Toxicity and human health assessment of an alcohol-to-jet (ATJ) synthetic kerosene developed under an international agreement with Sweden.

Alcohol-to-jet (ATJ) Synthetic Kerosene with Aromatics (SKA) fuels are produced by dehydration and refining of alcohol feed stocks. ATJ SKA fuel known as SB-8 was developed by Swedish Biofuels as a cooperative agreement between Sweden and AFRL/RQTF. SB-8 including standard additives was tested in a 90-day toxicity study with male and female Fischer 344 rats exposed to 0, 200, 700, or 2000 mg/m3 fuel in an aerosol/vapor mixture for 6 hr/day, 5 days/week. Aerosols represented 0.04 and 0.84% average fuel concentration in 700 or 2000 mg/m3 exposure groups. Examination of vaginal cytology and sperm parameters found no marked changes in reproductive health. Neurobehavioral effects were increased rearing activity (motor activity) and significantly decreased grooming (functional observational battery) in 2000 mg/m3 female rats. Hematological changes were limited to elevated platelet counts in 2000 mg/m3 exposed males. Minimal focal alveolar epithelial hyperplasia with increased number of alveolar macrophages was noted in some 2000 mg/m3 males and one female rat. Additional rats tested for genotoxicity by micronucleus (MN) formation did not detect bone marrow cell toxicity or alterations in number of MN; SB-8 was not clastogenic. Inhalation results were similar to effects reported for JP-8. Both JP-8 and SB fuels were moderately irritating under occlusive wrapped conditions but slightly irritating under semi-occlusion. Exposure to SB-8, alone or as 50:50 blend with petroleum-derived JP-8, is not likely to enhance adverse human health risks in the military workplace.

Parity and the risk of incident dementia: a COSMIC study.

AIMS: To investigate the association between parity and the risk of incident dementia in women. METHODS: We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). RESULTS: Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1-4 parities (HR = 1.30, 95% CI = 1.02-1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02-1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00-2.55), but the risk of AD was not significantly associated with parity. CONCLUSIONS: Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

Epidemiology of suicidal feelings in an ageing Swedish population: from old to very old age in the Gothenburg H70 Birth Cohort Studies.

AIMS: The first aim of this study was to provide prevalence suicidal feelings over time (past week, past month, past year and lifetime) in a population-based sample of old to very old adults without dementia. Does prevalence change with rising age? The second aim was to examine the fluctuation of suicidal feelings over time. How does this coincide with depression status? METHODS: Data were derived from the Gothenburg H70 Birth Cohort Studies (the H70 studies) which are multidisciplinary longitudinal studies on ageing. A representative sample of adults in Gothenburg, Sweden with birth years 1901-1944 were invited to take part in a longitudinal health study on ageing and participated at one or more occasions during 1986-2014. The sample consisted of 6668 observations originating from 3972 participants without dementia between the ages of 70 and 108, including 1604 participants with multiple examination times. Suicidal feelings were examined during a psychiatric interview using the Paykel questions (life not worth living, death wishes, thoughts of taking own life, seriously considered taking life, attempted suicide). RESULTS: Prevalence figures for suicidal feelings of any severity were as follows: past week 4.8%, past month 6.7%, past year 11.2% and lifetime 25.2%. Prevalence rates increased with age in the total group and in women but not in men. Suicidal feelings were common in participants with concurrent major or minor depression, but over a third of the participants who reported suicidal feelings did not fulfil criteria for these diagnoses nor did they present elevated mean depressive symptom scores. The majority of participants consistently reported no experience of suicidal feelings over multiple examination times, but fluctuation was more common in women compared with men. CONCLUSION: Suicidal feelings in late-life are uncommon in individuals without depression indicating that such behaviour is not a widespread, normative phenomenon. However, such feelings may occur outside the context of depression.

Improved predictive model for n-decane kinetics across species, as a component of hydrocarbon mixtures.

n-Decane is considered a major component of various fuels and industrial solvents. These hydrocarbon products are complex mixtures of hundreds of components, including straight-chain alkanes, branched chain alkanes, cycloalkanes, diaromatics, and naphthalenes. Human exposures to the jet fuel, JP-8, or to industrial solvents in vapor, aerosol, and liquid forms all have the potential to produce health effects, including immune suppression and/or neurological deficits. A physiologically based pharmacokinetic (PBPK) model has previously been developed for n-decane, in which partition coefficients (PC), fitted to 4-h exposure kinetic data, were used in preference to measured values. The greatest discrepancy between fitted and measured values was for fat, where PC values were changed from 250-328 (measured) to 25 (fitted). Such a large change in a critical parameter, without any physiological basis, greatly impedes the model's extrapolative abilities, as well as its applicability for assessing the interactions of n-decane or similar alkanes with other compounds in a mixture model. Due to these limitations, the model was revised. Our approach emphasized the use of experimentally determined PCs because many tissues had not approached steady-state concentrations by the end of the 4-h exposures. Diffusion limitation was used to describe n-decane kinetics for the brain, perirenal fat, skin, and liver. Flow limitation was used to describe the remaining rapidly and slowly perfused tissues. As expected from the high lipophilicity of this semivolatile compound (log K(ow) = 5.25), sensitivity analyses showed that parameters describing fat uptake were next to blood:air partitioning and pulmonary ventilation as critical in determining overall systemic circulation and uptake in other tissues. In our revised model, partitioning into fat took multiple days to reach steady state, which differed considerably from the previous model that assumed steady-state conditions in fat at 4 h post dosing with 1200 ppm. Due to these improvements, and particularly the reconciliation between measured and fitted partition coefficients, especially fat, we have greater confidence in using the proposed model for dose, species, and route of exposure extrapolations and as a harmonized model approach for other hydrocarbon components of mixtures.