1,3-Butadiene, styrene and lymphohaematopoietic cancers among North American synthetic rubber polymer workers: exposure-response analyses.

OBJECTIVE: To evaluate exposure-response between 1,3-butadiene, styrene and lymphohaematopoietic cancers in an updated cohort of workers at six North American plants that made synthetic rubber polymers. METHODS: Employees were followed from 1943 through 2009 to determine mortality outcomes. Cox regression analyses estimated rate ratios (RRs) and 95% CIs by quartile of cumulative exposure to butadiene or styrene, measured in parts per million-years (ppm-years), and exposure-response trends for all leukaemia, lymphoid leukaemia, myeloid leukaemia, acute myeloid leukaemia, non-Hodgkin's lymphoma (NHL), multiple myeloma and all B-cell malignancies. RESULTS: Among 21 087 workers, adjusted RRs for butadiene and all leukaemia (132 deaths) rose with increasing exposure, with an RR of 2.53 (95% CI 1.37 to 4.67) in the highest exposure quartile (≥363.64 ppm-years), and the exposure-response trend was statistically significant for all leukaemia (p=0.014) and for lymphoid leukaemia (52 deaths, p=0.007). Styrene exposure-response trends for all leukaemia and lymphoid leukaemia were less consistent than those for butadiene. Cumulative exposures to butadiene and styrene were not associated consistently with myeloid leukaemias or the B-cell malignancies, NHL and multiple myeloma. CONCLUSIONS: We confirmed a positive exposure-response relationship between butadiene and all leukaemia among workers, most of whom had coexposure to styrene. Results supported an association between butadiene and lymphoid leukaemia, but not myeloid leukaemia, and provided little evidence of any association of butadiene or styrene exposures with major subtypes of B-cell malignancies other than lymphoid leukaemia, including NHL and multiple myeloma.

A critical review and meta-analysis of epidemiology studies of occupationally exposed styrene workers evaluated for chromosomal aberration incidence.

Chromosome aberrations in the peripheral blood lymphocytes of styrene exposed workers have been suggested as a potential early marker for cancer risk. We performed a critical review and abstracted data from all studies using current chromosome aberration scoring criteria and providing at least a mean and standard deviation or standard error for the exposed and comparison groups. Using these data, we conducted a meta-analysis of occupational styrene exposed workers and incidence of chromosome aberrations. Our meta-analysis used the standardized mean difference as the summary statistic since all studies assess the same outcome but use different comparison populations. The primary meta-analysis of the 20 comparisons of 505 styrene exposed workers to 532 comparison workers found a meta-mean difference of 0.361 (95 % CI -0.084 to 0.807, random effects model), but there was substantial lack of consistency across studies (I2 of 90.11, p-value <0.001, fixed effect model). Studies with higher styrene exposures had lower mean standard differences compared to studies with lower styrene exposures. While studies of styrene workers overall had a slight increase in chromosomal aberrations relative to comparison groups, the lack of consistency across studies and the absence of an exposure response and other limitations of the reviewed studies including inadequate exposure assessment, small numbers of participants per study, and poorly matched exposed and comparison workers, we find insufficient evidence to support a conclusion that styrene exposure increases chromosome aberration frequencies in styrene workers.

Integrated QSAR and Adverse Outcome Pathway Analysis of Chemicals Released on 3D Printing Using Acrylonitrile Butadiene Styrene.

Additive manufacturing commonly known as 3D printing has numerous applications in several domains including material and biomedical technologies and has emerged as a tool of capabilities by providing fast, highly customized, and cost-effective solutions. However, the impact of the printing materials and chemicals present in the printing fumes has raised concerns about their adverse potential affecting humans and the environment. Thus, it is necessary to understand the properties of the chemicals emitted during additive manufacturing for developing safe and biocompatible fibers having controlled emission of fumes including its sustainable usage. Therefore, in this study, we have developed a computational predictive risk-assessment framework on the comprehensive list of chemicals released during 3D printing using the acrylonitrile butadiene styrene (ABS) filament. Our results showed that the chemicals present in the fumes of the ABS-based fiber used in additive manufacturing have the potential to lead to various toxicity end points such as inhalation toxicity, oral toxicity, carcinogenicity, hepatotoxicity, and teratogenicity. Moreover, because of their absorption, distribution in the body, metabolism, and excretion properties, most of the chemicals exhibited a high absorption level in the intestine and the potential to cross the blood-brain barrier. Furthermore, pathway analysis revealed that signaling like alpha-adrenergic receptor signaling, heterotrimeric G-protein signaling, and Alzheimer's disease-amyloid secretase pathway are significantly overrepresented given the identified target proteins of these chemicals. These findings signify the adversities associated with 3D printing fumes and the necessity for the development of biodegradable and considerably safer fibers for 3D printing technology.

Associations of Occupational Styrene Exposure With Risk of Encephalopathy and Unspecified Dementia: A Long-Term Follow-up Study of Workers in the Reinforced Plastics Industry.

Exposure to industrial solvents has been associated with encephalopathy. Styrene is a neurotoxic industrial solvent, and we investigated the long-term risk of encephalopathy and unspecified dementia following styrene exposure. We followed 72,465 workers in the reinforced plastics industry in Denmark (1977-2011) and identified incident cases of encephalopathy (n = 228) and unspecified dementia (n = 565) in national registers. Individual styrene exposure levels were modeled from information on occupation, measurements of work place styrene levels, product, process, and years of employment. Adjusted analyses were performed using a discrete survival function. A positive trend for encephalopathy (P < 0.01) and a negative trend for unspecified dementia (P = 0.03) were seen with cumulative styrene exposure accrued during the recent period of up to 15 years. For unspecified dementia and the combination of unspecified dementia and encephalopathy, a positive trend was indicated when applying a 30-year exposure lag (P = 0.13 and P = 0.07). The risk patterns seen following recent exposure probably reflect diagnostic criteria for encephalopathy requiring recent industrial solvent exposure and referral bias rather than association with styrene exposure, while the increasing risk observed for unspecified dementia and the combination of encephalopathy and unspecified dementia following distant exposure indicates an increased risk of dementia following styrene exposure with a long latency period.

Exposure to lead, mercury, styrene, and toluene and hearing impairment: evaluation of dose-response relationships, regulations, and controls.

The risk of hearing loss from exposure to ototoxic chemicals is not reflected in occupational exposure limits and most jurisdictions. The aims of this research were to investigate dose-response relationships between exposure to lead, mercury, toluene, and styrene and hearing impairment based on current epidemiological evidence, conduct cross-jurisdictional comparisons, and investigate control measures for exposure to ototoxic chemicals. Ovid Medline and Ovid Embase databases were used to find relevant publications. A total of 86 epidemiological studies met the eligibility criteria for final evaluation. When significant associations between exposure and outcome were identified, exposure levels were evaluated to determine whether No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) could be identified. Cross-jurisdictional comparisons included the U.K., U.S., Canada, and Australia occupational health and safety legislations. The majority of lead (75%), styrene (74%), and toluene (77%) studies showed significantly increased risks of hearing loss from exposure to these substances, although numerous studies on toluene (70%) and styrene (16%) compared auditory function between "solvent mixture" or "noise and solvent mixture" exposed groups and controls and not necessarily on groups exposed to a single agent. Based on five studies, blood lead ranges of 1-1.99 µg/dL to 2.148-2.822 µg/dL were identified as NOAELs while blood lead levels of 2 µg/dL up to 2.823-26.507 µg/dL were identified as LOAELs for hearing loss. Except for general duty clauses, the U.S., Canadian, and Australian jurisdictions have set no enforceable regulations specific to ototoxic chemical exposures. A biological exposure index of 2 µg/dL is recommended for prevention of hearing impairment from lead exposure. Based on Safe Work Australia, noise exposure limits may be reduced to 80 dB(A) for 8 hr. Other recommendations include performing audiometric testing and controlling exposure through all routes of entry.

Exposure-response assessment of cancer mortality in styrene-exposed boatbuilders.

OBJECTIVES: To improve exposure estimates and reexamine exposure-response relationships between cumulative styrene exposure and cancer mortality in a previously studied cohort of US boatbuilders exposed between 1959 and 1978 and followed through 2016. METHODS: Cumulative styrene exposure was estimated from work assignments and air-sampling data. Exposure-response relationships between styrene and select cancers were examined in Cox proportional hazards models matched on attained age, sex, race, birth cohort and employment duration. Models adjusted for socioeconomic status (SES). Exposures were lagged 10 years or by a period maximising the likelihood. HRs included 95% profile-likelihood CIs. Actuarial methods were used to estimate the styrene exposure corresponding to 10-4 extra lifetime risk. RESULTS: The cohort (n= 5163) contributed 201 951 person-years. Exposures were right-skewed, with mean and median of 31 and 5.7 ppm-years, respectively. Positive, monotonic exposure-response associations were evident for leukaemia (HR at 50 ppm-years styrene = 1.46; 95% CI 1.04 to 1.97) and bladder cancer (HR at 50 ppm-years styrene =1.64; 95% CI 1.14 to 2.33). There was no evidence of confounding by SES. A working lifetime exposure to 0.05 ppm styrene corresponded to one extra leukaemia death per 10 000 workers. CONCLUSIONS: The study contributes evidence of exposure-response associations between cumulative styrene exposure and cancer. Simple risk projections at current exposure levels indicate a need for formal risk assessment. Future recommendations on worker protection would benefit from additional research clarifying cancer risks from styrene exposure.

A follow-up study of occupational styrene exposure and risk of autoimmune rheumatic diseases.

OBJECTIVES: Increased risk has been suggested for autoimmune rheumatic diseases following solvent exposure. The evidence for specific solvents is limited, and little is known about exposure-response relations. Styrene is an aromatic, organic solvent and the objective of this study was to analyse the association between occupational styrene exposure and autoimmune rheumatic diseases in men and women. METHODS: We followed 72 212 styrene-exposed workers of the Danish reinforced plastics industry from 1979 to 2012. We modelled full work history of styrene exposure from employment history, survey data and historical styrene exposure measurements. We identified cases in the national patient registry and investigated gender-specific exposure-response relations by cumulative styrene exposure for different exposure time windows adjusting for age, calendar year and educational level. RESULTS: During 1 515 126 person-years of follow-up, we identified 718 cases of an autoimmune rheumatic disease, of which 73% were rheumatoid arthritis. When adjusting for potential confounders and comparing the highest with the lowest styrene exposure tertile, we observed a statistically non-significantly increased risk of systemic sclerosis among women (incidence rate ratio (IRR)=2.50; 95% CI 0.50 to 12.50) and men (IRR=1.86; 95 % CI 0.50 to 7.00), based on 9 and 22 cases, respectively. Results were inconsistent for the other autoimmune rheumatic diseases examined. CONCLUSION: This study suggests an association between occupational styrene exposure and systemic sclerosis in men as well as in women but based on few cases. This is a new finding and has to be replicated before conclusions can be drawn.

Mortality Among Men and Women in the North American Synthetic Rubber Industry, 1943 to 2009.

OBJECTIVE: To evaluate 1943 to 2009 mortality among 22,785 synthetic rubber industry employees. METHODS: Standardized mortality ratio (SMR) and internal Cox regression analyses. RESULTS: Among hourly employees with more than or equal to 10 years worked and more than or equal to 20 years since hire, SMRs were elevated for leukemia (SMR = 139, 95% confidence interval [CI] = 106 to 179), non-Hodgkin lymphoma (NHL) (SMR = 136, CI = 102 to 177), bladder cancer (SMR = 148, CI = 110 to 195) and, for women only, lung cancer (SMR = 225, CI = 103 to 427). Butadiene and styrene exposure-response trends were positive for leukemia and bladder cancer but not for NHL or for lung cancer among women. CONCLUSIONS: Results support a causal relationship between butadiene and leukemia. Interpretation of results for lung cancer among women and for bladder cancer is uncertain because of inability to control for smoking and inadequate or inconsistent support from other studies for an association between butadiene or styrene and the latter cancers.

Environmental Styrene Exposure and Sensory and Motor Function in Gulf Coast Residents.

BACKGROUND: Although styrene is an established neurotoxicant at occupational exposure levels, its neurotoxicity has not been characterized in relation to general population exposures. Further, occupational research to date has focused on central nervous system impairment. OBJECTIVE: We assessed styrene-associated differences in sensory and motor function among Gulf coast residents. METHODS: We used 2011 National Air Toxics Assessment estimates of ambient styrene to determine exposure levels for 2,956 nondiabetic Gulf state residents enrolled in the Gulf Long-term Follow-up Study, and additionally measured blood styrene concentration in a subset of participants 1 to 2 y after enrollment ([Formula: see text]). Participants completed an enrollment telephone interview and a comprehensive test battery to assess sensory and motor function during a clinical follow-up exam 2 to 4 y later. Detailed covariate information was ascertained at enrollment via telephone interview. We used multivariate linear regression to estimate continuous differences in sensory and motor function, and log-binomial regression to estimate prevalence ratios for dichotomous outcomes. We estimated associations of both ambient and blood styrene exposures with sensory and motor function, independently for five unique tests. RESULTS: Those participants in the highest 25% vs. lowest 75% of ambient exposure and those in the highest 10% vs. lowest 90% of blood styrene had slightly diminished visual contrast sensitivity. Mean vibrotactile thresholds were lower among those in the highest vs. lowest quartile of ambient styrene and the highest 10% vs. lowest 90% of blood styrene ([Formula: see text] log microns; 95% CI: [Formula: see text], [Formula: see text] and [Formula: see text] log microns; 95% CI: [Formula: see text], [Formula: see text], respectively). The highest vs. lowest quartile of ambient styrene was associated with significantly poorer postural stability, and (unexpectedly) with significantly greater grip strength. DISCUSSION: We observed associations between higher styrene exposure and poorer visual, sensory, and vestibular function, though we did not detect associations with reduced voluntary motor system performance. Associations were more consistent for ambient exposures, but we also found notable associations with measured blood styrene. https://doi.org/10.1289/EHP3954.

Critical review of styrene genotoxicity focused on the mutagenicity/clastogenicity literature and using current organization of economic cooperation and development guidance.

Styrene is an important high production volume chemical used to manufacture polymeric products. In 2018, International Agency for Research on Cancer classified styrene as probably carcinogenic to humans; National Toxicology Program lists styrene as reasonably anticipated to be a human carcinogen. The genotoxicity literature for styrene and its primary metabolite, styrene 7,8-oxide (SO), begins in the 1970s. Organization of Economic Cooperation and Development (OECD) recently updated most genotoxicity test guidelines, making substantial new recommendations for assay conduct and data evaluation for the standard mutagenicity/clastogenicity assays. Thus, a critical review of the in vitro and in vivo rodent mutagenicity/clastogenicity studies for styrene and SO, based on the latest OECD recommendations, is timely. This critical review considered whether a study was optimally designed, conducted, and interpreted and provides a critical assessment of the evidence for the mutagenicity/clastogenicity of styrene/SO. Information on the ability of styrene/SO to induce other types of genotoxicity endpoints is summarized but not critically reviewed. We conclude that when styrene is metabolized to SO, it can form DNA adducts, and positive in vitro mutagenicity/clastogenicity results can be obtained. SO is mutagenic in bacteria and the in vitro mouse lymphoma gene mutation assay. No rodent in vivo mutation studies were identified. SO is clastogenic in cultured mammalian cells. Although the in vitro assays gave positive responses, styrene/SO is not clastogenic/aneugenic in vivo in rodents. In addition to providing updated information for styrene, this review demonstrates the application of the new OECD guidelines for chemicals with large genetic toxicology databases where published results may or may not be reliable. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

Occupational exposure to benzene, toluene, xylene and styrene and risk of prostate cancer in a population-based study.

OBJECTIVES: While several monocyclic aromatic hydrocarbons are classified as definite or possible carcinogens to humans, little data exist on their role in prostate cancer (PCa). We examined occupational exposure to benzene, toluene, xylene (BTX) and styrene and PCa risk in a population-based case-control study in Montreal, Canada. METHODS: Cases aged ≤75 years diagnosed with PCa in 2005-2009 (n=1920) and population controls frequency-matched on age (n=1989) provided detailed work histories. Experts evaluated the certainty, frequency and concentration of exposure to monocyclic aromatic hydrocarbons in each job lasting ≥2 years. Logistic regression estimated OR and 95% CIs for PCa risk, adjusting for potential confounders. RESULTS: Exposures to BTX were highly intercorrelated, except for durations of exposure at substantial levels. Ever exposure to any BTX was associated with overall PCa (OR 1.27, 95% CI 1.05 to 1.53), while the OR for styrene was 1.19. However, increases in risk were largely confined to low-grade tumours, with ORs of 1.33 (95%CI 1.08 to 1.64) and 1.41 (95% CI 0.85 to 2.31) for ever exposure to any BTX and styrene, respectively, and a duration response pattern for any BTX. Risks for low-grade tumours were elevated among men exposed ≥25 years at substantial levels of benzene (OR 2.32) and styrene (OR 2.44). Some cumulative exposure categories showed increased risks but without clear trends. CONCLUSION: Exposure to any BTX was associated with higher risks of overall PCa. Prolonged exposures at the substantial level to benzene and styrene increased risks of low-grade tumours. These novel findings were independent from PCa screening.

Biomonitoring of styrene occupational exposures: Biomarkers and determinants.

INTRODUCTION: High styrene exposures are still experienced in various occupational settings, requesting regular exposure assessments. The aims of this study were to study occupational exposures in various industrial sectors and to determine factors influencing styrene urinary metabolites levels. METHODS: Biomonitoring was conducted in 141 workers from fiberglass-reinforced plastic (FRP) manufacture, thermoplastic polymers production, vehicle repair shops and cured-in-place pipe lining (CIPP). Urinary styrene (StyU) as well as Mandelic (MA) / Phenyglyoxylic Acids (PGA) were quantified at the beginning and at the end of week, and multivariate linear regression models were used. RESULTS: StyU levels revealed very low, rarely exceeding 3 µg.L-1. Highest concentrations of MA + PGA were observed in FRP sector, with levels reaching up to 1100 mg.g-1 of creatinine. Factors influencing end-of-week MA + PGA concentrations were levels at the beginning of week, open molding processes, proximity to the emission source, respiratory protection, styrene content in raw materials. Elevated levels were also observed during CIPP process, whereas thermoplastic injection and vehicle repair shop workers exhibited much lower exposures. CONCLUSIONS: Intervention on process (decreasing styrene proportion, using closed molding), protective equipment (local exhaust ventilation, respiratory protection) and individual practices (stringent safety rules) are expected to decrease occupational exposures. Urinary MA + PGA remain the most appropriate biomarkers for occupational biomonitoring.

Biomarkers of early genotoxicity and oxidative stress for occupational risk assessment of exposure to styrene in the fibreglass reinforced plastic industry.

This study aimed to identify sensitive and not-invasive biomarkers of early genotoxic/oxidative effect for exposure to styrene in the fibreglass reinforced plastic manufacture. We studied 11 workers of a plastic manufacture using open molding process (A), 16 workers of a manufacture using closed process (B) and 12 controls. We evaluated geno/cytotoxic effects on buccal cells by Buccal Micronucleus Cytome (BMCyt) assay and genotoxic/oxidative effects on lymphocytes by Fpg-comet test. On A workers we also evaluated urinary 8oxoGua, 8oxodGuo and 8oxoGuo to investigate oxidative stress. Personal inhalation exposure to styrene was monitored by passive air sampling and GC/MS. Biological monitoring included urinary metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA). The findings show higher styrene exposure, urinary MA + PGA levels and micronucleus frequency in manufacture A. Higher buccal karyolytic cell frequency vs controls were found in both exposed populations. We found in exposed workers, no induction of direct DNA damage but oxidative DNA damage. Fpg-comet assay and urinary oxidized guanine seem to be sensitive biomarkers of oxidative stress and BMCyt assay a good-not invasive biomarker of cyto-genotoxicity at target organ. The study, although limited by the small number of studied subjects, shows the usefulness of used biomarkers in risk assessment of styrene-exposed workers.

Styrene Exposure and Risk of Lymphohematopoietic Malignancies in 73,036 Reinforced Plastics Workers.

BACKGROUND: Styrene is an important industrial chemical that the general population is exposed to at low levels. Previous research has suggested increased occurrence of leukemia and lymphoma among reinforced plastics workers exposed at high levels of styrene. METHODS: We followed 73,036 workers of 456 small- and medium-sized Danish reinforced plastics companies from 1968 to 2011 and investigated the exposure-response relation between cumulative styrene exposure and incidence of lymphohematopoietic malignancies. We modeled styrene exposure from employment history, survey data, and historical styrene exposure measurements. We retrieved information on lymphohematopoietic malignancies from national cancer and patient registers. RESULTS: We identified 665 cases overall of 21 different lymphohematopoietic malignancies or combinations thereof, each with at least 20 cases, during 1,581,976 person-years of follow-up. Initial analyses suggested higher age, sex, and calendar year-adjusted incidence rate ratios (RRs) for acute myeloid leukemia, Hodgkin lymphoma, and T-cell lymphoma with higher estimates of cumulative styrene exposure. Accounting for time since exposure showed a trend by cumulative styrene exposure (P = 0.01) and a doubled risk (RR = 2.4; 95% CI, 1.2, 4.6) of acute myeloid leukemia following estimated high compared with estimated low cumulative exposure during the prior 15-29 years. We observed no increased risk following exposure during more recent years and less consistent risk patterns for Hodgkin lymphoma and T-cell lymphoma. CONCLUSIONS: This study, to our knowledge the largest epidemiologic study to date of occupational styrene exposure, suggests increased risk of acute myeloid leukemia following high styrene exposure with a latency period of about 15 years.

Sinonasal adenocarcinoma following styrene exposure in the reinforced plastics industry.

BACKGROUND: Sinonasal adenocarcinoma is a rare disease expected to have rare causes and potential for strong risk factors as reflected by the strong association with occupational wood dust exposure. High level styrene exposure is a rare and suspected carcinogen, and this study examines the exposure-response relation between occupational styrene exposure, sinonasal adenocarcinoma and other subtypes. METHODS: We followed 73 092 styrene-exposed workers from 1968 to 2011 and identified sinonasal cancers in the Danish Cancer Registry. We modelled cumulative styrene exposure and estimated incidence rates and age, sex and wood-industry adjusted ORs. RESULTS: During 1 585 772 person-years, we observed nine cases of adenocarcinoma, corresponding to a fivefold non-significantly increased OR for estimates of high versus low cumulative styrene exposure (OR 5.11, 95% CI 0.58 to 45.12). The increased risk was confined to exposure received during the recent 15 years. The other histological subtypes showed no increased risk. CONCLUSION: This study suggests increased risk of sinonasal adenocarcinoma following styrene exposure. The observations are, however, few, confounding from wood dust exposure cannot be ruled out, and additional studies are needed before firm conclusions can be drawn.

Cancer incidence among boat-building workers exposed to styrene.

BACKGROUND: A cancer incidence analysis was conducted on The National Institute for Occupational Safety and Health boat-builders cohort exposed to styrene, a possible carcinogen. METHODS: Standardized incidence ratios (SIR) and standardized rate ratios (SRR) were calculated using national and Washington State rates and a person-years analysis program. RESULTS: Among 3704 workers living in Washington State after 1991, when cancer registry case accrual began, 516 first primary diagnoses occurred through 2007. While overall cancer incidence was significantly reduced [SIR: 0.83 (0.76, 0.90)], internal comparisons suggest an association with exposure comparing high to low exposed person-time [SRR: 1.28 (1.05, 1.55)]. CONCLUSION: There is evidence of styrene exposure being linked to cancer incidence, which is notable since the cohort has not yet reached the median age of cancer diagnosis (65) in the United States.

Oxidative stress biomarkers and otoacoustic emissions in humans exposed to styrene and noise.

OBJECTIVE: Evaluating the correlation between otoacoustic emission levels, styrene exposure, and oxidative stress biomarkers concentration in styrene-exposed subjects, to investigate the role of oxidative stress in outer hair cell damage. DESIGN: Distortion product otoacoustic emissions were measured in the exposed workers and in a control group. Separation between the distortion and reflection otoacoustic components was performed by time-frequency-domain filtering. The urinary concentration of the DNA and RNA oxidation products, namely 8-oxo-7,8-dihydroguanine (oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxodGuo), and 8-oxo-7,8-dihydroguanosine (oxoGuo), were evaluated. STUDY SAMPLE: Nine subjects exposed to styrene in a fiberglass factory, eight control subjects. The two groups were statistically equivalent in mean age. RESULTS: Statistically significant differences were found in the distortion component levels between the exposed and the control group. High levels of the oxidative damage biomarkers were found in the workers exposed to high levels of styrene. Significant negative correlation was found between the otoacoustic emission distortion component levels and the concentration of the oxoGuo biomarker. CONCLUSIONS: Exposure-induced damage of the cochlear amplifier is shown in the mid-frequency range, confirming animal experiments, in which hair cells in the cochlear middle turn were damaged. Hearing damage is consistent with the outer hair cell apoptosis pathway associated with oxidative stress.

Mortality among styrene-exposed workers in the reinforced plastic boatbuilding industry.

BACKGROUND: We updated mortality through 2011 for 5203 boat-building workers potentially exposed to styrene, and analysed mortality among 1678 employed a year or more between 1959 and 1978. The a priori hypotheses: excess leukaemia and lymphoma would be found. METHODS: Standardised mortality ratios (SMRs) and 95% CIs and standardised rate ratios (SRRs) used Washington State rates and a person-years analysis programme, LTAS.NET. The SRR analysis compared outcomes among tertiles of estimated cumulative potential styrene exposure. RESULTS: Overall, 598 deaths (SMR=0.96, CI 0.89 to 1.04) included excess lung (SMR=1.23, CI 0.95 to 1.56) and ovarian cancer (SMR 3.08, CI 1.00 to 7.19), and chronic obstructive pulmonary disease (COPD) (SMR=1.15, CI 0.81 to 1.58). Among 580 workers with potential high-styrene exposure, COPD mortality increased 2-fold (SMR=2.02, CI 1.08 to 3.46). CONCLUSIONS: COPD was more pronounced among those with potential high-styrene exposure. However, no outcome was related to estimated cumulative styrene exposure, and there was no change when latency was taken into account. We found no excess leukaemia or lymphoma mortality. As in most occupational cohort studies, lack of information on lifestyle factors or other employment was a substantial limitation although we excluded from the analyses those (n=3525) who worked <1 year. Unanticipated excess ovarian cancer mortality could be a chance finding. Comparing subcohorts with potential high-styrene and low-styrene exposure, COPD mortality SRR was elevated while lung cancer SRR was not, suggesting that smoking was not the only cause for excess COPD mortality.

A case of acute psychosis in a patient following exposure to a single high dose of styrene.

We report a case of acute psychotic symptoms following exposure to a single high dose of styrene monomer. The 24-year-old male patient showed psychotic and cognitive symptoms immediately after exposure. His psychotic symptoms included auditory hallucinations and delusions of reference. Brain magnetic resonance imaging, electroencephalography, and laboratory examinations were performed to evaluate any other causes. The clinical, neuroimaging, and laboratory review in this case suggested that the suddenly developed psychotic symptoms that led to chronic deterioration were caused by the single exposure to styrene monomer. This is the first recent report in which acute psychotic symptoms developed from a single high dose of styrene suffocation compared with previous findings showing symptoms because of long-term low-dose exposure.