Quantitative assessment of required separator fluid volume in multi-infusion settings.

BACKGROUND: Administering a separator fluid between incompatible solutions can optimize the use of intravenous lumens. Factors affecting the required separator fluid volume to safely separate incompatible solutions are unknown. METHODS: An intravenous tube (2-m, 2-mL, 6-French) containing methylene blue dye was flushed with separator fluid until a methylene blue concentration ⩽2% from initial was reached. Independent variables were administration rate, dye solvent (glucose 5% and NaCl 0.9%), and separator fluid. In the second part of the study, methylene blue, separator fluid, and eosin yellow were administered in various administration profiles using 2- and 4-mL (2 × 2 m, 4-mL, 6-French) intravenous tubes. RESULTS: Neither administration rate nor solvent affected the separator fluid volume (p = 0.24 and p = 0.12, respectively). Glucose 5% as separator fluid required a marginally smaller mean ± SD separator fluid volume than NaCl 0.9% (3.64 ± 0.13 mL vs 3.82 ± 0.11 mL, p < 0.001). Using 2-mL tubing required less separator fluid volume than 4-mL tubing for methylene blue (3.89 ± 0.57 mL vs 4.91 ± 0.88 mL, p = 0.01) and eosin yellow (4.41 ± 0.56 mL vs 5.63 ± 0.15 mL, p < 0.001). Extended tubing required less separator fluid volume/mL of tubing than smaller tubing for both methylene blue (2 vs 4 mL, 1.54 ± 0.22 vs 1.10 ± 0.19, p < 0.001) and eosin yellow (2 vs 4 mL, 1.75 ± 0.22 vs 1.25 ± 0.03, p < 0.001). CONCLUSION: The separator fluid volume was neither affected by the administration rate nor by solvent. Glucose 5% required a marginally smaller separator fluid volume than NaCl 0.9%, however its clinical impact is debatable. A larger intravenous tubing volume requires a larger separator fluid volume. However, the ratio of separator fluid volume to the tubing's volume decreases as the tubing volume increases.

Derivation of cancer no significant risk levels and screening safety assessment for 2-nitropropane in spray products.

Two proposition 65 no-significant-risk level (NSRL)-type values were derived for 2-nitropropane (2-NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2-NP during indoor application of paint from a spray can containing the solvent 1-nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2-NP single exposure inhalation studies in Sprague-Dawley rats. Several BMD models provided an acceptable fit for the male rat hepatocellular carcinoma incidence data (gamma, log-probit, log-logistic and multistage); therefore, the mean of the BMD lower limits from each model were used as the point of departure to derive the inhalation cancer potency. The oral human cancer potency was derived from the inhalation human cancer potency based on the ratio of the uptake factors for inhalation vs. oral routes. The derived inhalation and oral NSRLs are 67 µg/day and 32 µg/day, respectively. For the inhalation and dermal exposure assessment, three key factors were analyzed: the 2-NP residual concentration in the spray paint product, the mass of spray paint used and the frequency of use. Based on the screening exposure assessment, potential consumer inhalation and dermal exposure to 2-NP from indoor application of paint from a spray can does not exceed our proposed NSRLs, and a warning label is therefore not required for spray can products containing the solvent 1-nitropropane where 2-NP is a minor contaminant.

The health-disease process and the family health strategy: the user's perspective / Processo saúde/doença e estratégia de saúde da família: o olhar do usuário / El proceso salud-enfermedad y la estrategia salud de la familia: la perspectiva del usuario

OBJECTIVE: to analyze the meanings Primary Health Care users attribute to their health-disease process and the services used. METHODS: this qualitative research uses the focus group technique to interview two groups of users the service monitors. The first is a group of elderly people and the second of pregnant women. To analyze the meanings, the discourse analysis technique and the reference framework of health promotion are used. RESULTS: the group of elderly, being mostly female arterial hypertension and diabetes mellitus patients, visualizes the health-disease process as the evolution of human existence controlled by divine power, signifying the health service as a blessing in the control of the disease. The Group of young pregnant women signified health as the ability for self-care and disease as the disability for that purposes, considering the Primary Health Care service as responsible for the recovery of individual and family health. FINAL CONSIDERATIONS: the users demonstrated dissatisfaction with bureaucratic and vertical relations present at the health services. In each group, it was observed that the meanings for health and disease and meanings of the health service the users elaborated can be related. .

OBJETIVO: analisar os significados atribuídos pelos usuários da Atenção Primária à Saúde ao seu processo de saúde/doença e aos serviços utilizados. MÉTODOS: pesquisa qualitativa utilizando a técnica do grupo focal para entrevista com dois grupos de usuários acompanhados pelo serviço, sendo o primeiro um grupo de idosos e o segundo, de mulheres gestantes. Para análise dos significados, usou-se a técnica de análise de discurso e referencial da promoção em saúde. RESULTADOS: grupo de idosos, maioria feminina, portadores de hipertensão arterial e diabetes mellitus, visualiza o processo de saúde/doença como evolução da existência humana controlada pelo poder divino, significando o serviço de saúde como uma bênção no controle da doença. O grupo de gestantes jovens significou saúde como capacidade para autocuidado e doença como incapacidade para tal, concebendo o serviço de Atenção Primária como responsável pela recuperação da saúde individual e familiar. CONSIDERAÇÕES FINAIS: os usuários demonstraram insatisfação com relações burocratizadas e verticalizadas presentes no serviço de saúde. Observou-se, em cada grupo, que significados para saúde e doença e significados do serviço de saúde elaborados pelos usuários podem estar relacionados. .

OBJETIVO: analizar los significados atribuidos por los usuarios de la Atención Primaria de la Salud al proceso salud-enfermedad y a los servicios utilizados. MÉTODOS: investigación cualitativa que utiliza la técnica del grupo focal para entrevistar a dos grupos de usuarios acompañados por el servicio, el primer grupo de ancianos y el segundo de mujeres embarazadas. Para el análisis de los significados, fue usada la técnica de análisis de discurso y el referencial de la promoción de la salud. RESULTADOS: grupo de ancianos, mayoría femenina, con hipertensión arterial y diabetes mellitus, entiende el proceso salud-enfermedad como una evolución de la existencia humana controlada por el poder divino, significando al servicio de salud como una bendición para el control de la enfermedad. Para el Grupo de embarazadas jóvenes significó: la salud como una capacidad para el autocuidado y la enfermedad como la incapacidad para eso, concibiendo al servicio de Atención Primaria como responsable por la recuperación de la salud individual y familiar. CONSIDERACIONES FINALES: los usuarios demostraron insatisfacción con las relaciones burocratizadas y verticales, presentes en el servicio de salud. Se observó en cada grupo que los significados para salud y enfermedad y los significados del servicio de salud elaborados por los usuarios pueden estar relacionados. .

Diethylene glycol in health products sold over-the-counter and imported from Asian countries.

Diethylene glycol (DEG), a chemical that has been implicated in multiple medication-associated mass poisonings, can result in renal and neurological toxicity if ingested. Three previous such mass poisonings implicated Chinese manufacturers as the origin of contaminated ingredients. No literature exists on potential DEG or triethylene glycol (TEG), a related compound, contamination of health products imported from Asian countries to the USA. Our primary objective was to quantitatively assess the amount of DEG present in a convenience sampling of these health products. The study's secondary objectives were to: (1) evaluate for, and quantify TEG levels in these samples; (2) compare DEG and TEG levels in these products directly to levels in medications implicated in previous similar mass poisonings; and (3) to estimate DEG dose (in mg/kg) based on the manufacturer's instructions and compare these values to toxic doses from past mass poisonings and the literature. A quantitative assessment of DEG and TEG was performed in a convenience sampling of over-the-counter health products imported from Asian countries. Results were converted to volume to volume (v/v) % and compared with DEG levels in medications implicated in previous mass poisonings. Estimated doses (based on the manufacturer's instructions) of each product with detectable levels of DEG for a 70 kg adult were compared to toxic doses of DEG reported in the literature. Seventeen of 85 (20%) samples were not able to be analyzed for DEG or TEG due to technical reasons. Fifteen of 68 (22%) samples successfully tested had detectable levels of DEG (mean, 18.8 µg/ml; range, 0.791-110.1 µg/ml; and volume to volume (v/v) range, 0.00007-0.01%). Two of 68 (3%) samples had TEG levels of 12.8 and 20.2 µg/ml or 0.0012% and 0.0018% TEG v/v. The product with the highest DEG% by v/v was 810 times less than the product involved in the Panama DEG mass poisoning (8.1%). The lowest reported toxic dose from a past DEG mass poisoning (14 mg/kg) was more than 150 times higher than the highest daily dose estimated in our study (0.09 mg/kg). Sixty-eight of 85 (80%) samples were able to be successfully analyzed for DEG and TEG. DEG and TEG were detectable in 15/68 (22%) and 2/68 (3%) samples, respectively. Based on current standards, these levels probably do not represent an acute public health threat. Additional research focusing on why DEG is found in these products and on the minimum amount of DEG needed to result in toxicity is needed.

Prospective assessment of short-term propylene glycol tolerance in neonates.

INTRODUCTION: Propylene glycol (PG) is an unintentional frequently administered solvent in neonates despite the fact that PG accumulation potentially results in hyperosmolarity, lactic acidosis and renal/hepatic toxicity. METHODS: Prospective evaluation of renal (diuresis, creatinaemia, sodium), metabolic (base excess, anion gap, lactate, bicarbonate) and hepatic (alanine transaminase, aspartate aminotransferase, direct bilirubinaemia) tolerance to PG in (pre)term neonates following intravenous administration of formulations (paracetamol, phenobarbital, digoxin) that contain PG. Observations from 48 h before up to 48 after the last PG administration were described and compared (paired analysis). Clinical characteristics and observations collected following intravenous PG-paracetamol administration were compared with a historical cohort of neonates in whom similar (renal, hepatic) observations during exposure to a mannitol-containing paracetamol formulation were collected. RESULTS: 5566 observations were collected in 69 neonates before, during and following median PG exposure of 34 mg/kg/24 h (range 14-252). Progressive postnatal adaptation in renal, metabolic and hepatic function was documented, unrelated to the PG exposure. In the subgroup of 40 cases treated with intravenous PG-paracetamol, observations on renal and hepatic function were similar to a historical cohort of published observations following exposure to intravenous mannitol-paracetamol. CONCLUSIONS: Unintended PG administration (34 mg/kg/24 h) for a maximum of 48 h seems to be tolerated in (pre)term neonates and does not affect short-term postnatal adaptations. Further studies on PG disposition and the level of safe exposure to PG, including long-term safety data in neonates are needed.

Final report on the safety assessment of PPG-2 methyl ether, PPG-3 methyl ether, and PPG-2 methyl ether acetate.

PPG-2 methyl ether, PPG-3 methyl ether, and PPG-2 methyl ether acetate are used in cosmetics as fragrance ingredients and/or solvents at concentrations of 0.4% to 2%. Propylene glycol ethers are rapidly absorbed and distributed throughout the body when introduced by inhalation or oral exposure, but the inhalation toxicity of PPG-2 methyl ether vapor, for example, is low. Aerosols, such as found with hair sprays, produce particle sizes that are not respirable. Because these ingredients are highly water-soluble, they are likely to be absorbed through the human skin only at slow rates, resulting in low blood concentrations and rapid removal by the kidney. These ingredients are not genotoxic and are not reproductive or developmental toxicants. Overall the data are sufficient to conclude that PPG-2 methyl ether, PPG-3 methyl ether, and PPG-2 methyl ether acetate are safe as used in cosmetics.

Assessment of reproductive toxicity and gonadotoxic potential of N-methyl-2-pyrrolidone in male rats.

OBJECTIVES: N-methyl-2-pyrrolidone (NMP) is a solvent used in petrochemical, electric and electronic industries, and in the production of paint removers, pesticides and veterinary drugs. The substance exhibits slight acute toxicity, and moderate irritant, embryotoxic and teratogenic effects. The aim of the study was to assess NMP reproductive toxicity and gonadotoxicity in male rats. MATERIAL AND METHODS: The animals were exposed per os to NMP at daily doses of 0, 100, 300 and 1000 mg/kg. After 10 weeks of exposure, each male was mated with nonexposed female, then all the males were autopsied, and epididymis and testis were fixed for pathomorphological examination. Viability and development of offspring was observed to 28 days postbirth. RESULTS: NMP at 1000 mg/kg was found to produce male infertility and extensive damage to the seminiferous epithelium in the seminal tubules of the testis. When administered at 100 mg/kg or 300 mg/kg, it did not significantly affect fertility or spermatogenesis. NMP exposure at 100 mg/kg did not influence either the viability or the development of their offspring in the first month of life, while exposure at 300 mg/kg resulted in a significantly lower viability of the offspring in the first four days of life. CONCLUSION: This study has demonstrated that sub-chronic exposure of male rats to NMP at 1000 mg/kg/day produces gonadotoxic effect and brings about infertility. Administration at lower doses of 100 and 300 mg/kg did not impair male fertility, but only the lowest dose of 100 mg/kg was found to have no influence on the prenatal development of the progeny.

Inhalant misuse in youth: time for a coordinated response.

Early adolescence is associated with high rates of experimental inhalant misuse, but only a minority continue to inhale on a regular basis. Inhalant misuse is associated with a range of adverse outcomes, including reports of increased morbidity and mortality. Research into inhalant use among adolescents is lacking, with limited data available on long-term outcomes or evidence-based approaches to treatment. Legislative and supply-reduction strategies have been introduced by a number of states and territories over recent years, but direct funding for specific targeted interventions is lacking. Investment and commitment to a national research framework, as well as coordination of local services, is urgently required.

A proposed methodology for selecting a trichloroethylene inhalation unit risk value for use in risk assessment.

U.S. EPA's 2001 draft assessment of trichloroethylene (TCE) toxicity reviews the existing human and animal data on TCE carcinogenicity and proposes a 20-fold range of cancer potency values for use in risk assessment. Each value in the range is derived from a different source of data, either animal bioassays or epidemiology studies, and thus the range does not represent a distribution which can be characterized by statistical parameters such as a mean or 95% confidence interval. The U.S. EPA suggests users choose a single slope factor from among those it describes as appropriate for the population of interest and mode of exposure, but little guidance is given for making this choice. We propose an approach for determining the most scientifically defensible carcinogenic inhalation unit risk estimate from the range of slope factors developed by U.S. EPA, one that relies on accepted principles for evaluating scientific studies. Based on these considerations, we identify the most appropriate interim unit risk for low-level inhalation exposure as 9 x 10(-7) per microg/m(3). This approach may have fairly broad utility if U.S. EPA elects to use a similar approach in future assessments of other chemicals.

Reliability of a semi-quantitative method for dermal exposure assessment (DREAM).

Valid and reliable semi-quantitative dermal exposure assessment methods for epidemiological research and for occupational hygiene practice, applicable for different chemical agents, are practically nonexistent. The aim of this study was to assess the reliability of a recently developed semi-quantitative dermal exposure assessment method (DREAM) by (i) studying inter-observer agreement, (ii) assessing the effect of individual observers on dermal exposure estimates for different tasks, and (iii) comparing inter-observer agreement for ranking of body parts according to their exposure level. Four studies were performed in which a total of 29 observers (mainly occupational hygienists) were asked to fill in DREAM while performing side-by-side observations for different tasks, comprising dermal exposures to liquids, solids, and vapors. Intra-class correlation coefficients ranged from 0.68 to 0.87 for total dermal exposure estimates, indicating good to excellent inter-observer agreement. The effects of individual observers on task estimates were estimated using a linear mixed effect model with logged DREAM estimates as explanatory variable; "task", "company/department", and the interaction of "task" and "company/department" as fixed effects; and "observer" as a random effect. Geometric mean (GM) dermal exposure estimates for different tasks were estimated by taking the exponent of the predicted betas for the tasks. By taking the exponent of the predicted observer's intercept (exp(omega i)), a multiplier (M(O)) was estimated for each observer. The effects of individual observers on task estimates were relatively small, as the maximum predicted mean observers' multiplier was only a factor 2, while predicted GMs of dermal exposure estimates for tasks ranged from 0 to 1226, and none of the predicted individual observers' multipliers differed significantly from 1 (t-test alpha = 0.05). Inter-observer agreement for ranking of dermal exposure of nine body parts was moderate to good, as median values of Spearman correlation coefficients for pairs of observers ranged from 0.29 to 0.93. DREAM provides reproducible results for a broad range of tasks with dermal exposures to liquids, solids, as well as vapors. DREAM appears to offer a useful advance for estimations of dermal exposure both for epidemiological research and for occupational hygiene practice.

Analysis of solvent central nervous system toxicity and ethanol interactions using a human population physiologically based kinetic and dynamic model.

The effect of acute ethanol-mediated inhibition of m-xylene metabolism on central nervous system (CNS) depression in the human worker population was investigated using physiologically based pharmacokinetic (PBPK) models and probabilistic random (Monte Carlo) sampling. PBPK models of inhaled m-xylene and orally ingested ethanol were developed and combined by a competitive enzyme (CYP2E1) inhibition model. Human interindividual variability was modeled by combining estimated statistical distributions of model parameters with the deterministic PBPK models and multiple random or Monte Carlo simulations. A simple threshold pharmacodynamic model was obtained by simulating m-xylene kinetics in human studies where CNS effects were observed and assigning the peak venous blood m-xylene concentration (C(V,max)) as the dose surrogate of toxicity. Probabilistic estimates of an individual experiencing CNS disturbances given exposure to the current UK occupational exposure standard (100 ppm time-weighted average over 8 h), with and without ethanol ingestion, were obtained. The probability of experiencing CNS effects given this scenario increases markedly and nonlinearly with ethanol dose. As CYP2E1-mediated metabolism of other occupationally relevant organic compounds may be inhibited by ethanol, simulation studies of this type should have an increasingly significant role in the chemical toxicity risk assessment.

Assessment of occupational exposures in a general population: comparison of different methods.

OBJECTIVES: To evaluate the relative merits of job specific questionnaires and various alternative assessment methods of occupational exposures often used in general population studies. METHODS: Subjects were participants in a hospital based case-control study of risk factors for male infertility. Estimates of exposure to organic solvents and chromium, based on job specific questionnaires, generic questionnaires, self reports of exposure, an external job exposure matrix (JEM), and a population specific JEM were compared with passive diffuse dosimeter results and measurements in urine. Urine samples from the end of the shift were analysed for metabolites of toluene, xylene, several glycol ethers, trichloroethylene, and chromium. Passive dosimeter date, metabolites of specific solvents, and urinary chromium concentrations were available for 89, 267, and 156 subjects, respectively. The alternative methods and measurements in urine were compared by means of the Cohen's kappa statistic and by computing the positive predictive value, sensitivity, and specificity of the alternative methods against measurements in urine. RESULTS: Passive dosimeter results indicated that exposure classifications with job specific questionnaire information could discriminate between high and low exposures. The kappa coefficients were < 0.4, so agreement between the various methods and measurements in urine was poor. Sensitivity of the methods ranged from 0.21 to 0.85, whereas specificity ranged from 0.34 to 0.94. Positive predictive values ranged from 0.19 to 0.58, with the highest values for job specific questionnaires. CONCLUSIONS: The results indicate that the implementation of job specific questionnaires in a general population study might be worth the extra expense it entails, bearing in mind the paramount importance of avoiding false positive exposure estimates when exposure prevalence is low.