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Efectos para la Salud

Efectos en la salud

Exposición a Hidrocarburos Aromáticos

George L. Delclós, M.D., M.P.H.1, Sarah A. Felknor, Dr.P.H., M.S. 1, María T. Morandi, Ph.D., C.I.H. 1, Arch I. Carson, M.D., Ph.D. 1, Keith D. Burau, Ph.D. 1, Edilma Guevara, R.N., Dr.P.H.2 and Katherine A. Murray, M.S. 3

1Southwest Center for Occupational and Environmental Health
University of Texas - Houston Health Science Center
School of Public Health
Houston, Texas

2School of Nursing
University of Texas Medical Branch
Galveston, Texas

3Eagle Environmental, Inc.
Houston, Texas


The Barrancabermeja Industrial Complex (CIB) is a large refinery that since 1970 has housed various plants with a potential for exposure to benzene, toluene and xylenes (BTX). The CIB has recognized the need to gain insight into the current health status of its workers, with the ultimate objectives of defining specific interventions and developing an infrastructure that will provide a system of primary prevention and surveillance of personnel in these and other plants with potential chemical exposures.

Because of this need, the national oil company of Colombia (ECOPETROL) and its union (USO) created a joint labor-management Aromatics Commission that agreed to oversee the conduct of a series of independent scientific research projects to evaluate the individual and collective health status of its workers, and to develop recommendations based on these findings. This large "Occupational Health in the Petroleum Industry Project" (SOIP) was created under an Agreement signed by the Government of Colombia, ECOPETROL and the World Health Organization/Pan American Health Organization, and initially consisted of several components: Epidemiology, Occupational Medicine, General Laboratory and Toxicology, Sociology and Work Environment (Industrial Hygiene and Ergonomics).

This chapter describes those studies corresponding to the Occupational Medicine, General Laboratory and Toxicology components of the SOIP, which were conducted by a research team from the University of Texas-Houston Health Science Center School of Public Health, through its Southwest Center for Occupational and Environmental Health (SWCOEH). Collectively, these studies are known as the "Cross-sectional study of workers with potential exposure to aromatic hydrocarbons".




The primary objectives of this cross-sectional study were to:
1. identify possible adverse health effects among potentially BTX-exposed workers, and to establish a baseline health profile of these workers that would be useful in future studies;
2. determine the prevalence and severity of these possible adverse health effects in this group of workers;
3. evaluate possible associations between workplace variables and adverse health effects (notwithstanding the limitations of cross-sectional studies);
4. provide orientation for those workers in whom possible adverse health effects were detected towards appropriate medical follow-up;
5. prepare recommendations conducive to the early detection of disease, promotion of health and epidemiological surveillance in this group of workers.

Study Design

This was designed as a cross-sectional study of workers with potential aromatic hydrocarbon exposure. This design was selected for several reasons:
1. cross-sectional studies are quick and relatively simple to conduct;
2. given the diversity of possible exposures and of potential health effects, this type of study allows an initial evaluation of multiple exposure(s) and disease(s) at a single point in time; from this evaluation, one or various hypotheses can be generated for future studies that are amenable to more powerful study designs;
3. results of a cross-sectional study, although they do not establish causal relationships between exposure and adverse health effects, can be consistent with previously established cause-effect relationships.

Study Population

The target population was defined as all current workers with a potential for exposure to aromatic hydrocarbons at the Barrancabermeja Industrial Complex, as well as a limited sample of retirees. This target population was identified from employee lists, previously developed by the Aromatics Commission and delivered to PAHO-Bogotá and the University of Texas research team. Current workers were identified from payroll lists that existed as of December 31, 1995.

The final sample size of the study population was set at approximately 730 workers, at a meeting of the Aromatics Commission, Colombian Ministry of Health and PAHO/WHO-Bogotá, held on September 9 and 10, 1995 in Bogota. The final study population was composed of the following groups:
1. an exhaustive sample of all current workers in the Aromatics/Alkyls unit, Paraffins unit, External Elements unit and Quality Control Laboratory.
2. a representative random sample of maintenance workers with potential aromatic hydrocarbon exposure. In an initial health hazard evaluation conducted by a team from the U.S. National Institute for Occupational Safety and Health (NIOSH) in May 1994, maintenance workers had been identified as the group with the greatest potential for exposure to BTX, based on a limited number of personal exposure measurements. Consequently, inclusion of this group in the study was considered to be essential. However, given the large number of maintenance workers, and the pre-set maximum study size of 730 persons, the research team opted for obtaining a representative random sample of at least 234 (i.e., >15% of all workers in the maintenance area) of this group of employees.
3. a convenience sample of retirees who had worked in any of these same areas. The union representatives on the Aromatics Commission felt that it would be important to include a sample of retirees and transferred workers; this was agreed to in meetings that preceded the final approval of the study protocol. However, since the denominator (target population) of retirees was unknown, obtaining a representative random sample was not felt to be feasible. Instead, a convenience sample was obtained.

To maximize worker participation in this study, written information on the study was distributed to each worker before the field phase. This information was distributed using the usual channels available to both the union and the company. In addition, meetings were held with the target population in Barrancabermeja, approximately two weeks before starting the field phase. At each of these meetings there were representatives of the Aromatics Commission, Ministry of Health, PAHO/WHO and the team from the University of Texas. During the meetings, an explanation of the various study components was given, worker questions were answered, study subject rights and responsibilities were reviewed, and maximum participation was requested. In agreement with the Aromatics Commission, no worker selected for the study was scheduled for vacation time during the field phase.

Study Components

Each study participant completed a previously developed and pilot-tested interviewer-administered questionnaire that focused on an occupational, environmental and medical history. Each participant also underwent a directed physical examination, focused on anthropometric measurements (height and weight), vital signs (arterial blood pressure and heart rate), a complete skin examination by a dermatologist, and a cardiopulmonary examination. Likewise, each participant performed a pulmonary function test (spirometry) and underwent posteroanterior chest radiography and analysis of blood and urine specimens for the determination of a complete blood cell count, serum chemistry profile (SMA-20), measurement of blood benzene, toluene and total xylenes, and measurement of urinary metabolites of benzene (phenol, trans-transmuconic acid, hydroquinone and cathecol) and toluene (hippuric acid).

In addition, a subgroup of 33 workers, representing each work area, underwent personal sampling and area monitoring to quantitatively estimate exposure to aromatic hydrocarbons, and measurement of additional urinary metabolites of toluene (ortho-cresol) and xylene (methylhippuric acid). The main objective of this industrial hygiene component was to evaluate the correlation between environmental exposure levels and blood/urine concentrations of BTX metabolites, as well as to identify exposures to other organic compounds that might be present at significant levels in the workplace. During this industrial hygiene study, the availability and quality of employment records present at the CIB were reviewed, in order to determine the feasibility of conducting a reliable retrospective exposure assessment and/or occupational cohort studies in the future.

Data Analysis

Data collection, database management and statistical analyses were conducted at the University of Texas School of Public Health. All data were entered into a FoxPro Version 2.0 database. Statistical analysis was performed using SPSS (Statistical Package for the Social Sciences, Version 7.0 for Windows).

Study Variables

In this initial analysis, occupational exposures were defined on the basis of years of employment at ECOPETROL, job title, plant area, and/or exposure or involvement in an accidental release or spill of a chemical, BTX blood levels and BTX metabolites in urine. Demographic variables included age, height, ethnicity and Fitzpatrick skin type. Personal lifestyle habits centered on tobacco use and alcohol consumption. Collectively, these groups of variables are referred to as the independent variables.

Based on what is known in the scientific literature concerning adverse health effects of aromatic hydrocarbon exposure, the following dependent variables were evaluated in this first analysis:

Respiratory system: prior diagnoses of frequent respiratory infections, asthma and sinusitis/rhinitis; symptoms of chronic bronchitis, wheezing and shortness of breath. Spirometric lung function: forced vital capacity (FVC), forced expired volume in the first second (FEV1), FEV1/FVC and mid-expiratory flows (FEF 25%-75%). These physiological variables were analyzed as absolute values and as a percent of predicted values (Crapo, 1981; ATS, 1991). Chest radiographs, interpreted using the 1980 International Labour Office Classification of Radiographs of the Pneumoconioses, which allows the coding of parenchymal and pleural changes. The main radiographic variables studied included film quality, presence or absence of parenchymal abnormalities, profusion grade, presence or absence of pleural abnormalities, type of pleural abnormality (circumscribed or diffuse), and presence or absence of pleural calcifications. The final profusion grade was defined as the median of three independent readings. The presence or absence of pleural abnormalities was defined by the majority reading among the three readers.

Skin: two dermatology-related variables were analyzed. The first, "contact dermatitis", was defined as skin changes in one or both hands (dorsum and/or palm) and/or forearms (anterior and/or posterior surface) that were classified by a dermatologist as being possibly compatible with a contact dermatitis. The second variable, "athlete's foot", was defined as lesions compatible with tinea pedis, involving one or both feet.

Liver function: liver function abnormality was defined as an abnormal elevation of at least two of the following serum liver function studies: ALT (SGOT), AST (SGPT), GGTP, total bilirubin, alkaline phosphatase and/or LDH.

Hematopoietic system: abnormalities of the complete blood cell count (hemoglobin, hematocrit, red blood cell indices, white blood cell count and differential, platelet count).

Data Quality

To evaluate the representativeness of the random sample of maintenance workers, the sample population distribution of job titles was compared to that of the target population of maintenance workers. To assess questionnaire completeness, the number of completed questionnaires was obtained and internal validity of the data was calculated in a 10% sample of questionnaires. For spirometry, the number of tests that did not fulfill ATS validity (acceptability) criteria and/or reproducibility was computed. For chest radiographs, the percent of radiographs not deemed to be quality 1 films (i.e., those rated 2, 3 or unreadable, according to the ILO scale) was calculated. For blood and urine assays, blank samples, spiked samples and duplicate samples (for approximately 10% of all study subjects) were analyzed as external controls, in addition to the routine internal controls conducted by each laboratory. For quality assurance purposes, an independent observer, contracted by PAHO, provided external verification of all testing conducted during the field phase.

Final Study Population for Analysis

Two populations were defined for analysis, based on the original study population definition and initial descriptive statistics. First, study subjects with incomplete data were excluded from the final analysis. Next, due to the small number of women in this population (n=8), the final analysis was limited to male participants. Finally, since retirees were based on a convenience sample, whereas the remainder of the study population formed a representative sample of their target populations, the remaining study subjects were divided into two groups, current workers and retirees, which were separately analyzed.

Descriptive Statistics

For continuous variables, measures of central tendency were calculated; for categorical or dichotomous variables, frequency histograms were plotted. Prevalence of each independent and dependent variable was calculated.

Univariate Analysis

Following the descriptive statistics, associations between independent and dependent variables were evaluated using the crude odds ratio (O.R.) to measure strength of the association. Statistical significance (precision) of these estimates was measured using Cornfield or Exact 95% confidence intervals, depending on the size of each cell. Reference groups (i.e., non-exposed or least exposed) were initially defined based on the preliminary results obtained during the 1994 NIOSH Health Hazard Evaluation, the shortest duration of employment and/or knowledge of the natural history of a specific adverse health outcome. For continuous variables, differences in measures of central tendency among groups were calculated using an analysis of variance.

Stratified Analysis

The associations between independent and dependent variables were further evaluated, while controlling for the effect of possible confounding variables, using stratified analysis. Possible confounders were identified based on the results of the univariate analysis and/or biological plausibility. Strength of the association was measured by the adjusted Mantel-Haenszel O.R. Statistical significance (precision) of the association was measured using 95% confidence intervals.

Multivariate Analysis

Based on statistically significant associations identified through the univariate and/or stratified analyses, multivariate analysis was performed using a logistic regression model, with calculation of the corresponding O.R. and 95% confidence intervals.

Ethical Review

This cross-sectional study was conducted with strict adherence to the Code of Ethics adopted by the 18th World Medical Assembly in 1964 (Helsinki Declaration), and subsequently revised in 1981. All study subjects were previously informed on the details of their participation through printed brochures, worker meetings and small group meetings (6 to 15 persons) with the principal investigator, before giving their written informed consent. During the field phase of the study, USO and Aromatics Commission representatives were present to facilitate the conduct of the study. The study protocol was approved by the University of Texas-Houston Committee for the Protection of Human Subjects, the Colombian Ministry of Health and the PAHO/WHO Ethics Committee.


Individual Results

Once the study data were compiled, individual reports were prepared for each study participant, containing results of the physical examination, pulmonary function test, chest radiography, complete blood cell count and SMA-20. These confidential reports were given by the research team to the workers during a series of employee meetings held at the Barrancabermeja complex in June 1996, at which the interpretation of the reports was explained, information on health promotion and healthy lifestyles was provided, and questions were answered. Following this, the research team met individually with study participants with abnormal results, offered recommendations for follow-up and also offered to make the results available to their personal physicians.

Group Results

In all, 733 workers were evaluated during the field phase of the study. Of these, 3 participants were excluded because they did not meet the target population definition. Another 5 participants were excluded because of incomplete data. The 8 women (<1% of the total study population) were also excluded from final analysis. Aggregate data were analyzed for a final study population of 717 male participants (610 current workers and 107 retirees). Based on the high level of study participation (close to 100% of the initial study sample), completeness of the data and internal validity of the data, we believe the quality of information obtained and the subsequent database that has been generated to be reliable. Demographic and occupational profiles of the study population are summarized in Table 1.

In the descriptive analysis of possible adverse health outcomes (Table 2), strikingly high prevalences were identified for being overweight (current workers - 75%; retirees - 77%); elevated arterial blood pressure (current workers - 25%; retirees - 53%); frequent respiratory infections (current workers - 24%; retirees - 31%); sinusitis/rhinitis (current workers - 10%); chronic bronchitis (current workers - 18%; retirees - 22%); dyspnea (current workers - 14%; retirees - 21%); possible contact dermatitis involving the upper extremities (current workers - 4%); athlete's foot (current workers - 37%; retirees - 41%); hypercolesterolemia (current workers - 53%; retirees - 66%); hypertriglyceridemia (current workers - 38%; retirees - 43%) and elevation of at least two tests of liver function (current workers - 11%; retirees - 11%).

Tables 3A-3D and 4A-4C summarize the univariate and stratified analysis results, respectively. With respect to respiratory abnormalities in current workers, controlled for the effect of smoking through stratified analysis, significant associations were found between years of employment at ECOPETROL and dyspnea (O.R. - 1.65; 95%CI - 1.05 to 2.60) and between exposure to a significant spill or accidental chemical release at work and chronic bronchitis (O.R. - 1.73; 95%CI - 1.14 to 2.63).

Based on results from the stratified analysis, the association between years of employment at ECOPETROL and prevalence of dyspnea was further examined through logistic regression. With dyspnea as the dependent variable, the following confounders were included in the final model: pack-years of smoking age, being overweight and a past history of heart disease. The resulting saturated model (p=0.004) revealed the following associations:

Independent variable O.R. 95%CI p value
Years at ECOPETROL* 1.08 1.01-1.17 0.027
Pack-years 1.09 0.95-1.24 0.207
Age (years) 0.96 0.90-1.03 0.243
Overweight (kgs) 1.83 0.99-3.37 0.054
Heart disease 2.02 0.89-4.58 0.091
(*) expressed as a continuous variable


The association between exposure to a significant spill or accidental chemical release at work and symptoms suggestive of chronic bronchitis, observed in the stratified analysis, was also further evaluated. With chronic bronchitis as the dependent variable, the following confounders were included in the final model: pack-years of smoking, years at ECOPETROL (> 18 years) and age. The resulting saturated model (p=0.043) revealed the following associations:

Independent variable O.R. 95%CI p value
Spill/chemical release 1.72 1.13-2.64 0.012
Pack-years 0.95 0.84-1.08 0.435
Years at ECOPETROL>18 1.32 0.77-2.27 0.313
Age (years) 1.01 0.97-1.05 0.594

In current workers, associations between possible risk factors and elevation of at least two tests of liver function were also analyzed. In the univariate analysis, statistically significant associations were found with gram-years of alcohol use (O.R. - 2.28; 95%CI - 1.33 to 3.89), being overweight (O.R. - 3.77; 95%CI 1.60 to 8.92) and hypertriglyceridemia (O.R. - 2.11; 95%CI - 1.26 to 3.51), but not with years of employment at ECOPETROL (O.R. - 1.15; 95%CI - 0.69 to 1.92) nor any of the five work areas (Table 3C). These associations were further examined by controlling for multiple variables through logistic regression. With ">2 abnormal liver function tests" taken as the dependent variable, the resulting saturated model revealed the following associations:

Independent variable O.R. 95%CI p value
Alcohol use (gm-years) 2.14 1.35-3.39 0.006
Overweight (kgs) 3.45 1.67-7.16 0.005
Hypertriglyceridemia 1.71 1.10-2.65 0.045

With respect to possible contact dermatitis involving the upper extremities, no statistically significant associations were found with either years of employment at ECOPETROL or work in any of the five work areas, although the total number of cases of contact dermatitis (n=24) was relatively small (Tables 3B and 4B).

Statistically significant differences were observed with number of years in a given work area with respect to various measures of red blood cell number and size (a trend towards decreasing red blood cell number and increasing red blood cell indices), although no definite exposure-response patterns or trends were observed within any of the work area subgroups (Tables 3D and 4C).

Personal Sampling and Area Monitoring

In the subgroup of 33 workers who underwent personal and area monitoring, the results indicated that the ACGIH TWA (8 hour) level for benzene (32 mg/m3) was exceeded by 5 to 14-fold on two occasions. The OSHA PEL (3.2 mg/m3) was exceeded in three cases, with another three cases close to the action level. All cases except one occurred in operators in the Aromatics plant; the one exception occurred in the External Elements area, specifically in an operator at the wastewater treatment area. All workers were using respiratory protection against solvents during the time that they were in the plant area, except for the two workers with the highest exposure levels,. The two highest exposures to benzene occurred in the shift following a benzene spill. The ACGIH TWA (8-hour) level for toluene (188 mg/m3) was not exceeded in any cases, but there were three cases that exceeded the action level. These cases occurred in Aromatics and Paraffins plant operators. No exposures at or near the TWA (8-hour) level for xylenes (434 mg/m3) were observed. In an operator in the phenol unit, an estimated exposure level of 8 mg/m3 was observed, which is close to 50% of the ACGIH TWA (8-hour) level for phenol (19 mg/m3). Due to the high levels of phenol in the sample, which could have saturated the mass spectrometer, this exposure level probably represents a minimum estimate of the true exposure level. No significant exposures to other compounds were observed other than phenol, although slightly increased concentrations of cyclohexanes and 2-butanone were noted.

Correlations between personal exposure levels and urinary concentrations of biomarkers were very poor. The proportion of the variance in the biomarkers that was explained by the personal breathing zone concentrations varied from 4% to less than 1%. Since very satisfactory quality control and quality assurance was achieved for all urine samples, the reasons for this poor correlation are initially unclear. Our direct observations indicated that there were opportunities for significant dermal exposure due to the use of inadequate hand protection, but this would not explain the observed results; consequently, alternative explanations should be explored.

A review of the existing documentation on individual job histories suggested that there are reasonably complete data with respect to dates of hire, promotion, transfer and termination for each work period at the Barrancabermeja complex, as well as with respect to medical history and benefits perceived by workers' families. There was no readily identifiable information on individual or plant/area job tasks in the documentation reviewed.


1. We believe this cross-sectional study population to be representative of current workers potentially exposed to aromatic hydrocarbons at the Barrancabermeja complex. In addition, it is probable that the results obtained are representative of the health profile of current workers. With respect to retirees, because they were selected from a convenience sample, it is possible that their results may not be representative of the target population of all retirees from the Barrancabermeja complex.

2. Given the high degree of study participation, completion of the various study test components, and the reliability of the data, the databases generated by this study should prove useful in testing future study hypotheses and can be integrated with other components of the SOIP.

3. In addition to the generally "non-occupational" adverse health effects observed in this study (e.g., hypertension, diabetes, hyperlipidemias, etc.), we detected an elevated prevalence of other possible adverse health effects that would benefit from greater study to determine their relationship to the workplace, home environment and/or personal lifestyles. Specifically, this study found a high prevalence of possible respiratory pathology, contact dermatitis, athlete's foot and liver function abnormalities. Only those related to the respiratory system were found to have statistically significant associations with some limited measures of occupational exposure. In the case of the remaining pathologies, the small number of cases and/or the high prevalence of possible confounding variables and/or the lack of accurate occupational exposure data limited our ability to come to firm conclusions regarding the contribution of workplace exposures.

4. The study of associations between occupational exposures and adverse health effects would be strengthened by linking the occupational history obtained in this study to quantitative measurements of personal exposures to workplace contaminants, as long as the sampling strategy is representative of true exposures.

5. Overexposures to benzene (in the Aromatics and External Elements areas) and phenol were observed during the personal sampling and area monitoring component of this cross-sectional study. There was a lack of good correlation between personal exposure monitoring and the detection of BTX metabolites in urine. In addition, we observed the use of inadequate personal protective equipment and improper practices during the handling of organic solvents.

6. The information available at the Barrancabermeja complex on each worker's job and medical histories is sufficiently detailed and complete to allow its use as one important component in a retrospective exposure assessment study.

Study Limitations

At the outset, the study population was defined by consensus among the Aromatics Commission/PAHO and the research team (based on employee payroll lists provided to PAHO) and the cross-sectional study was primarily directed at a specific group of current workers (i.e., those with potential aromatic hydrocarbon exposure). A cross-sectional study of current workers may not be representative of the entire worker population historically exposed to aromatic solvents at the Barrancabermeja complex. This could be due to:
1. healthy worker effect;
2. exclusion of less healthy workers through company pre-employment examinations;
3. exclusion of less healthy workers through periodic examinations;
4. self-selection of certain workers out of this population, because of symptoms or other discomfort, with subsequent transfer to other areas of the complex;
5. non-participation in the study because of temporary illness or transfer to another area. This would have been more likely among the random sample of maintenance workers, rather than the exhaustive sample of current workers from the other four areas;
6. the lack of knowledge of the true denominator of retirees, since this limits the representativeness of the convenience sample of retirees that was studied.

In addition, cross-sectional studies cannot confirm cause-effect relationships, since exposures and adverse health outcomes are evaluated at a single point in time. However, the significant associations observed in a cross-sectional study can serve to generate hypotheses for future cohort, case-control or intervention trials, which could address etiological relationships more thoroughly.

Finally, one of the major limitations of this type of study relates to the lack of precision of occupational exposure measurements, since they were basically derived from the occupational history questionnaire: years of employment at ECOPETROL, work area, etc. These variables, at best, represent a crude approximation to both current and cumulative exposures to aromatic hydrocarbons and, at worst, could erroneously represent true exposures sustained by the workers.


We believe that the following recommendations cannot be separated from the collective observations and recommendations that will make up the SOIP final report.
1. This cross-sectional study identified several interesting possible pathologies that should be further evaluated through specific studies. Among potential study questions are the relationship between occupational exposures and airway diseases; between more reliable measures of exposure to aromatics and hepatic dysfunction; between more reliable measures of exposure to aromatics and complete blood cell counts; and in a more detailed study of the causes of contact dermatitis among current workers.

2. From a toxicokinetic and metabolic standpoint, it would also be useful to study the poor correlation observed between personal exposure measurements and urinary biomarkers for benzene. This study could conceivably be conducted in a small group of workers, such as the Aromatics area operators and workers in External Elements (wastewater treatment plant), and would be helpful in establishing the best use of these biomarkers in the surveillance of a benzene-exposed population.

3. We believe that it would be useful to link the occupational histories obtained during this cross-sectional study to the results of a well-designed industrial hygiene study of current exposures, and to the information on employment currently available at the Barrancabermeja complex in order to produce a reliable retrospective exposure assessment. This effort would have the benefit of establishing the basis on which to identify a cohort of workers that could then be followed prospectively. This would ultimately allow the conduct of various longitudinal studies of both morbidity and mortality, as well as a proactive approach to epidemiological surveillance.

4. The detection of a high prevalence of "non-occupational" adverse health effects (including obesity, arterial hypertension, hyperlipidemias, elevated blood glucose, etc.) and of other health effects whose relationship to the work environment remains unclear (e.g., hepatic dysfunction), suggests that these conditions should be included as health indicators in a medical surveillance program. In addition, these conditions should be targeted for specific interventions through health promotion and lifestyle modification programs.

5. Within the context of the industrial hygiene component of this cross-sectional study, specific recommendations are given regarding the selection of adequate personal protective equipment and the modification of fume hoods in the Laboratory area. In addition, a regular equipment maintenance program is recommended, as well as the establishment of worker training programs directed at the identification and control of workplace hazards.


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