Objective: The objective of this study was to assess the adverse health symptoms experienced by adultsubjects who were exposed to benzene after aflaring disaster at the BP refinery in Texas City, Texas.
Methods: A total of 2162 adults aged 18 years or older and exposed to benzene were included. Using thepatients’medical charts, we collected and analyzed data on health complaints as well as the patients’serum levels of beta-2-microglobulin and urinary excretion of phenol.
Results: A total of 11,368 health symptom complaints were reported in 2162 adults exposed to benzene.Neurological symptoms occurred most frequently (174%), followed upper respiratory symptoms(115%), cough (31%), painful joints (30%), cardiac symptoms (28%), dermatological symptoms(28%), gastrointestinal symptoms (27%), diarrhea (25%), vision symptoms (21%), and nausea/vomiting (19%). Logistic regression analysis indicated that urinary symptoms (R2=0.65) and painfuljoints (R2=0.44) were positively associated with increasing age in benzene-exposed subjects.
Conclusion: Adult subjects exposed to benzene experience a range of adverse health symptoms and analtered profile of urinary phenol, thus indicating they are at high risk of developing serious future healthcomplications. (Disaster Med Public Health Preparedness. 2017;page 1 of 9)Key Words:benzene poisoning, chemical exposure, health complaints, illness symptoms, petroleumrefinery, urinary metabolites of benzene
Benzene, a volatile organic compound, occursnaturally in the environment.1It has beenfound to be one of the major environmentalcontributors to air polluttion.1,2Benzene emissionsoccur most commonly during petroleum refiningoperations. In addition, it is one of the most widely usedorganic chemicals in the synthesis of various polymers,resins, and syntheticfibers. Environmental contamina-tion of benzene originates mainly from its industrialuses through improper discharge, especially into the air.Communities living in close proximity to petroleumrefining industries are highly susceptible to significanthealth risks due to the increased probability of theirexposure to toxic chemicals such as benzene. Exposureto benzene is associated with increased risks of devel-oping carcinogenesis, specifically, leukemia, lymphoma,aplastic anemia, and multiple myeloma.3-7In addition,the emerging evidence suggests that benzene exposureincreases the risk of developing solid tumors such asthose of lung cancer8,9and breast cancer.10-12More-over, benzene exposure can cause multiple otheradverse effects leading to impairment of hematological,hepatic, renal, cardiovascular, respiratory, nervous, andimmune functions.13-18Moreover, benzene exposurecan also affect both B-cell and T-cell proliferations,
Health Complaints of Human Exposure to Benzene
complications.29In this study, we assessed the prevalence ofadverse health symptom complaints in adults after theirexposure to benzene as a result of the BPflaring disaster.SUBJECTS AND METHODSSubjectsThis retrospective study was approved by an institutionalreview board. Subjects aged 18 years or older who wereexposed to benzene were included in this study. The details
reduce host resistance to infections, and producechromosomal aberrations.19In Texas City, Texas, a 2010flaring disaster at the BPrefinery facility that lasted 40 days led to the release ofat least 500,000 pounds of toxic chemicals, includingover 17,000 pounds of benzene into the skies.20-22Consequently, the air in nearby communities wascontaminated with these toxic emissions, whichthreatened the health of over 50,000 residents livingin the Texas City area, according to the GalvestonCounty District Clerk’sOffice.To understand the potential health effects of ambientbenzene exposure resulting from the BPflaring disaster,the University Cancer and Diagnostic Centers ofHouston, TX, is currently conducting several studies.In some of these studies, we found that benzeneexposure from the BPflaring incident significantlyaltered hematological and hepatic functions in exposedsubjects regardless of their age (children, young adults,and elderly) or smoking status.23-28In addition, wefound that children experienced a range of illnesssymptoms and an altered profile of urinary phenolafter their exposure to benzene, thus indicating theirvulnerability to potentially increased adverse health
of the subjects’selection and the procedures employed forthe clinical and laboratory evaluations were reported pre-viously.23,28Briefly, communities affected by the BP refineryemission due to theflaring event were identified initially inTexas City, Texas. Subjects exposed to the emissions wereselected from the affected communities (Figure 1). Specifi-cally, these subjects experienced an involuntary exposure tobenzene for up to 40 days following the BP refineryflaringdisaster that occurred on April 6, 2010, and lasted throughMay 16, 2010. Demographic and health symptom data were
Map showing the location of the disaster of BP refinery facility in the northern parts of Texas City, Texas. (A) Location ofTexas City, Texas. (B) Depicted intensity of benzene exposure from the BP incident in the surrounding neighborhoods ofTexas City, Texas. The red, orange, and yellow colors depict higher (red) to reduced (orange) to low (yellow) intensity ofbenzene exposure. (C) Scattered dots represent the address of the study participants who were exposed to benzene aftertheflaring incident at the BP refinery and surrounding areas. (D) A closer look at the area affected by the benzeneexposure and the address of the study participants (scattered dots). Source: Figure 1 is adapted from D’Andrea MA,Reddy GK. Detrimental health effects of benzene exposure in adults after aflaring disaster at the BP refinery plant inTexas City.Disaster Med Public Health Preparedness.April 2016;10(2):233-239.
collected and included in this analysis. The study was con-ducted according to the ethical principles of the Declarationof Helsinki. To comply with the Health Insurance Portabilityand Accountability Act (HIPAA), confidentiality of infor-mation was secured by utilizing text encryption, passwordprotection, and limited personnel involvement.
Assessment of Subjective Health Symptoms
A pre-examination questionnaire survey was conducted togather information on health symptoms in those subjectsexposed to the benzene release. An illness symptom ques-tionnaire that was originally developed for benzene-exposedchildren29by the study investigators was adopted for the adultsubjects based on the possible adverse effects of their benzeneexposure. The adverse health symptoms included in thequestionnaire survey are presented in Table 1. Although thequestionnaire was able to be self-administered, it was followedup by a face-to-face interview with each subject. Assistancewas provided for non-English-speaking individuals to com-plete the questionnaire. The survey was conducted in aclinical interview by a member of the medical staff, whoverbally reviewed all the questions in the set. The surveyincluded questions about illness symptoms, generalcharacteristics, and past medical history.
Assessment of Beta-2-Microglobulin and UrinaryPhenol
Blood and urine samples were collected from the subjects atthe time the health assessment was carried out. Serum beta-2microglobulin and urinary phenol levels were assessed by anaccredited laboratory facility (LabCorp; Laboratory Cor-poration of America, Houston, TX). Urinary phenol wasassessed as a benzene metabolite using an Agilent 5980 GCsystem (Agilent Technologies, Wilmington, DE).
Data Analysis and Statistics
Medical charts of benzene-exposed subjects were reviewedand the clinical data on illness symptoms, serum beta-2microglobulin, and urinary phenol were processed forstatistical analysis. Descriptive statistics were used to assessthe subjects’demographics, which included means andstandard deviations for each variable. Student’s t-test wasused to assess the differences between the subgroups. Multiplelogistic regression analysis was performed to assess therelationship between illness symptoms and subjects’age.The significance level was predetermined at an alpha levelof 0.05.
This study included a total of 2162 adults, aged 18 years orolder, who had been exposed to benzene from the BPflaringdisaster. The subjects’demographics are shown in Table 2.The mean age of the subjects was 43 years (range, 18-89years). There were 1243 men (57%) and 919 women (43%)
The major adverse health symptoms experienced by the adultsubjects exposed to benzene after theflaring disaster are pre-sented in Table 3. A total of 11,368 health symptoms werereported in 2162 adults exposed to benzene, indicating anaverage of 5.6 symptoms experienced by each subject. Amongthese adverse health symptoms, neurological symptoms such asunsteady gait, memory loss, and headaches occurred mostfrequently (174%) in adult subjects exposed to benzene. Upperrespiratory symptoms such as shortness of breath, sore throat,difficulty in breathing, bronchitis, nose bleeds, hoarseness, andsinusitis were the second most frequently reported symptoms(115%) among the adults exposed to benzene. Cough was
Of the 2162 subjects, 758 (35%) were African American,421 (19%) were Caucasian, 204 (9%) were Hispanic, and779 (36%) were other ethnic groups.
reported in 31% of the adults, followed by painful joints(30%), cardiac symptoms (28%), dermatological symptoms(28%), gastrointestinal symptoms (27%), diarrhea (25%),vision difficulty (21%), nausea/vomiting (19%), urinary irri-tation (12%), wheezing (4%), and other symptoms (12%).To assess the impact of gender, we evaluated the differencesin the incidence of adverse health symptoms between maleand female adults (Table 3). A total of 6275 adverse healthsymptoms were reported among the 1243 males, indicating anaverage of 5.0 symptoms experienced by each male subject.In 919 females, there were a total of 5083 adverse healthsymptoms reported, indicating an average of 5.5 symptomsexperienced by each female subject. Thus, it appears thatfemale subjects had a higher frequency of adverse healthsymptoms than did male subjects from benzene exposure.Among the adverse health symptoms, neurological (182% vs168%), dermatological (34% vs 24%), and cardiac (33% vs24%) symptoms occurred more frequently in female subjectsthan in male subjects. The incidence of other health symp-toms including upper respiratory symptoms, cough, painfuljoints, gastrointestinal symptoms, diarrhea, vision difficulty,nausea/vomiting, wheezing, and urinary symptoms was similarbetween male and female subjects.
To assess whether the subject’s age contributed to anyobserved adverse health effects from the benzene exposure, afurther analysis was performed by grouping subjects into3(<30 years,≥30 to<50 years, and≥50 years) age groupsand comparing clinical outcomes between the 3 age groups.There were 2490, 5189, and 3689 total adverse healthsymptoms reported in the<30 years (n=532),≥30 to<50years (n=981), and≥50 years (n=649) age groups,respectively.Analysis of individual adverse health symptoms indicatedthat an increasing trend in upper respiratory symptoms suchas shortness of breath, sore throat, difficulty in breathing,bronchitis, nose bleeds, hoarseness, and sinusitis was seenwith increasing age among the 3 age groups (Table 4). Theyoungest age (<30 years) group (96%) had the lowest inci-dence of upper respiratory symptoms compared with eitherthe subjects aged≥30 to<50 years (115%) or the subjectsaged≥50 years (131%). Similarly, there was an increasing trendin the incidence of dermatological symptoms, cardiac symptoms,wheezing, gastrointestinal symptoms, and nausea/vomitingsymptoms with an increase in age among the 3 age groups ofsubjects. Other adverse health symptoms appeared to be similaramong the 3 age groups of subjects exposed to benzene.The results presented in Figure 2 reveal the incidence ofadverse health symptoms among adult subjects as measured bytheir distance from the BP refinery facility. Thefindingsrevealed that most adverse health symptoms were reported inthose subjects living closest to the BP refinery facility. Of the11,368 total adverse health symptoms, 4396 were reported in
subjects living within a 5-mile radius of the refinery facility.There were 3000 and 1149 adverse health symptoms reportedin subjects living a distance of a radius of>5 to 10 miles and>10 to 20 miles, respectively, from the refinery plant. Theremaining 1650 adverse health symptoms were reported insubjects living a distance of more than a 20-mile radius fromthe refinery facility.
significantly with increasing age among the benzene-exposedsubjects (P<0.05, Fig. 3B and Fig. 3C
The association of serum beta-2-microglobulin and urinaryphenol with distance was evaluated by using scatter plots inbenzene-exposed subjects and thefindings are presented inFigure 4. The results show a downhill pattern for both serumbeta-2-microglobulin and urinary phenol levels with increasingdistance from the site of the disaster. Subjects living closer tothe refinery facility were affected more profoundly than werethose living further away from the disaster site.Multiple logistic regression analysis indicated that certainadverse health symptoms were associated positively with thesubjects’age (Figure 5). In particular, urinary symptoms
as breast,11lung, renal, and nasal cancers.35Noncarcinogeniceffects of benzene exposure include respiratory abnormalities,deteriorated renal function, central nervous depression, skinirritation, hepatotoxicity, myelotoxicity, hematologicalalterations, and immunotoxicity.18Previously, we reported that benzene exposure significantlyaltered the hematological and hepatic functions in children,adults, and elderly subjects.23-28In addition, recently wereported that children exposed to benzene experienced arange of illness symptoms and an altered profile of urinaryphenol, suggesting their vulnerability to increased adversehealth complications.29The analyses in this study sought tofurther assess the illness symptom profiles following benzeneexposure from the prolonged toxic release of the BPflaringevent in adults, building on our earlier studyfindings.Thefindings of this study show that adult subjects exposed tobenzene from the BPflaring event experienced a wide rangeof adverse health symptoms including neurological, respira-tory, cardiac, dermatological, gastrointestinal, and a host ofother adverse symptoms. Each benzene-exposed adultexperienced multiple adverse neurological symptoms suchas headaches, memory loss, unsteady gait, and dizziness.Similarly, multiple upper respiratory symptoms such asshortness of breath, sore throat, difficulty in breathing,bronchitis, nose bleeds, hoarseness, and sinusitis were seen ineach benzene-exposed subject. Over 25% of the subjectsexperienced cardiac, gastrointestinal, and dermatologicalsymptoms; painful joints; diarrhea; and cough followingtheir exposure to benzene. Currently, the literature is sparseevaluating the adverse health symptoms of benzene exposurein adults or children. A study by Gordian et al36reported thatresidents exposed to evaporative emissions of gasoline hadmore severe symptoms of asthma affecting their respiratoryhealth. Tunsaringkarn et al37reported that gas stationworkers who were exposed to benzene experienced healthsymptoms such as dizziness, headache, skin irritation, eyeirritation, fatigue, sore throat, nausea, and depression. Thefindings of our current study are comparable with thosefindings reported by Tunsaringkarn et al37in that significantproportions of subjects experienced these adverse healthsymptoms following their exposure to benzene.To determine whether the subjects’gender contributed to theobservedfindings, we assessed and compared the incidence ofadverse health symptoms between male and female subjectsexposed to benzene. The overall frequency of adverse healthsymptoms was higher in women (5.5 symptoms per femalesubject) than in men (5.0 symptoms per male subject).Previously, we reported that the overall frequency of adversehealth symptoms was higher in female children (2.9 symp-toms per female child) than in male children (2.7 symptomsper male child).29Thesefindings collectively suggest thatfemale subjects are more vulnerable than male subjects to theeffects of benzene exposure. Multiple regression analysis was
consequences and the significance of the elevated urinarylevels of phenol in subjects exposed to benzene.
Our study had some limitations and the studyfindings shouldbe interpreted as such. Foremost, this study was conductedby use of a cross-sectional design. This study design allowsonly for generating a hypothesis for further investigation andnot for investigating causality. The major limitation was alack of baseline data prior to theflaring event at the BPrefinery. In addition, this investigation was retrospective innature. Thus, it is difficult to infer causality using such a studydesign because the outcomes were measured at one time pointafter exposure to benzene. The major limitation was the lackof the subjects’baseline data prior to theflaring event at theBP refinery. Moreover, there may have been a self-report biasof our outcome classification, as the subjects were aware ofthe benzene pollution in their community. This may haveresulted in an overestimation of the reported outcomes. Tominimize this potential bias, study subjects who reportedexperiencing any adverse health symptoms were asked todescribe the health symptoms to the interviewers.
Regardless of these limitations, the results of our studyindicate that benzene exposure from the refinery disaster wasassociated with significant adverse health effects among thoseexposed subjects. Since benzene is a carcinogen, people whowere exposed to the benzeneflaring disaster need to befollowed periodically over time to detect any long-term orprogressive abnormalities and adverse health complaints.Periodic health checkups, including routine laboratory blood,pulmonary, cardiac, neurologic, and other organ functionevaluations, should be performed to monitor the long-termadverse health consequences of their benzene exposure. Thus,future longitudinal studies are required to explore theimportance and nature of the health effects on humansexposed to benzene.
Together, the results of this retrospective study indicate thatsubjects exposed to benzene experienced a broad range ofadverse health symptoms including neurological, respiratory,and cardiac symptoms; painful joints; gastrointestinal symp-toms; and dermatological symptoms. In addition, a majorityof these subjects reported cough, diarrhea, nausea/vomiting,and other adverse health symptoms following their exposureto the benzene BPflaring disaster. Thesefindings support ourprevious studyfindings in which we reported that subjectsexposed to benzene experienced significant and adversealterations in their vital organ functions, including hemato-logical, hepatic, and renal functions.8-23It is therefore crucialto monitor these subjects on a long-term basis to detectadverse toxicities of their benzene exposure, especially thedevelopment of secondary malignancies. Further prospectivestudies are required to understand the potential adverse
16. Baslo A, Aksoy M. Neurological abnormalities in chronic benzenepoisoning. A study of six patients with aplastic anemia and two withpreleukemia.Environ Res. 1982;27(2):457-465. https://doi.org/10.1016/0013-9351(82)90100-1.
17. Mandiracioglu A, Akgur S, Kocabiyik N, et al. Evaluation ofneuropsychological symptoms and exposure to benzene, toluene andxylene among two different furniture worker groups in Izmir.Toxicol IndHealth. 2011;27(9):802-809. https://doi.org/10.1177/0748233711399309.
18. Bahadar H, Mostafalou S, Abdollahi M. Current understandings andperspectives on non-cancer health effects of benzene: a global concern.Toxicol Appl Pharmacol. 2014;276(2):83-94. https://doi.org/10.1016/j.taap.2014.02.012.
The results in Figure 3 indicate the levels of serum beta-2-microglobulin and urinary phenol in subjects exposed tobenzene according to their gender and among their agegroups. Beta-2-microglobulin and urinary phenol levels werestatistically similar between male and female subjects after thebenzene exposure (P=0.6, Fig. 3A). However, the levels ofserum beta-2-microglobulin and urinary phenol increased
(R2=0.65, P≤0.01) and painful joints (R2=0.44,P≤0.01) were positively associated with increasing age inthe benzene-exposed subjects.
The detrimental effect of benzene exposure on human healthhas become a major public concern around the world.Benzene exerts both carcinogenic and noncarcinogeniceffects in humans. The carcinogenic effects of benzeneexposure include not only the hematological cancers such asleukemia3,30-32and lymphoma33,34but also solid tumors such
performed to evaluate the association between the subjects’age and individual illness symptoms among the benzene-exposed adults. Thefindings indicated that urinary symptomsand painful joints were positively associated with increasingage in the benzene-exposed subjects.The levels of beta-2-microglobulin in serum is considered tobe a marker for the activation of the cellular immune system,as well as a tumor marker in certain hematologic malig-nancies.38Therefore, in this study we measured the levels ofbeta-2-microglobulin in the serum of subjects exposed tobenzene. Although the serum levels of beta-2-microglobulinwere within the normal range (0.6 – 2.4 mg/L), levelsincreased significantly with increasing age in the benzene-exposed subjects.The association of serum beta-2-microglobulin with thedistance from the site of the disaster was evaluated by usingscatter plots in benzene-exposed subjects. Thefindingssuggested that subjects living closer to the disaster facilityhad higher levels of serum beta-2-microglobulin than didthose living further away from the disaster site, indicatingperturbations in the cellular immune system among subjectsliving closer to the disaster facility. Thesefindings furthersupport the decreased illness symptoms with distance awayfrom the disaster site in benzene-exposed subjects. However,additional studies are required to determine the precise roleof serum beta-2-microglobulin levels in subjects exposedto benzene.Phenol is one of the predominant metabolites derived fromthe metabolism of benzene and is excreted in the urine.39Themeasurement of the phenol excreted in the urine is routinelyused as a marker for benzene exposure. Therefore, in thecurrent study, we measured the amount of phenol excreted inthe urine of the subjects exposed to benzene. Thefindingsshowed that subjects exposed to benzene excreted consider-able amounts of phenol in the urine. Note that only trace orundetectable amounts of phenol are found in the urine ofhealthy subjects who were not exposed to benzene.40-42Moreover, thesefindings also revealed that the urinaryexcretion of phenol was significantly higher with increasingage among the subjects exposed to benzene.The association of urinary phenol with distance from the siteof the disaster was evaluated by using scatter plots in benzene-exposed subjects. Thefindings suggest that subjects livingcloser to the disaster facility excreted higher levels of phenolin the urine than did those living further away from thedisaster site. Thisfinding indicates that subjects living closerto the disaster facility had higher levels of benzene exposurethan did those living further away from the disaster site. Theobservedfindings on urinary phenol further support thereduction in illness symptoms with distance from the siteof the disaster in benzene-exposed subjects. Nonetheless,additional studies are warranted to assess the adverse health
health consequences of the benzene exposure from thisflaringdisaster at the BP refinery facility in Texas City, Texas.
About the Authors
University Cancer and Diagnostic Centers, Houston, Texas.Correspondence and reprint requests to G. Kesava Reddy, PhD, MHA, UniversityCancer and Diagnostic Centers, 12811 Beamer Road, Houston, TX 77089(e-mail: firstname.lastname@example.org).
1. Fenga C, Gangemi S, Costa C. Benzene exposure is associated withepigenetic changes [Review].Mol Med Rep. 2016;13:3401-3405.
2. Protano C, Scalise T, Orsi GB, et al. A systematic review of benzeneexposure during pregnancy and adverse outcomes on intrauterinedevelopment and birth: still far from scientific evidence.Ann Ig.2012;24:451-463.
3. Khalade A, Jaakkola MS, Pukkala E, et al. Exposure to benzene at workand the risk of leukemia: a systematic review and meta-analysis.EnvironHealth. 2010;9(1):31. https://doi.org/10.1186/1476-069X-9-31.
4. Smith MT. Advances in understanding benzene health effects andsusceptibility.Annu Rev Public Health. 2010;31(1):133-148. https://doi.org/10.1146/annurev.publhealth.012809.103646.
5. Costantini AS, Benvenuti A, Vineis P, et al. Risk of leukemia andmultiple myeloma associated with exposure to benzene and other organicsolvents: evidence from the Italian Multicenter Case-control study.Am JInd Med. 2008;51(11):803-811. https://doi.org/10.1002/ajim.20592.
6. Snyder R. Overview of the toxicology of benzene.J Toxicol EnvironHealth A. 2000;61(5-6):339-346. https://doi.org/10.1080/00984100050166334.
7. Marchetti F, Eskenazi B, Weldon RH, et al. Occupational exposureto benzene and chromosomal structural aberrations in the sperm ofChinese men.Environ Health Perspect. 2012;120(2):229-234. https://doi.org/10.1289/ehp.1103921.
8. Chang CC, Tsai SS, Chiu HF, et al. Traffic air pollution and lung cancerin females in Taiwan: petrol station density as an indicator of diseasedevelopment.J Toxicol Environ Health A. 2009;72(10):651-657. https://doi.org/10.1080/15287390902733515.
9. Villeneuve PJ, Jerrett M, Brenner D, et al. A case-control study of long-term exposure to ambient volatile organic compounds and lung cancerin Toronto, Ontario, Canada.Am J Epidemiol. 2014;179(4):443-451.https://doi.org/
10.1093/aje/kwt289.10. Costantini AS, Gorini G, Consonni D, et al. Exposure to benzene andrisk of breast cancer among shoe factory workers in Italy.Tumori.2009;95:8-12.
11. Hansen J. Elevated risk for male breast cancer after occupationalexposure to gasoline and vehicular combustion products.Am J Ind Med.2000;37(4):349-352. https://doi.org/10.1002/(SICI)1097-0274(200004)37:4<349::AID-AJIM4>3.0.CO;2-L.
12. Hystad P, Villeneuve PJ, Goldberg MS, et al. Exposure to traffic-relatedair pollution and the risk of developing breast cancer among womenin eight Canadian provinces: a case-control study.Environ Int.2015;74:240-248. https://doi.org/10.1016/j.envint.2014.09.004.
13. Dundarz MR, Turkbay T, Akay C, et al. Antioxidant enzymes and lipidperoxidation in adolescents with inhalant abuse.Turk J Pediatr.2003;45:43-45.
14. Dere E, Ari F. Effect of benzene on liver functions in rats (Rattusnorvegicus).Environ Monit Assess. 2009;154(1-4):23-27. https://doi.org/10.1007/s10661-008-0374-7.
15. Kotseva K, Popov T. Study of the cardiovascular effects of occupationalexposure to organic solvents.Int Arch Occup Environ Health. 1998;71(suppl):S87-S91.