Subchronic toxicity evaluation of potato protein isolates.

The protein content of potatoes has a high nutritional value on par with eggs and soybeans. As a result, processed potato protein isolates may have commercial value for addition to other food products to increase protein content. A manufacturing process has been developed to produce total potato (TP), as well as low (LMW) and high molecular (HMW) weight, protein isolates as food ingredients. To assess the safety of these isolates, groups of 10 Wistar rats/sex were administered dietary admixtures containing 15% HMW, 7.5% LMW or 15% TP protein isolates for a period of 90days. There was no effect of treatment on clinical signs, mortality, body weight and body weight gain. No biologically significant changes occurred in hematological and clinical chemistry parameters. No statistically significant changes in organ weights were recorded. Histopathological analyses revealed no clear, treatment-related changes. A slight increase in the incidence, but not severity, of vacuolation of the zona fasciculate of the adrenal gland was noted in males of the 15% HMW and 7.5% LMW groups. The finding was not considered adverse or ascribed any toxicological significance. Overall, HMW, LMW, and TP protein isolates were well-tolerated and without adverse effect. These data support the safety of potato protein isolates.

Neurobehavioral effects of cyclohexane in rat and human.

The neurobehavioral effects of inhaled cyclohexane in rats and humans are investigated to define relationships between internal doses and acute central nervous system effects. Rats are exposed for 3 consecutive days at target concentrations of 0, 1.4, 8, and 28 g/m(3), 8 h/d. Measurements include standardized observational measures, spontaneous motor activity assessments, and learned visual discrimination performance. Cyclohexane concentrations in blood and brain are measured to assess internal exposure. Human volunteers are exposed for 4 hours to 86 or 860 mg/m(3) in 2 test sessions. Neurobehavioral effects are measured using a computerized neurobehavioral test battery. In rats, there are slight reductions in psychomotor speed in the high-exposure group but minimal central nervous system effects. In humans, there are no significant treatment-related effects at the levels tested.

Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents II. Neurobehavioral effects of white spirit in rat and human.

To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate the behavioral effects of exposure to WS in rats and humans and to determine relationships between internal levels of exposure and behavioral effects. In both animals and volunteers, methods for assessment of similar functional effects were used to enable interspecies comparisons. A battery of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute central nervous system (CNS) depression. Groups of rats were exposed to WS at target concentrations of 0, 600, 2400 or 4800mg/m(3), 8h/day for 3 consecutive days. Blood and brain concentrations of two WS constituents; 1,2,4-trimethylbenzene (TMB) and n-decane (NDEC), were used as biomarkers of internal exposure. In a volunteer study, 12 healthy male subjects were exposed for 4h to either 57 or 570mg/m(3) WS in two test sessions spaced 7 days apart, and neurobehavioral effects were measured using a computerized neurobehavioral test battery. Blood samples were taken at the end of the exposure period to measure internal concentrations of TMB and NDEC. Results of the behavioral tests in rats indicated WS-induced changes particularly in performance and learned behavior. In humans, some subtle performance deficits were observed, particularly in attention. The behavioral effects were related to concentrations of the WS components in the central nervous system. These studies demonstrated a qualitative similarity in response between rats and humans, adding support to the view that the rodent tests can be used to predict levels of response in humans and to assist in setting occupational exposure levels for hydrocarbon solvents.

Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol.

As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to evaluate the acute central nervous system (CNS) effects of ethanol in rats and humans and to assess relationships between internal levels of exposure and behavioral effects. A more general objective was to validate a battery of neurobehavioral tests that could be used to carry out comparative studies in both species. Accordingly, a range of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute CNS effects. Groups of rats were given ethanol at levels of approximately 0.5, 1.0 or 2.0g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3h after ethanol administration, with a computerized neurobehavioral test battery. Blood and air measurements were made to quantify internal doses. Results of the behavioral tests in rats provided evidence of ethanol-induced changes in neuromuscular, sensori-motor, and activity domains. There were also significant changes in visual discrimination, particularly in the areas of general measures of responding and psychomotor speed. In humans there were small but statistically significant effects on learning and memory, psychomotor skills and attention. However, the effects were subtle and not all parameters within given domains were affected. These studies demonstrated a qualitative similarity in response between rats and humans.

Human volunteer study with PGME: eye irritation during vapour exposure.

The objective of this study was to establish the possible occurrence of eye irritation and subjective symptoms in human volunteers exposed to propylene glycol monomethyl ether (PGME) vapour at concentrations of 0, 100 and 150 ppm. Testing was conducted in 12 healthy male volunteers using a repeated measures design. Each subject was exposed for 2.5 h to each of the three exposure conditions that were spaced 7 days apart. The exposure sequences were counterbalanced and the exposure to the test substance and the effect measurements were conducted in a double-blind fashion. During all exposure sessions, 20 ppm diethyl ether was used as a 'masking agent' for vapour exposure. Measurements of pre- and post exposure eye redness, corneal thickness, tear film break-up time, conjunctival epithelial damage, blinking frequency, and subjective ratings on discomfort were used to evaluate the possible irritating effects of PGME. The results indicated no significant treatment effects for any of the objective parameters. Results of the subjective ratings indicated very slight effects on the eyes in the 150 ppm PGME condition only. No significant effects of treatment were found for the remaining questions concerning the perceived intensity of the smell in the room, the (un)pleasantness of the smell, the perceived effects on the skin, effects on the throat, shivering, muscle aching, and intestinal cramps. In conclusion, the results of the present study indicated minimal subjective eye effects at 150 ppm only, and no impact on the objective measures of eye irritation at either of the two exposure levels. It was concluded that the no adverse effect concentration for eye irritation due to PGME vapour was at least 150 ppm.

An analysis of human response to the irritancy of acetone vapors.

Studies on the irritative effects of acetone vapor in humans and experimental animals have revealed large differences in the lowest acetone concentration found to be irritative to the respiratory tract and eyes. This has brought on much confusion in the process of setting occupational exposure limits for acetone. A literature survey was carried out focusing on the differences in results between studies using subjective (neuro)behavioral methods (questionnaires) and studies using objective measurements to detect odor and irritation thresholds. A critical review of published studies revealed that the odor detection threshold of acetone ranges from about 20 to about 400 ppm. Loss of sensitivity due to adaptation and/or habituation to acetone odor may occur, as was shown in studies comparing workers previously exposed to acetone with previously unexposed subjects. It further appeared that the sensory irritation threshold of acetone lies between 10,000 and 40,000 ppm. Thus, the threshold for sensory irritation is much higher than the odor detection limit, a conclusion that is supported by observations in anosmics, showing a ten times higher irritation threshold level than the odor threshold found in normosmics. The two-times higher sensory irritation threshold observed in acetone-exposed workers compared with previously nonexposed controls can apart from adaptation be ascribed to habituation. An evaluation of studies on subjectively reported irritation at acetone concentrations < 1000 ppm shows that perception of odor intensity, information bias, and exposure history (i.e., habituation) are confounding factors in the reporting of irritation thresholds and health symptoms. In conclusion, subjective measures alone are inappropriate for establishing sensory irritation effects and sensory irritation threshold levels of odorants such as acetone. Clearly, the sensory irritation threshold of acetone should be based on objective measurements.

Human safety and pharmacokinetics of the CFC alternative propellants HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) following whole-body exposure.

HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) are used to replace chlorofluorocarbons (CFCs) in refrigerant and aerosol applications, including medical use in metered-dose inhalers. Production and consumption of CFCs are being phased out under the Montreal Protocol on Substances that Deplete the Ozone Layer. The safety and pharmacokinetics of HFC 134a and HFC 227 were assessed in two separate double-blind studies. Each HFC (hydrofluorocarbon) was administered via whole-body exposure as a vapor to eight (four male and four female) healthy volunteers. Volunteers were exposed, once weekly for 1 h, first to air and then to ascending concentrations of HFC (1000, 2000, 4000, and 8000 parts per million (ppm)), interspersed with a second air exposure and two CFC 12 (dichlorodifluoromethane) exposures (1000 and 4000 ppm). Comparison of either HFC 134a or HFC 227 to CFC 12 or air gave no clinically significant results for any of the measured laboratory parameters. There were no notable adverse events, there was no evidence of effects on the central nervous system, and there were no symptoms of upper respiratory tract irritation. HFC 134a, HFC 227, and CFC 12 blood concentrations increased rapidly and in an exposure-concentration-dependent manner, although not strictly proportionally, and approached steady state. Maximum blood concentrations (C(max)) tended to be higher in males than females; in the HFC 227 study, these were statistically significantly (P < 0. 05) higher in males for each HFC 227 and CFC 12 exposure level. In the HFC 134a study, the gender difference in C(max) was only statistically significant (P < 0.05) for CFC 12 at 4000 ppm and HFC 134a at 8000 ppm. Following the end of exposure, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration. For the HFC 134a study, the t(1/2)alpha (alpha elimination half-life) was short for both CFC 12 and HFC 134a (<11 min). The t(1/2)beta (beta elimination half-life) across all exposure concentrations was a mean of 36 and 42 min for CFC 12 and HFC 134a, respectively. Mean residence time (MRT) was an overall mean of 42 and 44 min for CFC 12 and HFC 134a, respectively. In the HFC 227 study, t(1/2)alpha for both CFC 12 and HFC 227, at each exposure level, was short (<9 min) and tended to be lower in males than females. For CFC 12 mean t(1/2)beta ranged from 23 to 43 min and for HFC 227 the mean range was 19-92 min. The values tended to be lower for females than males for HFC 227. For both CFC 12 and HFC 227, MRT was statistically significantly lower (P < 0.05) in males than females and independent of exposure concentration. For CFC 12, MRT was a mean of 37 and 45 min for males and females, respectively, and for HFC 227 MRT was a mean of 36 and 42 min, respectively. Exposure of healthy volunteers to exposure levels up to 8000 ppm HFC 134a, 8000 ppm HFC 227, and 4000 ppm CFC 12 did not result in any adverse effects on pulse, blood pressure, electrocardiogram, or lung function.

Behavioral effects of exposure to organic solvents in carpet layers.

Carpet layers and age-matched controls were investigated both at the beginning of a working day and at the end with four subtests of a neuropsychological test battery (NES2). Exposure to toluene, cyclohexane, ethyl acetate, and heptane was measured with personal air sampling methods. One group of carpet layers used water-based adhesives (WBA) on the day the investigation took place and the other group used contact adhesives (CA) on that day. The WBA group was exposed primarily to toluene, and the CA group was exposed to other solvents as well. Initial (before work) differences in neuropsychological scores between all exposed workers and controls could be attributed to differences in education, the carpet layers being somewhat higher educated. No differences were found between the solvent-exposed and control groups that would suggest persistent effects of chronic solvent exposures. The improvement in test scores over the day was the same in both groups. However, evidence for exposure-related changes in test scores over the day were found within the exposed group.

Symptoms indicative of the effects of organic solvent exposure in Dutch painters.

The report describes the results of a cross-sectional study among two groups of young and older painters and two age-matched control groups. The study was intended to gather information on the occurrence of solvent-exposure symptoms among Dutch workers using a mailed questionnaire. Results indicated that among young painters and to a lesser extent among older painters what is commonly accepted as specific symptoms and additional solvent-related symptoms showed a higher frequency than among the controls. The most interesting observation was a significant relationship between the frequency of periods of heavy exposure and the severity of most symptom categories, whereas there was a lack of consistent relationships with other exposure parameters.

The effects of 4-aminopyridine on cognitive function in patients with multiple sclerosis: a pilot study.

4-Aminopyridine (4-AP) has a favorable effect on the disability of certain patients with MS. We investigated the effect of 4-AP on neuropsychological performance in 20 MS patients using a randomized, double-blind, placebo-controlled, crossover design. Although there was a trend for improved performance with 4-AP for two of the tests, we could not demonstrate significant effects of 4-AP on cognitive function.

Neurobehavioral effects of long-term exposure to xylene and mixed organic solvents in shipyard spray painters.

A cross-sectional study was performed in shipyard painters exposed to organic solvents and age-matched referents. The work duties of the painters mainly involved spray painting with solvent-based paints containing > 50% xylene. Testing methods consisted of a symptoms questionnaire, measurement of peripheral sensory and motor nerve parameters and computerized performance tests. Results indicate that complaints regarding mood changes, equilibrium and fatigue were more severe in painters than in referents, but were not related to the estimated life-time exposure index. Decreased nerve function was observed in the lower extremities and to some extent in the upper extremities. The refractory period appeared to be a sensitive parameter in motor nerves. Most neurophysiological parameters investigated were significantly related to the exposure index. Behavioral testing revealed impairment of simple visuo-motor performance and complex perceptual coding. A relationship between effects on perceptual coding and the exposure index was also demonstrated.

Behavioral effects of exposure to organic solvents in Dutch painters.

The report describes the results of a cross-sectional study of solvent-exposed young and older Dutch painters and two age-matched control groups. Both traditional and computerized neurobehavioral tests were applied. The study did not detect any major differences between the two groups of painters and their two age-matched control groups. It is argued that this absence of differences is probably not due to a lack of sensitivity of the tests applied or the size of the groups studied. The level of exposure was estimated to be within a range at which previous authors have reported solvent-induced CNS effects.

Encephalopathy in patients on continuous ambulatory peritoneal dialysis and patients on chronic haemodialysis.

A group of 121 patients, 22 with a preterminal chronic renal insufficiency (PCRI), 74 on chronic haemodialysis (CHD), and 25 on continuous ambulatory peritoneal dialysis (CAPD), was evaluated by means of neurophysiological and neuropsychological studies to detect signs of central nervous system dysfunction. CHD patients were studied the day before dialysis treatment. In each patient the neurophysiological and neuropsychological studies were performed on the same day. The same overall result emerged from the neurophysiological and neuropsychological studies: all three patient groups showed significant deviations from the values obtained from a healthy reference group, whereas no differences were found between the three patient groups. Biochemical variables (a.o. PTH, Al, PO4) showed inconsistent or only minor correlations with the encephalopathic parameters. Apparently traditional biochemical variables are not a reliable measure to safeguard renal patients from neurotoxic damage. With respect to central nervous system dysfunction CAPD appears to be as 'safe' as CHD.

Health effects of pesticides in the flower-bulb culture in Holland.

In a comprehensive project the health risk for workers using pesticides in the flower-bulb culture was addressed in several studies regarding biological monitoring, occupational hygiene and health effects. With respect to biological monitoring, methods were developed for the analysis of metabolites in urine of captan, pirimicarb, zineb and maneb and the soil fumigant dichloropropene. For dichloropropene in a field study a clear relationship was found between the external personal exposure and the excretion of two metabolites (mercapturic acids) in urine. The application technique distinctly influenced the extent of exposure. For the other substances preliminary measurements were performed in the urine of exposed workers; for captan and pirimicarb the methods are promising for further studies of the uptake of these substances under working conditions. In an occupational hygiene study, the dermal exposure due to different application techniques used in crop protection and bulb disinfection was investigated. This resulted in method specific exposure values (grams/field area of bulbs) that showed large differences between the techniques. These exposure values in combination with information on the type of techniques used, the treated area and the frequency of application were used to calculate a personal exposure index (grams/working life); this is an estimate of the potential (external) exposure of individual workers. In an effect study 137 workers who applied pesticides for more than 10 years (average 20 years) in at least bulb disinfection and crop protection (the most important area's of exposure for the growers) were compared to 73 controls. Tests for autonomic and peripheral nerve functions including the distribution of conduction velocities and refractory periods, were applied as well as computerized neurobehavioral tests and electro-encephalography. Significant effects were found on peripheral nerve function parameters, on measures of attention and perceptual coding and on the amount of beta-activity in the EEG; the data suggest that for the majority of subjects these effects are small. No effects were found on liver and renal function and no difference in the prevalence of symptoms that might be ascribed to the usage of pesticides. In a number of exposed workers a cutaneous allergy to pesticides was found. Based on this study, measures are recommended to diminish effectively the exposure to pesticides in this culture.

Relaxation training in school classes does not reduce headache complaints.

The effect of teacher-presented Progressive Relaxation Training (PRT) on headaches, fear of failure and school problems was studied in school students. During ten physical education lessons, students received either PRT (n = 110) or placebo training (n = 92). The effect of the training was investigated in students who indicated the presence of headaches in a pre-training diary. No significant differences were found between both training groups regarding headache frequency, duration and intensity and the psychological variables. On the basis of these and previous findings, it is recommended to present PRT to fairly small groups of self-selected subjects instead of complete classes.

Influence of quality of life and stress coping behaviour on headaches in adolescent male students: an explorative study.

Quality of life (QL) and stress coping behaviour were evaluated in 194 adolescent male students, and related to their headache complaints. Negative correlations were found between headache duration and intensity versus satisfaction with autonomy, and between headache intensity versus satisfaction with the home situation. Both headache duration and intensity were found to correlate positively with depressive stress coping behaviour. Further, positive correlations were found between palliative and avoidant stress coping strategies versus headache intensity. Our findings suggest that active rather than passive stress coping strategies are effective in reducing headache intensity. In addition, this study indicates the relevance of focussing future research into headaches in adolescents on the home situation.

The effect of video-feedback on the learning of the tennis service by intermediate players.

Effects of video-feedback on improvement of the tennis service were investigated in subjects having at least 2 years of playing experience in tennis. The experiment was carried out in an indoor tennis hall under normal training conditions. Subjects were randomly divided into three groups: a video-feedback training (VFT) group, a traditional training (TT) group and a control group, each consisting of 22 subjects. While the subjects of the control group received no training at all, subjects in both the VFT and TT groups were trained twice weekly during 5 consecutive weeks. Each training session lasted 40 min, of which 30 min was spent on actual practice in training of the service. The remaining 10 min was spent on watching, analysing and discussing video recordings of either their own service performed during the training session (VFT group), or ground strokes and volleys of top level players (TT group). Both the VFT and TT group showed significantly greater improvements in both achievement scores and form (technique) scores than did the control group. No differences, however, could be demonstrated between the VFT and TT group, indicating that the subjects of the former group did not benefit from the video-feedback they received. While form scores correlated significantly (P less than 0.001) with the velocity of the served ball, no such relation between form scores and spatial accuracy was apparent.

The effect of video-modelling and video-feedback on the learning of the tennis service by novices.

This project is addressed to the effectiveness of video mediated instruction on the learning of the tennis service by novices. The research was carried out in an indoor tennis hall under normal training conditions. Three experimental groups were used: a video-model (VMT), a video-feedback (VFT) and a group with a combination of video modelling and video feedback (VMFT). Two control groups - based on different training periods-were also used: a traditional training group (TT1) which practised for a period of 45 min per training session and a second traditional training group (TT2) which practised for a period of only 30 min per training session. All subjects took part in five successive training sessions. No clear advantages of using video mediated instruction methods in teaching novices the tennis service could be demonstrated. Five sessions of 30 min practical training were shown to be as effective as five sessions of 45 min practical training in producing improvements in both form and achievement scores of novice tennis players. While, in the early stages, form and achievement scores were not shown to be significantly related, after five sessions a significant correlation (P less than 0.05) was shown.