Do cats mirror their owner? Paired exposure assessment using silicone bands to measure residential PAH exposure.

It has been suggested that domestic animals can serve as sentinels for human exposures. In this study our objectives were to demonstrate that i) silicone collars can be used to measure environmental exposures of (domestic) animals, and that ii) domestic animals can be used as sentinels for human residential exposure. For this, we simultaneously measured polycyclic aromatic hydrocarbons (PAHs) using silicone bands worn by 30 pet cats (collar) and their owner (wristband). Collars and wristbands were worn for 7 days and analyzed via targeted Gas Chromatography-Mass Spectrometry (GC-MS). Demographics and daily routines were collected for humans and cats. Out of 16 PAHs, 9 were frequently detected (>50% of samples) in both wristbands and collars, of which Phenanthrene and Fluorene were detected in all samples. Concentrations of wristbands and collars were moderately correlated for these 9 PAHs (Median Spearman's r = 0.51 (range 0.16-0.68)). Determinants of PAH concentrations of cats and humans showed considerable overlap, with vacuum cleaning resulting in higher exposures and frequent changing of bed sheets in lower exposures. This study adds proof-of-principle data for the use of silicone collars to measure (domestic) animal exposure and shows that cats can be used as sentinels for human residential exposure.

Cohort study of workers employed in an Italian tire manufacturing plant, 1962-2004.

PURPOSE: To investigate mortality and bladder cancer incidence among workers of a tire manufacturing plant where antioxidants severely contaminated by beta-naphthylamine were never used. METHODS: Mortality follow-up was performed of 9,501 workers first hired between 1962 when the plant started operations and 2000. Person-years of observation from 1962 to 2004, expected deaths, and standardized mortality ratios (SMR) were calculated. Follow-up for bladder cancer incidence from 1988 to 2003 was carried out, and standardized incidence ratios (SIR) were calculated. Multivariable (Poisson) analyses of bladder cancer incidence and mortality by duration of employment (DOE) and time since first employment (TSFE) were performed. RESULTS: Among men, SMRs were significantly reduced for all causes, all cancers, lung cancer, cardiovascular, and ischemic heart diseases. Bladder cancer mortality and leukemia mortality were close to expectation but increased with TSFE. Seventy-two incident cases of bladder cancer were observed (SIR = 1.15; 95 % confidence interval 0.90-1.44), and multivariable analysis suggested a possible increase in rate ratios with DOE. Among women, mortality was close to expectation, but the limited number of observed deaths prevented detailed analyses. CONCLUSIONS: No significant cancer excess was observed. A suggestion of increased risks of bladder cancer and leukemias after extended TSFE was present in men, deserving consideration as exposure to carcinogens possibly occurred early in plant operation. Furthermore, this cohort of workers is still relatively young and less than 10 % have died. There was, thus, limited power to detect small increases in risk at rare cancer sites. Further epidemiological surveillance of this cohort is planned.

Quantitative assessment of multiple pesticides in silicone wristbands of children/guardian pairs living in agricultural areas in South Africa.

Little is known about personal and time-integrated exposure to past and current used pesticides in agricultural areas and within-family exposure similarities. We aimed to assess exposure to pesticides using silicone wristbands in child/guardian pairs living on farms and in villages within two agricultural areas in South Africa. Using silicone wristbands, we quantified 21 pesticides in child/guardian pairs in 38 households over six days in 2018. Levels (in ng/g wristband) of pesticides and their transformation products (12 current-use pesticides and nine organochlorine pesticides) were measured using GC-MS/MS. We assessed the correlation between pesticide levels and between household members using Spearman correlation coefficients (rs). Multivariable generalized least squares (GLS) models, using household id as intercept, were used to determine level of agreement between household members, exposure differences between children and guardians and exposure predictors (study area, household location [farm vs. village] and household pesticide use). We detected 16 pesticides with highest detection frequencies for deltamethrin (89%), chlorpyrifos (78%), boscalid (56%), cypermethrin (55%), and p,p'-DDT (48%). Most wristbands (92%) contained two or more pesticides (median seven (range one to 12)). Children had higher concentrations than guardians for four pesticides. Correlation between the pesticide levels were in most cases moderate (rs 0.30-0.68) and stronger in children than in guardians. Five pesticides showed moderate to strong correlation between household members, with the strongest correlation for boscalid (rs 0.84). Exposure differences between the two agricultural areas were observed for chlorpyrifos, diazinon, prothiofos, cypermethrin, boscalid, p,p'-DDT and p,p'-DDE and within areas for cypermethrin. We showed that for several pesticides children had higher exposure levels than guardians. The positive correlations observed for child/guardian pairs living in the same household suggest non-occupational shared exposure pathways in these communities.

Calibration of polydimethylsiloxane and polyurethane foam passive air samplers for measuring semi volatile organic compounds using a novel exposure chamber design.

Passive air sampling is increasingly used for air quality monitoring and for personal sampling. In a novel experimental exposure chamber study, 3 types of polydimethylsiloxane (PDMS, including sheet and wristband) and 1 type of polyurethane foam (PUF) passive air samplers were tested for gas-phase uptake of 200 semi volatile organic compounds (SVOCs) during six months. For 155 SVOCs including PAH, PCB, phthalates, organophosphate esters, musk compounds, organochlorine- and other pesticides, a normalized generic uptake rate (Rs) of 7.6 ±â€¯1.3 m3 d-1 dm-2 and a generic mass transfer coefficient (MTC) of 0.87 ±â€¯0.15 cm s-1 at a wind speed of 1.3 m s-1 were determined. Variability of sampling rates within and between passive sampling media and analyte groups was not statistically significant, supporting the hypothesis of air-side controlled uptake regardless of sampling material. A statistical relationship was developed between the sampling rate and windspeed which can be used to obtain a sampling rate applicable to specific deployment conditions. For 98 SVOCs, partition coefficients (Ksampler-air) for PUF and PDMS were obtained, which determine the duration of linear uptake and capacity of the sampler for gas-phase uptake. Ksampler-air for PDMS were approximately 10 times higher than for PUF, suggesting that PDMS can be deployed for longer time per volume of sampler, while uptake remains in the linear phase. Statistical relationships were developed to estimate Kpuf-air and Kpdms-air from Koa. These results improve the understanding of the performance of PDMS and PUF passive samplers and contribute to the development of PDMS for the use as a promising personal sampler.

Polycyclic aromatic hydrocarbon exposure, urinary mutagenicity, and DNA adducts in rubber manufacturing workers.

OBJECTIVES: Several studies have suggested that genotoxic risks might still be present in the contemporary rubber manufacturing industry. Previously, we observed elevated levels of urinary mutagenicity and bladder DNA adducts in rubber workers. Presently, we investigated whether DNA adducts in peripheral blood mononuclear cells (PBMC) and/or urothelial cells may be caused by polycyclic aromatic hydrocarbons or other genotoxic compounds. METHODS: Spot urine samples from 116 rubber manufacturing workers were collected on Sunday and during the workweek (post-shift) to determine 1-hydroxypyrene and mutagenicity levels. For 52 nonsmokers, urothelial cell DNA adducts and PBMC DNA adducts were measured additionally. RESULTS: Urinary 1-hydroxypyrene levels were significantly higher in workweek samples compared with Sunday (P = 0.0001). This increase was not uniform across tasks and only reached statistical significance for the curing department (+99%; P = 0.003). Weekday urinary mutagenicity was significantly increased for mixing (+56%) and curing (+21%) workers when compared with that for Sunday. Total urothelial cell DNA adducts were related to urinary 1-hydroxypyrene (P = 0.021) and mutagenicity (P = 0.027). No significant relationship was found between the adduct levels in PBMC and urothelial cells or between the former and urinary 1-hydroxypyrene or mutagenicity. CONCLUSIONS: Workers in the compounding, mixing, and curing departments were at highest genotoxic risk among rubber manufacturing workers. Increased levels of urinary 1-hydroxypyrene, mutagenicity, and urothelial cell DNA adducts were found in these workers. Urothelial cell and PBMC DNA adducts were not related, hinting possibly to the presence of specific bladder carcinogens in the rubber manufacturing industry.

Urothelial cell DNA adducts in rubber workers.

Workers employed in the rubber industry appear to have a significant excess cancer risk in a variety of sites, including cancer of the urinary bladder. In this cross-sectional study, we investigated the occurrence of DNA adducts in exfoliated bladder cells of currently exposed, nonsmoking rubber workers (n = 52) and their relationship with occupational exposure estimates and acetylation phenotype (NAT2). Four DNA adducts were identified, with the proportion of positive samples (e.g., DNA samples with quantifiable levels of a specific DNA adduct) ranging from 3.8 to 79%. The highest proportion of positive samples and the highest relative adduct labeling levels were in workers involved in the production functions "mixing" and "curing," areas with potential for substantial exposure to a wide range of chemical compounds used in rubber manufacturing (P < 0.05 for adducts 2 and/or 3, compared to all other departments). No statistically significant relationships were found between identified DNA adducts and urinary mutagenicity or personal inhalable and dermal exposure estimates. Interestingly, subjects with a fast NAT2 acetylation phenotype tended to have higher levels of DNA adducts. This study suggests that rubber workers engaged in mixing and curing may be exposed to compounds that can form DNA adducts in urothelial cells. Larger studies among rubber workers should be conducted to study in more detail the potential carcinogenicity of exposures encountered in these work areas.

Carcinogen biomonitoring in human exposures and laboratory research: validation and application to human occupational exposures.

A multiple biomarker approach is required to integrate for metabolism, temporal response and exposure-response kinetics, biological relevance, and positive predictive value. Carcinogen DNA adduct analysis can be used in animal and in vitro studies to detect absorption permutations caused by mixture interactions, and to control metabolic variation when specific CYP450 genes (1A1 or 1A2) are knocked out. These enzymes are not critical to the metabolic activation of model Polycyclic Aromatic Compounds (PAC) and aromatic amines, respectively, as suggested by in vitro analysis. Several human studies have been carried out where multiple biomarkers have been measured. In a study of benzidine workers, the similarities in elimination kinetics between urinary metabolites and mutagenicity is likely responsible for a better correlation between these markers than to BZ-DNA adducts in exfoliated cells. In a study of rubber workers, the relationship between specific departments, urinary 1 HP and DNA adducts in exfoliated cells coincided with the historical urinary bladder cancer risk in these departments; the same relationship did not hold for urinary mutagenicity. In a study of automotive mechanics, biomarkers were used to monitor the effectiveness of exposure interventions. These data reinforce the notion that carcinogen biomarkers are useful to monitor exposure, but that a complementary approaches involving effect and perhaps susceptibility biomarkers is necessary to obtain the necessary information.

2-Naphthol levels and genotoxicity in rubber workers.

Urinary bladder cancer is a historical disease of rubber workers often been associated with exposure to aromatic amines such as 2-naphthylamine. While exposure to these compounds has decreased markedly over time, the bladder cancer risk has not decreased in direct proportion. Polycyclic aromatic compounds (PAC) are candidates for urinary bladder cancer causation. We determined pre- and post-exposure urinary levels of 2-napthol (2NAP), the major metabolite of a model volatile PAC, in a group of non-smoking rubber workers. Pre- and post-exposure urine samples were collected from 43 non-smoking workers. Overall mean post-shift 2-naphthol levels were increased (13.95 ± 28.4 µg/l), but non-significantly compared to samples collected pre-exposure (7.97 ± 22.1 µg/l; p=0.29). The greatest difference was observed in the curing department where post-exposure samples were 4.5 fold higher, post shift samples were significantly higher in production workers as compared to non-production workers (p=0.02). Levels of 2NAP were not correlated with levels of carcinogen-DNA adducts in exfoliated urothelial cells nor with other estimates of exposure or effect. These data suggest that post-shift urinary 2NAP levels are increased, particularly in the curing department. However, the differences were not significantly different overall and urinary 2NAP levels did not predict the level of carcinogen DNA adducts in exfoliated urothelial cells.

Biological monitoring of carbon disulphide and phthalate exposure in the contemporary rubber industry.

OBJECTIVES: We studied the range in urinary levels of 2-thiothiazolidine-4-carboxyl acid (TTCA), a metabolite of CS2 and phthalic acid (PA), a common metabolite of phthalates, across factories and departments in the contemporary rubber manufacturing industry. METHODS: Spot urine samples from 101 rubber workers employed in nine different factories were collected on Sunday and during the workweek on Tuesday, Wednesday and Thursday at approximately 4 pm. In total, 386 urine samples were successfully analyzed. RESULTS: Levels of both biomarkers increased significantly by a factor 2 (paired t-test P-value <0.05) during the working week as compared to the Sunday biomarker levels with absolute increases of approximately 70 microg/l and 5 micromol/mol creatinine for PA and TTCA, respectively. Levels in both biomarkers did not differ markedly between working days. Increases seemed to be restricted to specific factories and/or departments (e.g. molding and curing). CONCLUSIONS: The results of this study demonstrate that rubber workers in the contemporary rubber industry are exposed to phthalates and low levels of CS2 ( approximately 0.05 ppm) as measured by PA and TTCA, respectively. Exposures to both compounds are largely driven by specific circumstances in factories. Therefore, when estimating exposures to phthalates and CS2 detailed information should be collected on the type and amount of phthalate containing ester plasticizers, dithiocarbamates and thiurams used. Preferably, personal exposure data should be collected. In this case, biological monitoring seems a reasonable approach. However, in the case of PA attention should be given to individual background levels as this could lead to a substantial overestimation of the occupational contribution to total phthalate exposure.

A database of exposures in the rubber manufacturing industry: design and quality control.

The concerted action EXASRUB was initiated to create a database management system for information on occupational hygiene measurements that could be used to develop exposure models in the European rubber manufacturing industry. Quality of coding was assessed by calculating percentages of agreement and Cohen's kappa statistics (kappa) for an intra- and inter-centre recoding of randomly selected subsets of the measurements. In a 6-month period, 59 609 measurements from 523 surveys in 333 factories from as early as 1956 to 2003 were coded. The database consists primarily of measurements of N-nitrosamines (36%), rubber dust (23%), solvents (14%) and rubber fumes (10%). Coding of epidemiologically relevant information was done consistently with inter-centre kappa between 0.86 and 1.00. For occupational hygiene information, values of kappa were estimated to be between 0.67 and 1.00. The proposed method resulted in a large quantity of exposure measurements with auxiliary information of varying completeness and quality. Analyses showed that coding of epidemiologically relevant information in such a multi-centre, multi-country study was coded consistently. Larger errors however, occurred in coding of occupational hygiene information. This was primarily caused by lack of information in the primary records of measurements, emphasizing the importance of having a universal system in place to collect and store measurement information by occupational hygienists for future use.