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Trimethylbenzenes (Interagency Science Discussion Draft)

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Data/Software
Data/ Software

Results of the BMD analyses for 1,2,4-TMB, 1,2,3-TMB, and 1,3,5-TMB

Author: U.S. EPA (2016) HERO ID: 3103169

[Less] : This zipfile contains all input files (.dax files), analysis files (.opt, .ssn, .(d), and .002 files), . . . [More] : This zipfile contains all input files (.dax files), analysis files (.opt, .ssn, .(d), and .002 files), and output files (.out, .emf, and .plt files) used in and generated by the BMD analyses on endpoints considered for the derivation of reference values for 1,2,4-TMB, 123, and 1,3,5-TMB in the Interagency Science Discussion draft of the Toxicological Review for Trimethylbenzenes. This zipfile also contains all BMDS Wizard files (macro enabled Excel workbooks, .xlsm) that were used in the BMD modeling analyses. These BMDS Wizard files store within them all the modeling results for an individual endpoint, and can be used to interpret these endpoint-specific results holistically, rather than inspecting model-specific .out and .plt files. Lastly, this zipfile contains a modeling report (.docx) for each modeling analysis; these reports were used to create the BMD Modeling appendix (Appendix D) in the Supplemental Information Document for Trimethylbenzenes.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Hemimellitene (1,2,3-trimethylbenzene) in the liver, lung, kidney, and blood, and dimethylbenzoic acid isomers in the liver, lung, kidney and urine of rats after single and repeated inhalation exposure to hemimellitene

Authors: Świercz, R; Majcherek, W; Wąsowicz, W (2016) International Journal of Occupational Medicine and Environmental Health 29:113-128. HERO ID: 3044616

[Less] OBJECTIVES: The aim of the study has been to explore hemimellitene distribution in blood, liver, lung . . . [More] OBJECTIVES: The aim of the study has been to explore hemimellitene distribution in blood, liver, lung and kidney as well as toxicokinetics of its elimination from blood of rats after single and repeated inhalation exposure to this compound. Tissue distribution and excretion with urine of 2-dimethylbenzoic acids (2,3-DMBA and 2,6-DMBA) were also evaluated.

MATERIAL AND METHODS: Male outbred IMP:WIST rats were used in the experiment. The animals were exposed to hemimellitene vapors at the nominal concentration of 25 ppm, 100 ppm, and 250 ppm in the dynamic inhalation chambers for 6 h for single exposure purpose and for 4 weeks (6 h/day for 5 day/week) for repeated exposure purposes.

RESULTS: Significantly lower concentrations of hemimellitene were detected in the blood and tissues of animals after repeated inhalation exposure of animals to hemimellitene vapors, which points to reduced retention of the chemical in the lungs of the experimental rats. The trend of hemimellitene elimination from the blood depended solely on exposure intensity, irrespective of exposure time, both after single and repeated exposure. As regards the 2 determined hemimellitene metabolites, the major trend of the metabolic transformation involved formation of 2,3-DMBA.

CONCLUSIONS: The significantly higher urinary 2,3-DMBA concentration after repeated exposure shows that hemimellitene induces enzymatic processes in the rat.

Data/Software
Data/ Software

PBPK data files for TMB (updated February 2016)

Author: U.S. EPA (2016) [Data files]. Research Triangle Park, NC: U.S. Environmental Protection Agency. [PBPK] HERO ID: 3103168

[Less] This model code package contains the PBPK files used in the testing and validation of the PBPK model . . . [More] This model code package contains the PBPK files used in the testing and validation of the PBPK model used in the Toxicological Review for Trimethylbenzenes, as well the files used in the PBPK extrapolations of inhalation data for the purpose of deriving reference concentrations, and the route-to-route extrapolation of inhalation data to oral exposures for the purpose of deriving reference doses.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The sub-chronic toxicity of regular White Spirit in rats

Authors: Carrillo, J-C; Adenuga, MD; Mckee, RH (2014) Regulatory Toxicology and Pharmacology 70:222-230. HERO ID: 2897466

[Less] Hydrocarbon solvents are mostly complex substances (UVCB) with carbon numbers in the range of approximately . . . [More] Hydrocarbon solvents are mostly complex substances (UVCB) with carbon numbers in the range of approximately C5-C20. One of the most common types is a C9-C14 aliphatic solvent containing approximately 20% aromatics and commonly known as White Spirit in Europe and mineral spirits in the US. In previous repeated inhalation toxicity studies, White Spirit was reported to cause minimal systemic effects in most animal species with few effects other than male rat-specific kidney changes at levels up to approximately 2000mg/m(3). In the present study male and female rats were exposed to White Spirit vapors, 6h/day, 5days/week for 13weeks at levels of approximately 2000, 4000, or 8000mg/m(3) to assess the potential for effects at higher exposure levels. All of the rats survived the treatment period. In life observations were largely restricted to acute central nervous system (CNS) effects in the high exposure group. Terminal body weights of high exposure groups animals were significantly below control values. Statistically significant differences in the clinical and hematological observations were small and within normal physiological limits. Weights of some organs including liver, spleen and kidneys were elevated, but microscopic examination indicated that the only pathological effects were changes in the kidneys of the male rats, consistent with an α2u-globulin-mediated process, which is gender and species-specific and not relevant to humans. The overall no observed adverse effect level (NOAEC) was 4000mg/m(3).

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Neurobehavioral performance in volunteers after inhalation of white spirits with high and low aromatic content

Authors: Juran, SA; Johanson, G; Ernstgård, L; Iregren, A; van Thriel, C (2014) Archives of Toxicology 88:1127-1140. HERO ID: 3044623

[Less] The content of aromatic hydrocarbons in solvent mixtures, such as white spirits (WS), has been assumed . . . [More] The content of aromatic hydrocarbons in solvent mixtures, such as white spirits (WS), has been assumed a major contributor to the neurotoxic effects of these compounds. Hence, dearomatized WS have been introduced to the market rapidly in the last decade. Studies investigating other aromatic hydrocarbons (toluene) and animal models have supported the aforementioned assumption, but the current study is the first one to compare acute neurobehavioral effects of exposure to aromatic and dearomatized WS (aWS, daWS) content in human volunteers at current occupational exposure limit values. In a pseudo-randomized crossover design, six female and six male healthy volunteers were exposed to aWS and daWS at two concentrations (100 and 300 mg/m(3)) and to clean air for 4 h at rest. During each of the five exposure conditions, volunteers performed five neurobehavioral tasks that were selected following a multidisciplinary approach that accounted for findings from the cognitive neurosciences and mechanisms of solvent toxicity. Two of the tasks indicated performance changes during aromatic WS exposure, the working memory (WM) and the response shifting task, but both effects are difficult to interpret due to low mean accuracy in the WM task and due to a lack of dose-response relationship in the response shifting task. Healthy human volunteers showed weak and inconsistent neurobehavioral impairment after 4-h exposures to 100 and 300 mg/m(3) aromatic or dearomatized WS. Our multidisciplinary approach of selecting neurobehavioral test methods may guide the test selection strategies in future studies.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The sub-chronic oral toxicity of 1,3,5-trimethylbenzene in Sprague-Dawley rats

Authors: Adenuga, D; Carrillo, JC; Mckee, RH (2014) Regulatory Toxicology and Pharmacology 69:143-153. HERO ID: 2899217

[Less] The systemic toxicity of a trimethylbenzene isomer and constituent of C9 aromatic solvents (1,3,5-trimethylbenzene, . . . [More] The systemic toxicity of a trimethylbenzene isomer and constituent of C9 aromatic solvents (1,3,5-trimethylbenzene, 135-TMB) was studied in Sprague-Dawley rats following a 90-day oral gavage exposure to 0, 50, 200 and 600 mg/kg/day. No statistically significant effects on body weight, body weight gain or food consumption were observed at study termination. Treatment-related changes in clinical chemistry parameters at the end of the 90-day dosing period were limited to small, but statistically significant, increases in phosphorus levels in high dose males and females. Liver enlargement in high dose male/female rats was considered an adaptive response as this was reversible and was not associated with histopathological lesions or increased liver enzyme markers indicative of liver damage. Kidney weight changes were limited to a small, but statistically significant, increase in relative weights in high dose males. This was not associated with histopathological lesions and thus not considered toxicologically relevant. Overall, the No-Observed-Adverse-Effect-Level (NOAEL) was the highest concentration tested (600 mg/kg/day). The results of the present study are relevant for assessing the risk of trimethylbenzenes through the oral route of exposure and provide a basis for the development of provisional screening values for trimethylbenzene isomers while avoiding the uncertainty associated with route-to-route extrapolation.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Ototoxicity effects of low exposure to solvent mixture among paint manufacturing workers

Authors: Juárez-Pérez, CA; Torres-Valenzuela, A; Haro-García, LC; Borja-Aburto, VH; Aguilar-Madrid, G (2014) International Journal of Audiology 53:370-376. HERO ID: 3063457

[Less] OBJECTIVE: To evaluate auditory function in a group of workers exposed to organic solvent . . . [More] OBJECTIVE: To evaluate auditory function in a group of workers exposed to organic solvent mixture at a paint factory.

DESIGN: Cross-sectional study.

STUDY SAMPLE: One hundred and sixty-one workers were studied, 77 exposed to solvents and 84 unexposed. Fourteen solvents were measured, including toluene, xylene, and n-hexane. Pure-tone audiometry and brainstem auditory-evoked potentials (BAEP) were performed. Industrial noise was < 85 dBA and exposure levels to organic solvents were low.

RESULTS: The exposed group showed a hearing impairment in both ears compared with the unexposed workers. Multiple linear regression models adjusted by age, chronic pathologies, and environmental noise for frequency means between 125 and 8000 Hz produced the following results: for the left ear, R(2) = 33.3%, exposed vs. unexposed β = 4.1 (p < 0.001); and for the right ear, R(2) = 38%, exposed vs. unexposed β = 4.8 (p < 0.001). Adjusted for age and chronic pathologies, waves III and V, and interpeak interval latencies were increased (p < 0.05) in both ears in the exposed group.

CONCLUSIONS: Although solvent mixture concentrations and noise levels were low, our results demonstrate that there may be a concurrent ototoxicity and neurotoxicity condition and emphasize the importance of including BAEP analysis for comprehensive assessments. Future studies that include otoacoustic emissions assessments to monitor cochlear function and central auditory processing tests are imperative.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Postural sway and exposure to jet propulsion fuel 8 among US Air Force personnel

Authors: Maule, AL; Heaton, KJ; Rodrigues, E; Smith, KW; McClean, MD; Proctor, SP (2013) Journal of Occupational and Environmental Medicine 55:446-453. HERO ID: 2893964

[Less] OBJECTIVE: To determine whether short-term jet propulsion fuel 8 (JP-8) exposure is . . . [More] OBJECTIVE: To determine whether short-term jet propulsion fuel 8 (JP-8) exposure is associated with balance measurements in JP-8-exposed air force personnel.

METHODS: As part of a larger neuroepidemiology study, balance tasks were completed by JP-8-exposed individuals (n = 37). Short-term JP-8 exposure was measured using personal breathing zone levels and urinary biomarkers. Multivariate linear regression analyses were conducted to examine the relationship between workday JP-8 exposure and postural sway.

RESULTS: Balance control decreased as the task became more challenging. Workday exposure to JP-8, measured by either personal air or urinary metabolite levels, was not significantly related to postural sway. Increases in workday postural sway were associated with demographic variables, including younger age, being a current smoker, and higher body mass index.

CONCLUSION: Results suggest that short-term workday JP-8 exposure does not significantly contribute to diminished balance control.

Book/Book Chapter
Book/ Chapter

Acute exposure guideline levels for selected airborne chemicals

Author: NRC (2013) Washington, DC: National Academies Press. HERO ID: 3063435

[Less] At the request of the Department of Defense and the Environmental Protection Agency, the National Research . . . [More] At the request of the Department of Defense and the Environmental Protection Agency, the National Research Council has reviewed the relevant scientific literature compiled by an expert panel and established Acute Exposure Guideline Levels (AEGLs) for several chemicals. AEGLs represent exposure levels below which adverse health effects are not likely to occur and are useful in responding to emergencies, such as accidental or intentional chemical releases in community, workplace, transportation, and military settings, and for the remediation of contaminated sites.

Three AEGLs are approved for each chemical, representing exposure levels that result in: 1) notable but reversible discomfort; 2) long-lasting health effects; and 3) life-threatening health impacts. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13 includes AEGLs for boron trifluoride, bromoacetone, chloroacetone, hexafluoroacetone, perchloryl fluoride, piperidine, propargyl alcohol, trimethoxysilane and tetramethoxysilane, and trimethylbenzenes.

Journal Article
Journal Article

Health hazards of solvents exposure among workers in paint industry

Authors: El Hamid Hassan, AA; El Moez Elnagar, SA; El Tayeb, IM; El Halim Bolbol, SA (2013) Open Journal of Safety Science and Technology 3:87-95. HERO ID: 3063436

[Less] Background: Paints and coatings include paints, varnishes, lacquers, stains, printing inks and more. . . . [More] Background: Paints and coatings include paints, varnishes, lacquers, stains, printing inks and more. A wide variety of volatile solvents are used in paint and coating manufacturing including aliphatic and aromatic hydrocarbons, alcohols, ketones and consist of more than 30% of most of paints. At low or moderate concentrations, the organic solvents may cause transient symptoms such as euphoria, headache and dizziness. At high concentrations, anaesthesia and disturbances in respiration and circulation may occur and may lead to death. Long-term exposure may cause damage to the Central Nervous System (CNS), such as cognitive and emotional deficits.

Methods: A cross sectional study was conducted among 92 male workers exposed to organic solvents on performing their job in Koratol Paint Factory in Alaama Village in Sharkia Governorate. Another group of 95 workers, not working with organic solvents were selected from the Faculty of Medicine in Zagazig University and considered as a control group. All participants in the study were subjected to a pre-designed questionnaire to collect information about personal, socio-demographic data, occupational history, use of personal protective equipments, frequently perceived health complaints which included irritation symptoms (skin, eye and nose) and Questions of the validated questionnaire for the neuropsychological symptoms (Q22).

Results: The neuropsychological symptoms score (Q22) revealed that 63.04% of solvents exposed paint manufacturing workers had neuropsychological symptoms, compared to about only 2.1% in control group and the difference was statistically significant. Regarding the relation between types of job done and results of neuropsychological symptoms score (Q22) there was increased risk for neuropsychological symptoms in production group than packing group (OR = 13.94) and for the duration of work the risk increased in workers with duration over 15 years (OR = 32.84). Logistic regression analysis showed that the most important predictors of neuropsychological symptoms were the type of job performed by the workers such as production or packing and their duration of work ≥15 years.

Conclusions: The paint industry workers were at increased risk of several irritant and neuropsychological symptoms which significantly related to exposure to paint and organic solvents.