Health & Environmental Research Online (HERO)


Trimethylbenzenes (Interagency Science Discussion Draft)

Show Project Details Hide Project Details
15 References Were Found:

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.

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.

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

Xylene-induced auditory dysfunction in humans

Authors: Fuente, A; McPherson, B; Cardemil, F (2013) Ear and Hearing 34:651-660. HERO ID: 3063454

[Less] OBJECTIVES: Animal data indicate that xylene induces cochlear dysfunction, characterized . . . [More] OBJECTIVES: Animal data indicate that xylene induces cochlear dysfunction, characterized by the loss of outer hair cells. There is little evidence regarding xylene-induced ototoxicity in humans. The aim of the study was to investigate the possible adverse effects of xylene on the peripheral and central auditory system in humans.

DESIGN: A total of 30 medical laboratory workers who had been exposed to a mixture of xylene isomers, together with 30 nonexposed control participants matched for gender, age, and educational level were selected. Participants of both groups were not exposed to noise levels above 85 dBA time-weighted average. All participants were evaluated with a comprehensive audiological test battery, which included measures of peripheral and central auditory function. Peripheral auditory measures included pure-tone audiometry and distortion product otoacoustic emissions. Behavioral measures of central auditory function included a pitch pattern sequence test, an adaptive test of temporal resolution, a dichotic digit test, and a masking level difference test. The auditory brainstem response was used to objectively evaluate the function of the auditory pathways at the brainstem level. Speech perception in quiet and in noise was evaluated using the Hearing In Noise Test (HINT). The xylene-exposed participants were extensively evaluated with regard to their exposure to both noise and xylene. Noise dosimetry was conducted over an 8-hr work shift to obtain noise-exposure levels for each xylene-exposed worker. Airborne xylene concentrations were obtained at 11 different workstations throughout the medical laboratories, and methyl hippuric acid levels per gram of creatinine in urine were obtained for each xylene-exposed subject. Finally, a detailed interview exploring current and past solvent and noise exposure was conducted.

RESULTS: The xylene-exposed participants showed significantly worse pure-tone thresholds in comparison with the nonexposed participants. The xylene-exposed participants demonstrated significantly worse results than the control group participants for the pitch pattern sequence test, dichotic digit test, HINT, and the auditory brainstem response (absolute and interpeak latencies). No significant differences between the xylene-exposed and nonexposed participants were observed for distortion product otoacoustic emissions, adaptive test of temporal resolution, or the masking level difference test. A significant correlation between the concentrations of methyl hippuric acid in urine and pure-tone thresholds (2 to 8 kHz) was found in xylene-exposed workers. Also, participants with high cumulative dose of xylene exposure presented with poorer test results than participants with low cumulative dose of xylene exposure.

CONCLUSIONS: The results of the present research suggest that xylene is associated with adverse central auditory effects and poorer sound detection abilities in humans. A major limitation of the study is that the results found among xylene-exposed participants cannot be proved to be permanent, and thus further research should be conducted to clarify this limitation. Workers exposed to this chemical should be routinely evaluated with a comprehensive audiological test battery, to detect early signs of auditory dysfunction.

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

Solid phase microextraction, mass spectrometry and metabolomic approaches for detection of potential urinary cancer biomarkers--A powerful strategy for breast cancer diagnosis

Authors: Silva, CL; Passos, M; Câmara, JS (2012) Talanta 89:360-368. HERO ID: 2871171

[Less] A sensitive assay to identify volatile organic metabolites (VOMs) as biomarkers that can accurately . . . [More] A sensitive assay to identify volatile organic metabolites (VOMs) as biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. Therefore the aim of this study was to establish the urinary metabolomic profile of breast cancer patients and healthy individuals (control group) and to explore the VOMs as potential biomarkers in breast cancer diagnosis at early stage. Solid-phase microextraction (SPME) using CAR/PDMS sorbent combined with gas chromatography-mass spectrometry was applied to obtain metabolomic information patterns of 26 breast cancer patients and 21 healthy individuals (controls). A total of seventy-nine VOMs, belonging to distinct chemical classes, were detected and identified in control and breast cancer groups. Ketones and sulfur compounds were the chemical classes with highest contribution for both groups. Results showed that excretion values of 6 VOMs among the total of 79 detected were found to be statistically different (p<0.05). A significant increase in the peak area of (-)-4-carene, 3-heptanone, 1,2,4-trimethylbenzene, 2-methoxythiophene and phenol, in VOMs of cancer patients relatively to controls was observed. Statistically significant lower abundances of dimethyl disulfide were found in cancer patients. Bioanalytical data were submitted to multivariate statistics [principal component analysis (PCA)], in order to visualize clusters of cases and to detect the VOMs that are able to differentiate cancer patients from healthy individuals. Very good discrimination within breast cancer and control groups was achieved. Nevertheless, a deep study using a larger number of patients must be carried out to confirm the results.

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

Auditory brainstem response in gas station attendants

Authors: da Silva Quevedo, L; Tochetto, T; Siqueira, MA; Machado, MS (2012) Brazilian Journal of Otorhinolaryngology 78:63-68. HERO ID: 3063459

[Less] UNLABELLED: Ototoxicity of organic solvents can affect the hearing system up to the . . . [More] UNLABELLED: Ototoxicity of organic solvents can affect the hearing system up to the cochlea level and the central structures of hearing.

OBJECTIVE: To evaluate the neurophysiological integrity of the hearing system in subjects exposed to fuels using ABR.

METHOD: Prospective study. We evaluated attendants from three gas stations in Santa Maria/RS. The sample had 21 subjects, who were evaluated by auditory brainstem response.

RESULTS: We found an alteration in the absolute latencies of Waves I and III and in all the interpeak latencies, in the right ear. In the left ear there was a change in the absolute latencies of all Waves, and in all the interpeak intervals. A change in the interaural difference of Wave V was found in 19% of the individuals. In the group exposed for more than five years, there were subjects with a statistically significant changes: in the I-V interpeak of the right ear; in the absolute latency of Wave I and in the III-V interpeak of the left year.

CONCLUSION: Exposure to fuels can cause alterations in the central hearing system.

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

Differential mRNA expression of neuroimmune markers in the hippocampus of infant mice following toluene exposure during brain developmental period

Authors: Win-Shwe, T-T; Kunugita, N; Yoshida, Y; Nakajima, D; Tsukahara, S; Fujimaki, H (2012) Journal of Applied Toxicology 32:126-134. HERO ID: 1639259

[Less] Toluene, a volatile organic compound with a wide range of industrial applications, can exert neurotoxic . . . [More] Toluene, a volatile organic compound with a wide range of industrial applications, can exert neurotoxic and immunotoxic effects. However, the effects of toluene exposure on developmental immunotoxicity in the brain have not yet been characterized. To investigate the susceptible window to toluene exposure during development and the effects of fetal and neonatal toluene exposure on the neuroimmune markers, gestational day (GD) 14 pregnant mice, postnatal day (PND) 2 and PND 8 male offspring were exposed to filtered air (control; 0 ppm), or 5 or 50 ppm toluene for 6 h per day for five consecutive days. The neuroimmune markers in the hippocampus of PND 21 were examined using a real-time RT-PCR and immunohistochemical analysis. Mice exposed to 50 ppm toluene on PND 2-6 showed significantly increased levels of nerve growth factor (NGF) and tumor necrosis factor (TNF)-α mRNAs. In contrast, NGF and brain-derived neurotrophic factor (BDNF) and proinflammatory cytokines TNF-α, CCL3, NF-κB, toll-like receptor (TLR)-4, astrocyte marker glial fibrillary acidic protein (GFAP), and microglia marker ionized calcium binding adapter molecule (Iba)-1 mRNAs were increased significantly in mice exposed to 5 ppm toluene on PND 8-12. These results indicate that low-level toluene exposure during the late postnatal period (PND 8-12) might induce neuroinflammatory mediators via TLR4-dependent NF-κB pathway in the hippocampus of PND 21 male mice. Among the three developmental phases, PND 8-12 seems to be most sensitive to toluene exposure. This is the first study to show developmental phase- and dose-specific changes in neuroimmune markers in infant mice following toluene exposure.

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

Occupational solvent exposure and brain function: An fMRI study

Authors: Tang, CY; Carpenter, DM; Eaves, EL; Ng, J; Ganeshalingam, N; Weisel, C; Qian, H; Lange, G; Fiedler, NL (2011) Environmental Health Perspectives 119:908-913. HERO ID: 3063461

[Less] BACKGROUND: Deficits in cognitive function have been demonstrated among workers chronically . . . [More] BACKGROUND: Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown.

OBJECTIVES: We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers.

METHODS: Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure.

RESULTS: Solvent-exposed workers' performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices--areas serving working memory function and attention--was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers.

CONCLUSIONS: This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology caused by prolonged exposure to solvent mixtures during construction work.

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

Investigation of urinary volatile organic metabolites as potential cancer biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry

Authors: Silva, CL; Passos, M; Câmara, JS (2011) British Journal of Cancer 105:1894-1904. HERO ID: 1488570

[Less] BACKGROUND: Non-invasive diagnostic strategies aimed at identifying biomarkers of cancer . . . [More] BACKGROUND: Non-invasive diagnostic strategies aimed at identifying biomarkers of cancer are of great interest for early cancer detection. Urine is potentially a rich source of volatile organic metabolites (VOMs) that can be used as potential cancer biomarkers. Our aim was to develop a generally reliable, rapid, sensitive, and robust analytical method for screening large numbers of urine samples, resulting in a broad spectrum of native VOMs, as a tool to evaluate the potential of these metabolites in the early diagnosis of cancer.

METHODS: To investigate urinary volatile metabolites as potential cancer biomarkers, urine samples from 33 cancer patients (oncological group: 14 leukaemia, 12 colorectal and 7 lymphoma) and 21 healthy (control group, cancer-free) individuals were qualitatively and quantitatively analysed. Dynamic solid-phase microextraction in headspace mode (dHS-SPME) using a carboxen-polydimethylsiloxane (CAR/PDMS) sorbent in combination with GC-qMS-based metabolomics was applied to isolate and identify the volatile metabolites. This method provides a potential non-invasive method for early cancer diagnosis as a first approach. To fulfil this objective, three important dHS-SPME experimental parameters that influence extraction efficiency (fibre coating, extraction time and temperature of sampling) were optimised using a univariate optimisation design. The highest extraction efficiency was obtained when sampling was performed at 50°C for 60 min using samples with high ionic strengths (17% sodium chloride, w v(-1)) and under agitation.

RESULTS: A total of 82 volatile metabolites belonging to distinct chemical classes were identified in the control and oncological groups. Benzene derivatives, terpenoids and phenols were the most common classes for the oncological group, whereas ketones and sulphur compounds were the main classes that were isolated from the urine headspace of healthy subjects. The results demonstrate that compound concentrations were dramatically different between cancer patients and healthy volunteers. The positive rates of 16 patients among the 82 identified were found to be statistically different (P<0.05). A significant increase in the peak area of 2-methyl-3-phenyl-2-propenal, p-cymene, anisole, 4-methyl-phenol and 1,2-dihydro-1,1,6-trimethyl-naphthalene in cancer patients was observed. On average, statistically significant lower abundances of dimethyl disulphide were found in cancer patients.

CONCLUSIONS: Gas chromatographic peak areas were submitted to multivariate analysis (principal component analysis and supervised linear discriminant analysis) to visualise clusters within cases and to detect the volatile metabolites that are able to differentiate cancer patients from healthy individuals. Very good discrimination within cancer groups and between cancer and control groups was achieved.

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

Does early life toluene exposure alter the expression of NMDA receptor subunits and signal transduction pathway in infant mouse hippocampus?

Authors: Win-Shwe, T-T; Yoshida, Y; Kunugita, N; Tsukahara, S; Fujimaki, H (2010) NeuroToxicology 31:647-653. HERO ID: 3063462

[Less] We aim to investigate the critical window of susceptibility to toluene exposure during brain development . . . [More] We aim to investigate the critical window of susceptibility to toluene exposure during brain development and the effects of fetal and neonatal toluene exposure on the expression of N-methyl-d-aspartate (NMDA) receptor subunits and related transduction pathway in infant mice hippocampus. Pregnant mice (GD 14), male offspring (postnatal day; PND 2) or PND 8 were exposed to either a filtered air control (0ppm), or 5, or 50ppm of toluene for 6h per day for 5 consecutive days. On PND 21, the expression levels of NMDA receptor subunits, cyclic AMP responsive element binding protein (CREB)-1, calcium/calmodulin-dependent protein kinase (CaMK)-IV, and apoptotic related genes (Bax, Bcl) mRNAs in the hippocampus were estimated using quantitative real-time RT-PCR and immunohistochemical analyses. NR2B, CaMKIV and CREB1 mRNAs increased significantly in the hippocampus of mice exposed to 50ppm toluene on PND 2-6. In contrast, almost all memory function-related gene mRNAs and proapoptotic and anti-apoptotic ratio increased significantly in mice exposed to 5 or 50ppm toluene on PND 8-12. However, mice exposed to toluene on GD 14-18 showed no significant change. Increased active caspase-3 immunoreactive cells were found in hippocampal CA1 area of PND 21 male mice exposed to 5ppm toluene during PND 8-12. Our results suggest that late postnatal period may be a vulnerable and critical period to toluene exposure. Then, we have also examined the effect of toluene exposure in brain development on learning ability in young adult mice and found that poor spatial learning performance in PND 49 male mice exposed to 5ppm toluene during critical period. This is the first study to show that the early toluene exposure induces persistent of the alteration of memory function-related genes in infant mice and memory deficit in later life via modulating the synaptic morphology and function.

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

Modeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: A case study with toluene

Authors: Nong, A; McCarver, DG; Hines, RN; Krishnan, K (2006) Toxicology and Applied Pharmacology 214:78-87. HERO ID: 818602

[Less] The objective of the present study was to evaluate the magnitude of interindividual variability in the . . . [More] The objective of the present study was to evaluate the magnitude of interindividual variability in the internal dose of toluene in children of various age groups, on the basis of subject-specific hepatic CYP2E1 content and physiology. The methodology involved the use of a previously validated physiologically based pharmacokinetic (PBPK) model, in which the intrinsic clearance for hepatic metabolism (CL(int)) was expressed in terms of the CYP2E1 content. The adult toluene PBPK model, with enzyme content-normalized CL(int), facilitated the calculation of child-specific CL(int) based on knowledge of hepatic CYP2E1 protein levels. The child-specific physiological parameters, except liver volume, were computed with knowledge of age and body weight, whereas physicochemical parameters for toluene were kept age-invariant based on available data. The actual individual-specific liver volume (autopsy data) was also included in the model. The resulting model was used to simulate the blood concentration profiles in children exposed by inhalation, to 1 ppm toluene for 24 h. For this exposure scenario, the area under the venous blood concentration vs. time curve (AUC) ranged from 0.30 to 1.01 microg/ml x h in neonates with low CYP2E1 concentration (<3.69 pmol/mg protein). The simulations indicated that neonates with higher levels of CYP2E1 (4.33 to 55.93 pmol/mg protein) as well as older children would have lower AUC (0.16 to 0.43 microg/ml x h). The latter values were closer to those simulated for adults. Similar results were also obtained for 7 h exposure to 17 ppm toluene, a scenario previously evaluated in human volunteers. The interindividual variability factor for each subgroup of children and adults, calculated as the ratio of the 95th and 50th percentile values of AUC, was within a factor of 2. The 95th percentile value of the low metabolizing neonate group, however, was greater than the mean adult AUC by a factor of 3.9. This study demonstrates the feasibility of incorporating subject-specific data on hepatic CYP2E1 content and physiology within PBPK models for evaluating the age, interchild and population variability of internal dose for use in risk assessment of inhaled volatile organics.