Globally resolved surface temperatures since the Last Glacial Maximum.

Climate changes across the past 24,000 years provide key insights into Earth system responses to external forcing. Climate model simulations1,2 and proxy data3-8 have independently allowed for study of this crucial interval; however, they have at times yielded disparate conclusions. Here, we leverage both types of information using paleoclimate data assimilation9,10 to produce the first proxy-constrained, full-field reanalysis of surface temperature change spanning the Last Glacial Maximum to present at 200-year resolution. We demonstrate that temperature variability across the past 24 thousand years was linked to two primary climatic mechanisms: radiative forcing from ice sheets and greenhouse gases; and a superposition of changes in the ocean overturning circulation and seasonal insolation. In contrast with previous proxy-based reconstructions6,7 our results show that global mean temperature has slightly but steadily warmed, by ~0.5 °C, since the early Holocene (around 9 thousand years ago). When compared with recent temperature changes11, our reanalysis indicates that both the rate and magnitude of modern warming are unusual relative to the changes of the past 24 thousand years.

Revision Arthroscopic Bankart Repair Results in High Failure Rates and a Low Return to Duty Rate Without Recurrent Instability.

PURPOSE: The purpose of this study was to determine, in a military population without critical bone loss, the rate of recurrent instability after revision arthroscopic stabilization for failed primary arthroscopic Bankart repair. METHODS: Forty-one revision arthroscopic stabilizations were performed at a single military institution between 2005 to 2016 for recurrent anterior shoulder instability after primary arthroscopic Bankart repair. Minimum follow-up was 2 years, and shoulders with glenoid bone loss >20% were excluded. The primary outcome of interest was the incidence of failure, defined by recurrent instability. RESULTS: Age at revision surgery averaged 22.9 ± 4.3 years, and 88% were either service academy cadets or active duty combat arms soldiers. Mean follow-up was 7.8 years. Twenty-three patients (56%) returned to duty without recurrent instability after revision arthroscopic stabilization. Eighteen patients (44%) experienced recurrent instability after return to duty. Glenoid bone loss averaged 6.2% (95% confidence interval [CI], 3.2%-9.2%) in the successful group and 5.7% (95% CI, 3.1%-8.3%) in the failure group (P = .808). CONCLUSIONS: Revision arthroscopic stabilization of failed primary arthroscopic Bankart repair has a failure rate of 44% in a young military population. The similar amounts of bone loss between groups indicates that bone loss is not the primary determinant of failure in revision arthroscopic stabilization. LEVEL OF EVIDENCE: IV, Case Series.

Full-scale multisampling and empirical modeling of DBPs in water and air of indoor pools.

Disinfection by-products (DBPs) are formed in the water in swimming pools due to reactions between disinfectants (chlorine, bromine, ozone) and the organic matter introduced by bathers and supply water. High concentrations of DBPs are also reported in the air of indoor swimming pools. Based on a robust multisampling program, the levels and variations of DBPs in the air (trichloramine [TCAM] and trihalomethanes [THMs]) and water (THM) were assessed, as well as their precursors (total organic carbon, water temperature, pH, free, and total chlorine) and proxies (CO2 and relative humidity) in four indoor chlorinated swimming pools. High-frequency sampling was conducted during one high-attendance day for each pool. This study focused on parameters that are easy to measure in order to develop models for predicting levels of THMs and TCAM in the air. The results showed that the number of bathers had an important impact on the levels of THMs and TCAM, with a two-to-three-fold increase in air chloroform (up to 110 µg/m3) and a two-to-four-fold increase in TCAM (up to 0.52 mg/m3) shortly after pools opened. The results of this study for the first time showed that CO2 and relative humidity can serve as proxies for monitoring variations in airborne THMs and TCAM. Our results highlight the good predictive capacity of the developed models and their potential for use in day-to-day monitoring. This could help optimize and control DBPs formation in the air of indoor swimming pools and reduce contaminant exposure for both pool employees and users.

Temporal and spatial variations in the levels of prominent airborne disinfection by-products at four indoor swimming pools.

Exposure to airborne disinfection by-products, especially trichloramine and trichloromethane, may cause various adverse health effects for the workers and users of indoor swimming pools. This study aims to evaluate the spatial and temporal variations in trichloramine and trichloromethane concentrations within and between swimming pools. Workplace measurements were carried out at four indoor swimming pools in Quebec (Canada) during the cold season. To fully represent daily operating conditions, sampling started 2 hr before the swimming pool opened and continued until 2 hr after closing. To quantify trichloramine and trichloromethane concentrations, 304 air samples have been collected. Temperature, humidity, and CO2 were measured-simultaneously every 2 hr. The results showed that both trichloramine and trichloromethane concentrations varied significantly in time. The observed daily variations in trichloramine and trichloromethane concentrations suggest that the common practice of collecting a single 2-hr air sample does not represent daily pool trichloramine and trichloromethane contamination levels and, consequently, does not represent the true exposure and health risks for workers that are present for a full 8-hr shift. This study recommends a new 8-hr sampling strategy or a full-shift strategy using a cassette with three impregnated filters as a valid and cost-effective solution for comparing time-weighted average (TWA) concentrations to permissible trichloramine exposure limits.

Concentrations of disinfection by-products in swimming pool following modifications of the water treatment process: An exploratory study.

The formation and concentration of disinfection by-products (DBPs) in pool water and the ambient air vary according to the type of water treatment process used. This exploratory study was aimed at investigating the short-term impact of modifications of the water treatment process on traditional DBP levels (e.g., trihalomethanes (THMs), chloramines) and emerging DBPs (e.g., Halonitromethanes, Haloketones, NDMA) in swimming pool water and/or air. A sampling program was carried to understand the impact of the following changes made successively to the standard water treatment process: activation of ultraviolet (UV) photoreactor, halt of air stripping with continuation of air extraction from the buffer tank, halt of air stripping and suppression of air extraction from the buffer tank, suppression of the polyaluminium silicate sulfate (PASS) coagulant. UV caused a high increase of Halonitromethanes (8.4 fold), Haloketones (2.1 fold), and THMs in the water (1.7 fold) and, of THMs in the air (1.6 fold) and contributed to reducing the level of chloramines in the air (1.6 fold) and NDMA in the water (2.1 fold). The results highlight the positive impact of air stripping in reducing volatile contaminants. The PASS did not change the presence of DBPs, except for the THMs, which decrease slightly with the use of this coagulant. This study shows that modifications affecting the water treatment process can rapidly produce important and variable impacts on DBP levels in water and air and suggests that implementation of any water treatment process to reduce DBP levels should take into account the specific context of each swimming pool.

Assessment of air and water contamination by disinfection by-products at 41 indoor swimming pools.

This study was aimed at assessing the profiles (occurrence and speciation) of disinfection by-product (DBP) contamination in air and water of a group of 41 public indoor swimming pools in Québec (Canada). The contaminants measured in the water included the traditional DBPs [i.e., four trihalomethanes (THMs), six haloacetic acids (HAAs)] but also several emergent DBPs [i.e., halonitriles, halonitromethanes, haloketones and nitrosodimethylamine (NDMA)]. Those measured in the air comprised THMs and chloramines (CAMs). Overall, extremely variable DBP levels were found from one pool to another (both quantitatively and in terms of speciation). For instance, in water, among the four THMs, chloroform was usually the most abundant compound (37.9±25.7µg/L). Nevertheless, the sum of the three other brominated THMs represented more than 25% of total THMs at almost half the facilities visited (19 cases). In 13 of them, the levels of brominated THMs (66±24.2µg/L) even greatly outweighed the levels of chloroform (15.2±6.31µg/L). Much higher levels of HAAs (294.8±157.6µg/L) were observed, with a consistent preponderance of brominated HAAs in the swimming pools with more brominated THMs. NDMA levels which were measured in a subset of 8 pools ranged between 2.8ng/L and 105ng/L. With respect to air, chloroform was still the most abundant THM globally (119.4±74.2µg/m(3)) but significant levels of brominated THMs were also observed in various cases, particularly in the previously evoked group of 13 swimming pools with preponderant levels of brominated THMs in water. CAM levels (0.23±0.15mg/m(3)) varied highly, ranging from not detected to 0.56mg/m(3). Overall, the levels were generally relatively high compared to current guidelines or reference values from several countries, and they point to a relatively atypical presence of brominated compounds, and to significant levels of emergent DBPs for which health risk is less documented.

Evaluation and modeling of the impact of coexposures to VOC mixtures on urinary biomarkers.

CONTEXT: Urinary biomarkers are widely used among biomonitoring studies because of their ease of collection and nonintrusiveness. Chloroform and TEX (i.e., toluene, ethylbenzene, and m-xylene) are chemicals that are often found together because of common use. Although interactions occurring among TEX are well-known, no information exists on possible kinetic interactions between these chemicals and chloroform at the level of parent compound or urinary biomarkers. OBJECTIVE: The objective of this study was therefore to study the possible interactions between these compounds in human volunteers with special emphasis on the potential impact on urinary biomarkers. MATERIALS AND METHODS: Five male volunteers were exposed by inhalation for 6 h to single, binary, and quaternary mixtures that included chloroform. Exhaled air and blood samples were collected and analyzed for parent compound concentrations. Urinary biomarkers (o-cresol, mandelic, and m-methylhippuric acids) were quantified in urine samples. Published PBPK model for chloroform was used, and a Vmax of 3.4 mg/h/kg was optimized to provide a better fit with blood data. Adapted PBPK models from our previous study were used for parent compounds and urinary biomarkers for TEX. RESULTS: Binary exposures with chloroform resulted in no significant interactions. Experimental data for quaternary mixture exposures were well predicted by PBPK models using published description of competitive inhibition among TEX components. However, no significant interactions were observed at levels used in this study. CONCLUSION: PBPK models for urinary biomarkers proved to be a good tool in quantifying exposure to VOC.

Creatinine and specific gravity normalization in biological monitoring of occupational exposures.

Reference values for the biological monitoring of occupational exposures are generally normalized on the basis of creatinine (CR) concentration or specific gravity (SG) to account for fluctuations in urine dilution. For instance, the American Conference of Governmental Industrial Hygienists (ACGIH(®)) uses a reference value of 1g/L for CR. The comparison of urinary concentrations of biomarkers between studies requires the adjustment of results based on a reference CR and/or SG value, although studies have suggested that age, sex, muscle mass, and time of the day can exert non-negligible influences on CR excretion, while SG appears to be less affected. The objective of this study was to propose reference values for urinary CR and SG based on the results of samples sent for analysis by occupational health practitioners to the laboratory of the Occupational Health and Safety Research Institute of Québec (IRSST). We analyzed a database containing 20,395 urinary sample results collected between 1985 and 2010. Linear mixed-effects models with worker as a random effect were used to estimate the influence of sex and collection period on urinary CR and SG. Median CR concentrations were 25-30% higher in men (1.6 g/L or 14.4 mmol/L) than in women (1.2 g/L or 10.2 mmol/L). Four percent of the samples for men and 12% for women were below the acceptable threshold for CR (4.4 mmol/L). For SG, 5% of samples for men and 12% for women were below the threshold of 1.010. The difference in SG levels between sexes was lower than for CR, with a median of 1.024 for men compared to 1.020 for women. Our results suggest that the normalization of reference values based on a standard CR value of 1 g/L as proposed by the ACGIH is a conservative approach. According to the literature, CR excretion is more influenced by physiological parameters than SG. We therefore suggest that correction based on SG should be favored in future studies involving the proposal of reference values for the biological monitoring of occupational exposures.

Ethanol toxicokinetics resulting from inhalation exposure in human volunteers and toxicokinetic modeling.

Uncertainty exists regarding the validity of a previously developed physiologically-based pharmacokinetic model (PBPK) for inhaled ethanol in humans to predict the blood levels of ethanol (BLE) at low level exposures (<1000 ppm). Thus, the objective of this study is to document the BLE resulting from low levels exposures in order to refine/validate this PBPK model. Human volunteers were exposed to ethanol vapors during 4 h at 5 different concentrations (125-1000 ppm), at rest, in an inhalation chamber. Blood and exhaled air were sampled. Also, the impact of light exercise (50 W) on the BLE was investigated. There is a linear relationship between the ethanol concentrations in inhaled air and (i) BLE (women: r²= 0.98/men: r²= 0.99), as well as (ii) ethanol concentrations in the exhaled air at end of exposure period (men: r²= 0.99/women: r²= 0.99). Furthermore, the exercise resulted in a net and significant increase of BLE (2-3 fold). Overall, the original model predictions overestimated the BLE for all low exposures performed in this study. To properly simulate the toxicokinetic data, the model was refined by adding a description of an extra-hepatic biotransformation of high affinity and low capacity in the richly perfused tissues compartment. This is based on the observation that total clearance observed at low exposure levels was much greater than liver blood flow. The results of this study will facilitate the refinement of the risk assessment associated with chronic inhalation of low levels of ethanol in the general population and especially among workers.

Last millennium hurricane activity linked to endogenous climate variability.

Despite increased Atlantic hurricane risk, projected trends in hurricane frequency in the warming climate are still highly uncertain, mainly due to short instrumental record that limits our understanding of hurricane activity and its relationship to climate. Here we extend the record to the last millennium using two independent estimates: a reconstruction from sedimentary paleohurricane records and a statistical model of hurricane activity using sea surface temperatures (SSTs). We find statistically significant agreement between the two estimates and the late 20th century hurricane frequency is within the range seen over the past millennium. Numerical simulations using a hurricane-permitting climate model suggest that hurricane activity was likely driven by endogenous climate variability and linked to anomalous SSTs of warm Atlantic and cold Pacific. Volcanic eruptions can induce peaks in hurricane activity, but such peaks would likely be too weak to be detected in the proxy record due to large endogenous variability.

Rat pulmonary responses to inhaled nano-TiO2: effect of primary particle size and agglomeration state.

BACKGROUND: The exact role of primary nanoparticle (NP) size and their degree of agglomeration in aerosols on the determination of pulmonary effects is still poorly understood. Smaller NP are thought to have greater biological reactivity, but their level of agglomeration in an aerosol may also have an impact on pulmonary response. The aim of this study was to investigate the role of primary NP size and the agglomeration state in aerosols, using well-characterized TiO2 NP, on their relative pulmonary toxicity, through inflammatory, cytotoxic and oxidative stress effects in Fisher 344 male rats. METHODS: Three different sizes of TiO2 NP, i.e., 5, 10-30 or 50 nm, were inhaled as small (SA) (< 100 nm) or large agglomerates (LA) (> 100 nm) at 20 mg/m³ for 6 hours. RESULTS: Compared to the controls, bronchoalveolar lavage fluids (BALF) showed that LA aerosols induced an acute inflammatory response, characterized by a significant increase in the number of neutrophils, while SA aerosols produced significant oxidative stress damages and cytotoxicity. Data also demonstrate that for an agglomeration state smaller than 100 nm, the 5 nm particles caused a significant increase in cytotoxic effects compared to controls (assessed by an increase in LDH activity), while oxidative damage measured by 8-isoprostane concentration was less when compared to 10-30 and 50 nm particles. In both SA and LA aerosols, the 10-30 nm TiO2 NP size induced the most pronounced pro-inflammatory effects compared to controls. CONCLUSIONS: Overall, this study showed that initial NP size and agglomeration state are key determinants of nano-TiO2 lung inflammatory reaction, cytotoxic and oxidative stress induced effects.

ÉquiNanos: innovative team for nanoparticle risk management.

Interactions between nanoparticles (NP), humans and the environment are not fully understood yet. Moreover, frameworks aiming at protecting human health have not been adapted to NP but are nonetheless applied to NP-related activities. Consequently, business organizations currently have to deal with NP-related risks despite the lack of a proven effective method of risk-management. To respond to these concerns and fulfill the needs of populations and industries, ÉquiNanos was created as a largely interdisciplinary provincial research team in Canada. ÉquiNanos consists of eight platforms with different areas of action, from adaptive decision-aid tool to public and legal governance, while including biological monitoring. ÉquiNanos resources aim at responding to the concerns of the Quebec nanotechnology industry and public health authorities. Our mandate is to understand the impact of NP on human health in order to protect the population against all potential risks emerging from these high-priority and rapidly expanding innovative technologies. FROM THE CLINICAL EDITOR: In this paper by Canadian authors an important framework is discussed with the goal of acquiring more detailed information and establishing an infrastructure to evaluate the interaction between nanoparticles and living organisms, with the ultimate goal of safety and risk management of the rapidly growing fields of nanotechnology-based biological applications.

Generating nano-aerosols from TiO2 (5 nm) nanoparticles showing different agglomeration states. Application to toxicological studies.

Agglomeration of nanoparticles (NP) is a key factor in the generation of aerosols from nano-powders and may represent an important parameter to consider in toxicological studies. For this reason, the characterization of NP aerosols (e.g., concentration, size, and structure of agglomerates) is a critical step in the determination of the relationship between exposure and effects. The aim of this study was to generate and characterize aerosols composed of TiO2 (5 nm) NP showing different agglomeration states. Two concentrations were tested: 2 and 7 mg/m³. Stable mass concentrations over 6 hr were successfully generated by a wet method using Collison and Delavan nebulizers that resulted in aerosols composed of smaller agglomerates (<100 nm), while aerosols composed of larger agglomerates (>100 nm) were obtained by dry generation techniques using either a Palas dust feeder or a Fluidized Bed. Particle size distributions in the aerosols were determined by an electrical low pressure impactor. Median number aerodynamic diameters corresponding to the aerosol with smaller and larger agglomerates were 30 and 185 nm, respectively, for the 2 mg/m³ concentration, and 31 and 194 nm for the 7 mg/m³ experiment. Image analysis by transmission electron microscopy showed the presence of compact or agglomerates with void spaces in the different nano-aerosols. These characterized nano-aerosols will be used in further experiments to study the influence of agglomerate size on NP toxicity.

Comparison of sampling collection strategies for assessing airborne trichloramine levels in indoor swimming pools.

Since 1995, Hery's trichloramine sampling procedure has been widely used to determine trichloramine exposure in indoor swimming pools. This method consists of pumping air at a 1 L/min flow rate for 2 h through a Teflon prefilter and two quartz fiber filters. Modified Hery methods have been reported using different sampling pump flow rates and types of prefilters. It is possible that the prefilter type or sample collection pump flow rate influenced the results of these studies. This study is designed to evaluate the effects of different cassette assemblies and sampling flow rates on the levels of measured trichloramine. Laboratory tests were performed using a trichloramine production setup designed for this study. Workplace measurements were carried out at four indoor swimming pools. Different prefiltering strategies were used: no prefilter, glass prefilter or Teflon prefilter in the sampling cassette, and an original separable prefilter cassette is presented in this study. Laboratory tests indicated that at trichloramine concentrations higher than 1 mg/m3, the percentage of trichloramine captured on the first filter could be less than 75%, which demonstrated possible loss of the material during sampling. An investigation of the prefilter effect on the sampling strategy using different cassette assemblies revealed that using a separable cassette assembly prevented overestimations of trichloramine levels. Furthermore, there were no significant differences between trichloramine concentrations measured at flow rates (from 0.5 to 2 L/min) in swimming pools.

Maternal exposure to drinking-water chlorination by-products and small-for-gestational-age neonates.

BACKGROUND: There is concern about possible effects of disinfection by-products on reproductive outcomes. The purpose of this study was to evaluate the association between maternal exposure to chlorination by-products and the risk of delivering a small for-gestational-age (SGA) neonate. METHODS: We conducted a population-based case-control study in the Québec City (Canada) area. Term newborn cases with birth weights <10th percentile (n = 571) were compared with 1925 term controls with birth weights ≥10th percentile. Concentrations of trihalomethanes and haloacetic acids in the water-distribution systems of participants were monitored during the study period, and a phone interview on maternal habits was completed within 3 months after childbirth. We estimated chlorination by-products ingestion during the last trimester of pregnancy and trihalomethanes doses resulting from inhalation and dermal exposure. We evaluated associations between chlorination by-products in utero exposure and SGA by means of unconditional logistic regression with control of potential confounders. RESULTS: When total trihalomethanes and the 5 regulated haloacetic acids concentrations were divided into quartiles, no clear dose-response relationship was found with SGA. However, increased risk was observed when haloacetic concentrations were above the fourth quartile and when either trihalomethanes or haloacetic acids concentrations were above current water standards (adjusted OR= 1.5 [95% confidence interval = 1.1-1.9] and 1.4 [1.1-1.9], respectively). Inhalation and dermal absorption of trihalomethanes did not contribute to this risk, but a monotonic dose-response was found with haloacetic acids ingestion. CONCLUSION: Oral exposure to high levels of chlorination by-products in drinking water could be a risk factor for term SGA.

Oral p-tert-octylphenol exposures induce minimal toxic or estrogenic effects in adult female Sprague-Dawley rats.

Contamination of the environment with endocrine-disrupting chemicals (EDC) has raised concerns about potential health hazards for humans and wildlife. Human and wildlife exposure to one such ubiquitous chemical, p-tert-octylphenol (OP), are likely, due to its persistence in the environment and its presence in food, water, and items of daily use. OP is reported to bind to the estrogen receptor (ER) and alter expression of estrogen-responsive genes. Detrimental effects of OP exposures on the reproductive system have been observed in most, but not all, in vivo experiments. This study examined estrogenic effects of oral exposures of adult female rats to OP. In vitro, OP bound weakly to human ER and a co-activator protein, and accelerated proliferation of MCF-7 cells. Adult Sprague-Dawley rats were given OP by gavage daily for 35 d (25, 50, or 125 mg/kg/d). Body and organ weights and ovarian follicle populations were not significantly altered in OP-exposed adult rats, despite detectable levels of OP in reproductive organs. The estrous cycle of rats was slightly altered, but there were no significant estrogen-like changes in histomorphology or gene expression of the uterus. Prepubertal rats given 125 or 250 mg/kg OP by gavage for 3 d had reduced body weight compared to vehicle-exposed rats but failed to show any uterotrophic response, although 17alpha-ethinyl estradiol (EE, 10 microg/kg/d, ip) induced a threefold increase in uterine weight. Overall, results suggest that toxicity will occur before estrogenic effects with oral exposures to OP. Relevant environmental exposures likely pose little risk for estrogenic effects.

Database for physiologically based pharmacokinetic (PBPK) modeling: physiological data for healthy and health-impaired elderly.

Physiologically based pharmacokinetic (PBPK) models have increasingly been employed in chemical health risk assessments. By incorporating individual variability conferred by genetic polymorphisms, health conditions, and physiological changes during development and aging, PBPK models are ideal for predicting chemical disposition in various subpopulations of interest. In order to improve the parameterization of PBPK models for healthy and health-impaired elderly (herein defined as those aged 65 yr and older), physiological parameter values were obtained from the peer-reviewed literature, evaluated, and entered into a Microsoft ACCESS database. Database records include values for key age-specific model inputs such as ventilation rates, organ volumes and blood flows, glomerular filtration rates, and other clearance-related processes. In total, 528 publications were screened for relevant data, resulting in the inclusion of 155 publications comprising 1051 data records for healthy elderly adults and 115 data records for elderly with conditions such as diabetes, chronic obstructive pulmonary disease (COPD), obesity, heart disease, and renal disease. There are no consistent trends across parameters or their associated variance with age; the gross variance in body weight decreased with advancing age, whereas there was no change in variance for brain weight. The database contains some information to inform ethnic and gender differences in parameters; however, the majority of the published data pertain to Asian (mostly Japanese) and Caucasian males. As expected, the number of records tends to decrease with advancing age. In addition to a general lack of data for parameters in the elderly with various health conditions, there is also a dearth of information on blood and tissue composition in all elderly groups. Importantly, there are relatively few records for alveolar ventilation rate; therefore, the relationship between this parameter and cardiac output (usually assumed to be 1:1) in the elderly is not well informed by the database. Despite these limitations, the database represents a potentially useful resource for parameterizing PBPK models for the elderly to facilitate the prediction of dose metrics in older populations for application in risk assessment.

Effects of chronic exposure to octylphenol on the male rat reproductive system.

p-tert-Octylphenol (OP) is a degradation product of alkylphenol ethoxylates. OP is an endocrine disruptor known to bind to the estrogen receptor; however, effects on males are controversial. The objective of this study was to evaluate the effects of chronic exposure to OP on male reproduction. Adult Sprague-Dawley rats were administered OP for 60 d, representing 1.5 cycles of spermatogenesis. Experimental groups included a vehicle control, and three doses of OP (25, 50, or 125 mg/kg body weight [bw]) administered daily by gavage. There was a significant decrease in body weight in the 125-mg/kg group after 60 d of treatment. Both testicular and epididymal weights and histology were not altered by treatment with OP at any of the doses administered. There were no marked differences in cauda epididymal sperm counts at any doses; however, total percent sperm motility was significantly lower in rats exposed to the intermediate dose (50 mg/kg bw). There was an increase in percent static sperm cells in all OP-treated groups, with the intermediate dose (50 mg/kg) displaying a significantly higher proportion of static cells relative to untreated controls. Caput epididymal sperm motility was unaltered by OP treatment. Gene expression profiles of testes from control and high-dose-exposed rats indicate that 14 genes were modulated by at least twofold, although these changes were not statistically significant. Taken together, results from this study indicate that OP treatment of adult rats does not appear to exert major effects on male reproductive endpoints at relevant environmental exposure doses.

Effect of physical exertion on the biological monitoring of exposure to various solvents following exposure by inhalation in human volunteers: III. Styrene.

This study evaluated the impact of different work load intensities on biological indicators of styrene exposure. Four adult Caucasian men, aged 20 to 44 years, were recruited. Groups of 2-4 volunteers were exposed to 20 ppm of styrene in an exposure chamber according to scenarios involving either aerobic, muscular, or both types of physical exercise for 3 or 7 hr. The target intensities for each 30-min exercise period-interspaced with 15 min at rest-were the following: REST, 38 watts AERO (time-weighted average intensity), 34 watts AERO/MUSC, 49 watts AERO/MUSC, and 54 watts AERO for 7 hr and 22 watts MUSC for 3 hr. End-exhaled air samples were collected at 15 time points during and after 7-hr exposures for the determination of styrene concentrations. Urine samples were collected before the start of exposure, after the first 3 hr of exposure, and at the end of exposure for the determination of mandelic acid (MA) and phenylglyoxilic acid (PGA) concentrations. Compared with exposure at rest, styrene in alveolar air increased by a factor up to 1.7, while the sum of urinary MA and PGA increased by a factor ranging from 1.2 to 3.5, depending on the exposure scenario. Concentrations of biological indicators of styrene fluctuated with physical exertion and were correlated with the magnitude of the physical activity and pulmonary ventilation. Despite the physical exertion effect, urinary concentrations of styrene metabolites after a single-day exposure remain below the current biological exposure index value recommended by ACGIH; therefore, no additional health risk is expected. However, results shows that work load intensities must be considered in the interpretation of biological monitoring data and in the evaluation of the health risk associated with styrene exposure.

The effect of workload on biological monitoring of occupational exposure to toluene and n-Hexane: contribution of physiologically based toxicokinetic modeling.

A physiologically based toxicokinetic model was used to examine the impact of work load on the relationship between the airborne concentrations and exposure indicator levels of two industrial solvents, toluene and n-Hexane. The authors simulated occupational exposure (8 hr/day, 5 days/week) at different concentrations, notably 20 ppm and 50 ppm, which are the current threshold limit values recommended by ACGIH for toluene and n-hexane, respectively. Different levels of physical activity, namely, rest, 25 W, and 50 W (for 12 hr followed by 12 hr at rest) were simulated to assess the impact of work load on the recommended biological exposure indices: toluene in blood prior to the last shift of the workweek, urinary o-cresol (a metabolite of toluene) at the end of the shift, and free (nonhydrolyzed) 2,5-hexanedione (a metabolite of n-hexane) at the end of the shift at the end of the workweek. In addition, urinary excretion of unchanged toluene was simulated. The predicted biological concentrations were compared with the results of both experimental studies among human volunteers and field studies among workers. The highest predicted increase with physical exercise was noted for toluene in blood (39 microg/L at 50 W vs. 14 microg/L at rest for 20 ppm, i.e., a 2.8-fold increase). The end-of-shift urinary concentrations of o-cresol and toluene were two times higher at 50 W than at rest (for 20 ppm, 0.65 vs. 0.33 mg/L for o-cresol and 43 vs. 21 microg/L for toluene). Urinary 2,5-hexanedione predicted for 50 ppm was 1.07 mg/L at 50 W and 0.92 mg/L at rest (+16%). The simulations that best describe the concentrations among workers exposed to toluene are those corresponding to 25 W or less. In conclusion, toxicokinetic modeling confirms the significant impact of work load on toluene exposure indicators, whereas only a very slight effect is noted on n-hexane kinetics. These results highlight the necessity of taking work load into account in risk assessment relative to toluene exposure.