal lesions and the sensitization potential suggest that workplace control levels of 0.1 mg/m3 should be sufficient to protect workers against the untoward effects of fumed DDDA. [ABSTRACT FROM AUTHOR]

The potential maternal and developmental toxicity of cyclododecatriene (CDDT) was assessed in rats. Groups of 22 time-mated female Crl:CD® (SD) BR rats were exposed by inhalation (whole-body, 6 h/day) to either 0 (control), 10, 25, or 67 ppm CDDT over days 6-20 of gestation (days 6-20 G); the day of copulation plug detection was designated day 0 G. The dams were euthanized on day 21 G, and their abdominal and thoracic viscera were examined grossly. The fetuses were weighed, sexed, and examined for external, visceral, and skeletal alterations. Evidence of maternal toxicity was seen at 25 and 67 ppm. There were compound-related reductions in maternal body weight and food consumption parameters as well as increased occurrences of wet and stained fur at these exposure levels. Developmental toxicity evident as reduced mean fetal weight and delayed skeletal ossification was seen only at 67 ppm. There was no evidence of either maternal or developmental toxicity at 10 ppm. Thus, the no-observed-effect level (NOEL) for maternal toxicity was 10 ppm, and the NOEL for developmental toxicity was 25 ppm. Because developmental toxicity was observed only after exposures that also produced signs of maternal toxicity, CDDT was not considered to be a selective developmental toxicant in the rat. [ABSTRACT FROM AUTHOR]

Methylglutaronitrile (MGN) is a high-boiling (263°C) solvent/intermediate used in the fiber industry. Twenty male rats per group were exposed nose-only to condensation aerosol/vapor concentrations of approximately either 5, 25, or 200 mg/m[SUP3] of MGN for 6 h/day, 5 days/week over a 4-week period. Ten rats/group were sacrificed one day after the final exposure and the remaining rats after a four-week recovery period. No effects were observed in clinical observations during the exposure period, but body-weight depression was observed in the 200 mg/m[SUP3] group. The 200 mg/m[SUP3] group showed minimal decreases in red blood cell count, hemoglobin, and hematocrit values accompanied by increases in reticulocytes. There were no other effects observed in clinical or pathologic evaluations in the study. A neurobehavioral battery of tests (including grip strength, functional observational battery, and motor activity tests) given at the end of the exposure and recovery periods showed no MGN effects. During the 4-week recovery, body weights in the 200 mg/m[SUP3]group returned to normal and the hematologic findings in all groups were normal. Based on the above findings of body weight depression at 200 mg/m[SUP3], the no-observed-adverse-effect level (NOAEL) for this study was considered to be 25 mg/m[SUP3]. [ABSTRACT FROM AUTHOR]

Rats were exposed by inhalation to either 0.5 ppm 1,4-dichlorobutene-2 (DCB) for two years or to 5.0 ppm for seven months, 2.5 ppm for five months, and no further exposure for 12 months prior to sacrifice. Malignant and non-malignant tumors of the nasal tissues were seen in both test groups with the incidence and proportion of malignant tumors being much higher in the 5.0/2.5 ppm rats. Under the conditions of this study, DCB is carcinogenic in rats of both sexes. [ABSTRACT FROM AUTHOR]

Groups of 20 male Crl:CDBR rats each were exposed, whole-body, for six hours/day, for a total of nine exposures over a two-week period to concentrations of 52, 150, or 500ppm of 1,5-cyclooctadiene vapor. A control group of 20 male rats was exposed simultaneously to houseline air. Ten rats per group were used for standard toxicological evaluations and ten rats per group for neurotoxicity testing. In the standard toxicology group, at the end of the exposure period, blood and urine samples were collected for clinical analyses, and five rats per group were sacrificed for pathologic examination. After a two-week recovery period, the surviving rats in the standard groups were also given clinical and pathological examinations. The neurotoxicity group was given a functional observational battery (FOB) test and motor activity evaluations after the fourth and ninth exposures. In addition, six of ten neurotoxicity rats per exposure group were given neuropathology evaluations at the end of the exposure period. In rats exposed to 500ppm of 1,5-cyclooctadiene there was an absence of alerting response toward the end of the daily six-hour exposures. These rats appeared to recover within 1/2 hour after exposure. This effect was not observed in the other test groups. The FOB evaluation showed an increase in the number of rats found sleeping in the 500 and 150ppm groups compared to controls after the last exposure, but there were no treatment-related effects in the motor activity evaluation. Since there were no other neurobehavioral findings and no toxicity findings in the 150ppm group, the sleeping behavior in the 150ppm group was considered insufficient evidence of an adverse effect. Clinical laboratory evaluation of the 500ppm group showed urinary pH decreases at the end of the exposure period but not after the twoweek recovery period. There were no other toxicologically important changes in urine analysis, hematologic, or blood chemistry evaluations... [ABSTRACT FROM AUTHOR]

The primary goal of this study is to determine the effects of Mn exposure via inhalation. The bioaccumulation of Mn in different organs and tissues, the alteration of biochemical parameters, and the locomotor activity were assessed. A group of 26 male Sprague-Dawley rats (E) were exposed to 3750 µg/m[sup 3] of Mn dust for 6 h/day, 5 days/wk for 13 consecutive weeks and compared to a control group of 12 rats (C) exposed to 4 µg/m[sup 3]. After exposure, neurological evaluation was carried out for 36 h (a night-day-night cycle) using a computerized autotrack system. Rats were then sacrificed by exsanguination, and Mn content in organs and tissues was determined by neutron activation analysis. Mn concentrations in lung, putamen, and cerebellum were significantly higher in E than in C (0.30 vs. 0.17, 0.89 vs. 0.44, 0.63 vs. 0.48 ppm; p < .01), as well as in the kidney, frontal cortex, and globus pallidus (1.15 vs. 0.96, 0.84 vs. 0.47, 1.28 vs. 0.55 ppm; p < .05). Potassium concentration was significantly lower in E than in C (5.11 vs. 5.79 mmol/L; p < .05), as was alkaline phosphatase (106.9 vs. 129.6 U/L; p < .01). Locomotor activity indicated higher distance covered in the first 12-h period for E (45 383 vs. 36 098 cm; p < .05) and lower resting time in the last 12-h period for E (36 326 vs. 37 393 s; p < .05). This study is the first of several ongoing studies in our laboratory that address health concerns associated with inhalation exposure to different Mn species and to different levels of exposure. [ABSTRACT FROM AUTHOR]

Pentane (CAS No. 109-66-0) is a chemical being used as a co-solvent in a polymer production facility with potential for inhalation exposure in humans. To assess the toxicity of pentane, groups of 10 male rats each were exposed by inhalation, 6 hr/day, 5 days/week for 2 weeks to either 0 (control), 1,000, 3,000 or 10,000ppm. Five rats per group were killed following the 10th exposure; the remaining 5/group were killed after a 14-day post-exposure recovery period. Parameters investigated were clinical signs of toxicity, functional behavior, body weights, clinical pathology, and gross and microscopic pathology including organ weights. No unusual clinical observations were seen in the pentane-treated rats, and body weights were not altered. Test rats generally exhibited normal behavioral responses in the functional observational battery. Increases in serum calcium and phosphorus concentrations were seen in rats exposed to either 3,000 or 10,000 ppm. These were reversible during the 2-week recovery period. No other clinical pathology changes were observed and no pentane-related tissue pathology was seen in any of the groups. The no-observed-adverse-effect level was 1,000 ppm with reversible clinical pathology changes produced at 3,000 and 10,000 ppm. [ABSTRACT FROM AUTHOR]

The potential developmental toxicity of 3-aminopentanenitrile (3-APN) was assessed in rats. Groups of 25 time-mated female Crl:CD®(SD)IGS BR rats were orally gavaged at daily dose levels of 0, 5, 30, 100 or 300 mg/kg over days 6-20 of gestation (days 6-20G); the day of copulation plug detection was designated day 0G. The dams were euthanized on day 21G and their abdominal and thoracic viscera were examined grossly. The fetuses were weighed, sexed, and examined for external, visceral, and skeletal alterations. Evidence of maternal and developmental toxicity was seen at 100 and 300 mg/kg. Regarding maternal toxicity, there were compound-related, statistically significant reductions in maternal body weight and food consumption at 100 and 300 mg/kg. The incidence of alopecia was significantly increased at these levels as well. Regarding developmental toxicity, mean fetal weight was slightly but significantly reduced at 100 and 300mg/kg. In addition, at 300mg/kg, there were significant increases in several skeletal variations (wavy ribs and skull, rib, and vertebral ossification delays) consistent with developmental delay. There was no evidence of either maternal or developmental toxicity at 5 or 30mg/kg. Thus, the maternal and developmental no-observed-effect level (NOEL) was 30mg/kg. Because developmental toxicity was observed only after administration of doses that also produced signs of maternal toxicity, 3-APN is not considered to be a selective developmental toxicant in the rat. [ABSTRACT FROM AUTHOR]

Four chemicals (Dioxole 418, Dioxolane 418, Dioxolane 416 and Dioxolane 456) which are used as stabilizers in highresolution image were tested or both their acute and repeated inhalation toxicity in the rat using nose-only exposures. Acute studies determined the lethal concentrations following a single 4-hour exposure; repeated exposure inhalation studies determined the potency and target tissue(s) following 6-hour/ day exposures, 5 days/week for 2 weeks. Each of the chemicals was at least mildly toxic acutely with approximate lethal concentrations of > 1,500 ppm for Dioxole 418, 1,300 ppm for Dioxolane 418, 1,700 ppm for Dioxolane 416, and 4,300 ppm for Dioxolane 456. No specific unusual clinical signs of response were seen in the rats exposed acutely. Repeated exposures with Dioxole 418 and Dioxolane 418 resulted in no evidence of toxicity with NOAEL's being 440 and 500 ppm respectively (the highest concentrations tested). Repeated exposures to 250 ppm Dioxolane 456 were not tolerated with mortalities observed after exposure. Severe bone marrow hypoplasia along with reductions in platelet and neutrophil counts were observed at this concentration with less severe hemopoietic changes seen also at 10 and 51 ppm. The no-effect level for Dioxolane 456 was determined to be 10 ppm in female rats and I ppm in males. The same hemopoietic effects were seen with Dioxolane 416 at exposures of 53 ppm or greater in males but not in females exposed to 53 ppm Dioxolane 416. Hepatocellular hypertrophy and depression of serum alkaline phosphatase activity were seen in male rats exposed to 500 but not 53 ppm Dioxolane 416. Testicular degeneration was also seen in rats exposed to 500 ppm Dioxolane 416. The NOAEL was 5 ppm for the chemical. [ABSTRACT FROM AUTHOR]

Welder exposure to metals in various industrial sectors is poorly characterized. We had the opportunity to carry out an exploratory study to characterize manganese exposure in welding operations in a recently established Quebec factory that assembled accessories for heavy excavation machinery. Ten workers were sampled for total manganese for at least two consecutive days out of three followed by two consecutive days for respirable manganese (with a size selective sampler with a median cut-off of 4 μm), during a typical week in the summer of 1998. Parts being welded were characterized as large or small. Small parts were those being welded on tables during subassembly. Workers were divided into two groups according to the parts they were welding. Seventy-eight percent of the total manganese exposure levels of welding operations during the assembly of large accessories of heavy excavation machinery exceeded the manganese American Conference of Governmental Industrial Hygienists (ACGIH [sup ®]) threshold limit value (TLV [sup ®]) of 0.20 mg/m³ (GM 0.24 mg/m³, n = 14) while none exceeded the TLV during the assembly of small pieces (GM 0.06 mg/m³, n = 8). Welding operations during the assembly of large heavy excavation machinery accessories may pose a significant health hazard. Considering the importance of task-related variables affecting exposure among workers, further studies are needed to better characterize exposure determinants of welding operations during the assembly of heavy excavation machinery accessories. [ABSTRACT FROM AUTHOR]

This study was conducted to elucidate the time- and dose-response relationships of long-term, low-level 1,4-dichlorobutene-2 (DCB) inhalation exposure to nasal tumor induction in rats. Male Crl:CD®BR rats were exposed 6 hours per day, 5 days week to 0, 0.1, 0.3, or 1.0 ppm DCB for up to 19 months; some rats were sacrificed at various time intervals during the study. After 19 months of exposure, surviving rats were held without treatment for an additional 5 months. Tissues from the respiratory tract, lymph nodes, and brain were evaluated microscopically. Compound-related non-neoplastic lesions were observed in the nasal cavities of rats in the 1.0 ppm group after three months of exposure and in the other two groups after twelve months of exposure. The lesions were progressive in severity and frequency. A statistically significant increase in benign nasal tumors (adenomas) occurred in rats from all three DCB-exposed groups. The adenomas occurred in the respiratory region of the nasal cavity and were first observed in the 1.0 ppm group at study month 10. Malignant nasal tumors occurred in the olfactory region of the nasal cavity and were statistically increased at 1.0 ppm. [ABSTRACT FROM AUTHOR]

Abstract: Deficiencies of antioxidant nutrients have been implicated in the etiology of lung and other cancers. However, most intervention trials with antioxidant nutrients have not shown beneficial effects, and some have indicated that beta-carotene may be deleterious. This randomized, doubleblind, placebo-controlled study evaluated the effects of five short-term (4-wk) antioxidant nutrient supplement regimens [ascorbic acid (350 mg), RRR-alpha-tocopherol (250 mg), betacarotene (60 mg), selenium (80 mug as sodium selenite), ascorbic acid (350 mg) + RRR-alpha-tocopherol (250 mg)] on plasma antioxidants and mononuclear leukocyte DNA damage in male smokers (n = 9) and nonsmokers (n = 12). Plasma concentrations of ascorbic acid and tocopherol were significantly increased by supplementation, but there was no significant change in plasma beta-carotene or blood glutathione peroxidase activity after supplementation with betacarotene or selenium. DNA damage in mononuclear leukocytes, as assessed by comet assay, was not affected by any supplementation regimen. DNA damage, as assessed by 8-hydroxydeoxyguanosine in mononuclear leukocytes, was not influenced by ascorbic acid, alpha-tocopherol, or selenium supplementation in smokers or nonsmokers, but beta-carotene supplementation resulted in significant differences between smokers and nonsmokers in the level of oxidative DNA damage, with decreases in smokers and increases in smokers. This is a further indication of the differential effects of supplemental beta-carotene in smokers and nonsmokers. [ABSTRACT FROM AUTHOR]

A foreword to this issue of the journal is presented.

A letter to the editor is presented on the effects of post-therapy calcification in false-positive fluorodeoxyglucose positron emission tomography scans in patients with non-Hodgkin's lymphoma.

A two-year feeding study in rats and an 18-month feeding study in mice were conducted to evaluate the potential chronic toxicity and oncogenicity of NMP in Crl:CD® (SD)BR rats and B6C3F1/CrlBR mice. Groups of 62 male and female rats were administered diets containing 0, 1600, 5000, or 15000ppm of NMP for approximately 2 years. Groups of 50 male and female mice were administered diets containing 0, 600, 1200, or 7200ppm NMP for approximately 18 months. In vivo parameters were evaluated weekly during the first 3 months of the study, and every other week or monthly during the remainder of the study. For rats, an ophthalmoscopic examination was conducted prior to study start and near the end of the study. Periodically, blood samples were collected from rats and mice for determination of leukocyte differential counts, and from mice for red blood cell morphology. After approximately 2 years of dietary administration in rats and 18 months in mice, all surviving animals were sacrificed. Selected tissues were processed for morphological evaluation. Over the course of the two-year study in rats, test substance-related decrements in body weight and weight gain occurred in 15000ppm males and females, which correlated with decreased food consumption and food efficiency. A toxicologically significant, test substance-related increase in the incidence of severe chronic progressive nephropathy occurred in 15000ppm males. Several morphological changes noted grossly and/or microscopically were secondary to the increased severity of chronic progressive nephropathy. NMP was not oncogenic in male or female rats at dietary concentrations of 15000ppm and below. A test substance-related decrease in the percentage of 15000ppm males surviving to the end of the two-year study compared to the control group resulted from the higher incidence of severe chronic progressive nephropathy. However, a sufficient population of 15 000 ppm rats were at risk for potential oncogenicity, so the... [ABSTRACT FROM AUTHOR]

Tetramethylurea (TMU, CAS No. 632-22-4) was tested for its inhalation toxicity in rats following repeated exposures. Male rats were exposed whole-body to TMU for 6 hours/day, 5 days/week for a total of 9 exposures over 2 weeks. Concentrations of 0 (control), 2, 20, and 100ppm were studied. Four groups of 10 rats each were used to measure clinical signs and growth, clinical pathology (including hematology, biochemistries, and urine analysis), and tissue pathology. One-half of the rats were sacrificed 1 day following the 9th exposure; the other half underwent an 18-day recovery period prior to being sacrificed (recovery group). Body weight gains in rats exposed to 100 ppm were reduced as compared to the controls; no body weight effects were seen in either 2 or 20 ppm rats and no clinical signs of toxicity were observed in rats at any of the levels throughout the study. No compound-related clinical pathology changes were seen in any of the test groups and tissue pathology effects only occurred in the nasal tissue. In rats exposed to 100ppm, microscopic observations of degeneration, necrosis, and ulceration of olfactory mucosa was seen. These lesions were still present but seen as recovering and healing after the 18-day recovery. Under the conditions of this test, the no-observed-adverse-effect level (NOAEL) was determined to be 20ppm based upon both body weight changes and upper respiratory tract pathologic changes in 100 ppm rats. [ABSTRACT FROM AUTHOR]

The developmental toxicity of glycolic acid was assessed in rats by orally administering solutions of the test material in water over days 7-21 of gestation (the day of copulation plug detection was definedas day 1 of gestation). Groups of 25 mated female Crl:CD(R)BR rats were gavaged at daily dose levels of 0, 75, 150, 300 or 600mg/kg. The dams were euthanized on day 22 and the offspring were weighed, sexed, and examined for external, visceral, and skeletal alterations. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg; adverse clinical observations were statistically significantly increased (wheezing/lung noise, abnormal gait/staggering, lethargy). In addition, maternal body weights, weight changes, and food consumption were statistically significantly reduced at this dose level. Marginal evidence of maternal toxicity was demonstrated at 300 mg/kg; wheezing/lung noise similar to that seen at 600 mg/kg was observed in 2 of 25 dams. This increase approached statistical significance (p=0.0553). There was marked evidence of developmental toxicity at 600 mg/kg.Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. At 300 mg/kg/day, there was a slight (2 affected fetuses from 2 litters) increase in the incidence of two skeletal malformations: fused ribs and fused vertebra. Although these increases were not statistically significant (p=0.0555), they were consistent with findings seen at 600 mg/kg/day and thus were considered relevant. There was no other evidence ofdevelopmental toxicity at 300 mg/kg/day nor was any developmental toxicity seen at 150 or 75 mg/kg/day. Thus, the maternal and developmental no-observed-effect level (NOEL) was considered 150 mg/kg. [ABSTRACT FROM AUTHOR]

Ninety-day feeding studies were conducted to evaluate the repeated dose toxicity of NMP, a widely used industrial solvent, in Crl:CD(R)BR rats and B6C3F1 mice. Groups of 20 to 26 male and female rats each were fed either 0, 3,000, 7,500, or 18,000 ppm NMP for 90 days. Groups of 10 male and female mice were fed either 0, 1,000, 2,500, or 7,500 ppm NMP for 28 or 90 days. In vivo parameters, hematologyand clinical chemistry parameters, ophthalmologic examinations, functional and histopathologic neurologic parameters (rats only), and complete pathology evaluations were conducted after 90 days. Decreases in mean body weights, reflecting decreases in food consumption and efficiency were observed in male and female rats fed either 7,500 or 18,000 ppm NMP. A change in urine coloration was observed at 3,000 ppm and above in both males and females. This was considered to be evidence of systemic availability since it was not associated with any functional or pathological changes. Of 36 neurobehavioral parameters investigated, male rats in the 7,500 and 18,000 ppm groups showed an increase in foot splay, and 18,000 ppm males had a higher incidence of lowarousal and slight palpebral closure suggestive of a sedative effect. Absolute and relative liver weights were increased in 18,000 ppm females which were associated with an increased incidence of centrilobular hepatocellular hypertrophy and were considered to be an adaptive/physiological response. Absolute and relative kidney weights were increased in 18,000 ppm males and females, however, there were no pathological or functional changes associated with the increases. In mice, there were no effects on body weight or food consumption. As observedin rats, mice fed 2,500 or 7,500 ppm exhibited a change in urine coloration which was not associated with morphological changes in the kidney. In 2,500 and/or 7,500 ppm mice, changes in cholesterol, triglycerides, calcium, and alkaline phosphatase occurred at 28 days but not90 [ABSTRACT FROM AUTHOR]

Twenty-eight day feeding studies were conducted to evaluate the repeated dose toxicity of NMP, a widely used industrial solvent, in Crl:CD(R)BR rats and B6C3F1 mice. Groups of 5 male and 5 female rats each were fed either 0, 2,000, 6,000, 18,000, or 30,000 ppm NMP; similar groups of mice were fed either 0, 500, 2,500, 7,500, or 10,000 ppm. Invivo parameters, hematology and clinical chemistry parameters, and complete pathology evaluations were conducted after approximately 28 days. Decrements in mean body weight gains, reflecting decreases in food consumption and efficiency, were seen in male rats fed 18,000 ppm and in both sexes fed 30,000 ppm. In rats, clinical chemical changes,indicating possible compound-related alterations in lipid, protein, and carbohydrate metabolism, occurred at 18,000 ppm in males and 30,000 ppm in both sexes. No histopathological changes in rats were judged to be directly related to NMP exposure. Hematological (mild to moderate leukopenia) and histopathological alterations (hypocellular bonemarrow, testicular degeneration and atrophy, and thymic atrophy) were judged to be secondary to nutritional and body weight effects in male and/or female rats at 30,000 ppm. In mice, cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10,000 ppm and in 2 male mice at 7,500 ppm. Forboth rats and mice, abnormal urine coloration was observed (in mice at 2,500 ppm and above, and in rats at 18,000 ppm and above). This discoloration was interpreted as a sign of systemic availability of thetest substance, but not as an adverse effect. The NOAEL was 6,000 ppm for mate rats and 18,000 ppm for female rats. In mice, the NOAEL was 2,500 ppm based on the kidney histopathology. [ABSTRACT FROM AUTHOR]