IntroductionBalkan endemic nephropathy

(BEN) is a serious kidney disease (seesidebar) that occurs only in clusters ofrural villages located in tributary valleysof the Danube River in the BalkanPeninsula (Hall, 1992). Figure 1 showsthe areas in the former Yugoslavia (Ser-bia, Croatia, Bosnia, and Kosovo),Romania, and Bulgaria affected byBEN. It is believed that at least 25,000persons are suffering from BEN or aresuspected of having the disease and thatthe total number of people at risk mayexceed 100,000. BEN was firstdescribed as a distinct medical entity in1956, but it may have existed unde-

scribed for many centuries. The geo-graphic distribution of the disease hasnot changed significantly since the1950’s. Villages afflicted in the pastcontinue to have cases of BEN, whilevillages with no history of BEN (someof which are only a few miles fromaffected villages) have remained free ofthis disease.

The mysterious nature of BEN hasled people in the affected villages tolink the disease to incomprehensiblecosmic powers, and some villagers wearamulets, use pendants, perform ritualprayers, or move from the area to bespared from the disease. Because BENis confined to restricted areas of the

Balkans, many scientists speculate thatit may be caused by exposure of therural residents to some unknown toxicsubstance(s) in the environment, possi-bly coupled with a genetic predisposi-tion. Despite significant research intoBEN, its causes remain unknown.

Work by the U.S. Geological Survey(USGS) and others in the early 1990’snoted the close correspondence betweenthe location of the affected villages andthe occurrence of coal deposits, specifi-cally lignites deposited in the PlioceneEpoch 5.3 million to 1.6 million yearsago (Feder and others, 1991). Furtherresearch showed that the well water inaffected villages has measurable amounts

U.S. Department of the InteriorU.S. Geological Survey

USGS Fact Sheet FS–004–01April 2001

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Figure 1. Map showing the distribu-tion of the BEN foci in the BalkanPeninsula. The inset shows a typicalpanorama of a village in Romaniawith a BEN-afflicted population.Most of the affected villages are invalley bottoms along streams flow-ing into the Danube River.

Health Effects of Toxic OrganicCompounds from Coal—The Case of Balkan EndemicNephropathy (BEN)

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of organic compounds such as poly-cyclic aromatic hydrocarbons (PAH’s)and aromatic amines that may be toxic.The nearby Pliocene lignite deposits areunusual in that these coals release largeamounts of organic substances whenleached with water or other polar sol-vents. These coal deposits, therefore,could be a source of toxic organic com-pounds such as those found in the wellwater from the affected villages. Con-sumption of well water contaminatedwith toxic organic compounds derivedfrom the coal may be implicated in theonset of BEN.

The Pliocene Lignite HypothesisOn the basis of these preliminary

findings, USGS scientists developed thePliocene lignite hypothesis to explain theoccurrence and distribution of BEN(Feder and others, 1991; Orem and oth-ers, 1999). This hypothesis proposes thatground water leaches toxic organic com-pounds from the Pliocene lignite depositsin the steep hills surrounding the affectedvillages (fig. 2). The toxic organic com-pounds are then transported in the groundwater to wells in the affected villages,which lie in narrow alluvial valleys (fig. 1inset). People in the affected villages usethe well water (fig. 3) for drinking andcooking. Over time, the toxic organiccompounds in the water may cause pro-gressive kidney damage or accumulate inthe kidney tissue, resulting in the onset ofBEN, usually by age 40 to 60 (fig. 4).Toxic organic compounds in the wellwater originating from the Pliocene lig-nites may also be implicated in theunusually high incidence of upper urinarytract cancers in individuals with BEN.

Work currently underway to providefurther evidence to support this hypothe-sis is jointly funded by the USGS (EnergyResources Program), the North AtlanticTreaty Organization (NATO), and theRomanian Ministry of Health. This workis focusing on the affected areas in south-western Romania (study area shown infig. 1), and scientists from the USGS andthe Romanian Ministry of Health aresampling water supplies (wells andsprings) and coal mines and are conduct-ing interviews with villagers in the affect-ed area. This work will be expanded intoBulgaria in 2001 and into other countriesaffected by BEN in future years.

Lignite History and CompositionMacroscopically, the Pliocene lig-

nites from the BEN-affected areas arecomposed primarily of fossil wood;chemically, the lignites are very similarto the plant material and peat from whichthey formed (Orem and others, 1999).The ancient peat deposits that formed theRomanian Pliocene lignites were laiddown about 5 million–3 million yearsago in subtropical swamp forests whererivers entered an ancient sea in the

Dacian Basin, which occupied the site ofpresent-day Romania. Vegetation in theseancient swamps included cypress andsequoia trees, as well as smaller swampplants. The lignites that formed duringmillions of years following burial ofthese ancient peats are rich in water-solu-ble organic substances. Similar coaldepositional environments existed duringthe Tertiary (from 66.4 million to 1.6million years ago) in adjacent areas nowaffected by BEN (fig. 5).

Figure 2. Opencast coal (Pliocene lignite) mine located in the main Romanian BEN-affectedarea. Most visible is coal layer #IV (dark brown, ~25 feet thick), which underlies the entireaffected area.

Figure 3. Shallow water well typical of those used by the villagers in the BEN-affected area inthe Balkan Peninsula.

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Figure 6 shows gas chromatogramsof organic compounds extracted in thelaboratory by water from three samples:a Pliocene lignite from the main BEN-affected region of Romania, a Pliocenelignite from an affected area of Serbia,and a bituminous coal from the easternUnited States. Note the much richeryield of peaks for organic compounds inthe chromatograms from the Pliocenelignites compared to the chromatogramfrom the bituminous coal.

Geoscience and MedicineThe study of BEN demonstrates the

value of close working relationsbetween the geoscience and medicinecommunities. The discrete and relativelysmall size of the affected regions, thestable population, and the well-described clinical aspects of BEN makeit especially useful as a model for otherdiseases that may be linked to toxicorganic substances from coal. For exam-ple, U.S. States having the highest inci-dence of upper urinary tract cancers alsohave extensive low-rank coal deposits(lignites) and predominantly rural popu-lations. Geomedical research is neededto study whether these cancers arecaused by toxic organic compoundsleached from coal.

Coal deposits are present world-wide, and several direct links betweencoal combustion and disease in humanshave been documented (Finkelman,2000). Studies of BEN indicate thatcontamination resulting directly fromcoal deposits could also affect humanhealth in susceptible population groups.

Figure 4. Patient with BEN in a renal dialysisunit in Romania. Usually BEN patients do notexhibit external signs of the disease, except fora dark-yellow tint of the skin (xantochromia)

Medical Aspects of BENBEN is a disease of the kidneys culminating in end-stage renal failure, the

complete shutdown of kidney function (for a review, see Tatu and others, 1998).BEN patients must either undergo regular dialysis treatment or have a kidneytransplant. Without dialysis or a transplant, BEN patients die from uremia, thebuildup of poisonous waste products in the bloodstream causing major organ fail-ure. Most BEN patients live in rural villages and must be transported every 2–3days by ambulance to a dialysis clinic for treatment lasting 2–3 hours. Figure 4shows a patient with BEN in the dialysis clinic in Drobeta Turnu Severin, themajor town in the main BEN-affected area of Romania.

The pathology of BEN is that of a tubulo-interstitial nephropathy, whereinthe proximal tubules of the kidneys that are involved in separating waste materialfrom the blood are damaged and cease to function. The kidneys of BEN patientsare shrunken to one-third of their normal size. In many of its clinical aspects,BEN resembles analgesic nephropathy, a kidney disease resulting from long-termuse of phenacetin and acetaminophen for pain relief. In contrast to most peoplewho have kidney disease, only 20 percent of the BEN patients suffer from highblood pressure. The absence of high blood pressure is an unusual and currentlyunexplained aspect of the disease.

Another interesting medical aspect of the disease is the high occurrence ofcancers of the upper urinary tract in patients with BEN. These cancers are rare inthe general population but occur with a frequency of about 40–50 percent inBEN patients. This coincidence suggests that the toxin(s) responsible for the kid-ney disease in BEN may also be causing the high incidence of upper urinarytract cancers or that different toxin(s) from the same source (Pliocene lignites)may be responsible for BEN and the cancers.

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Modern BEN foci Tertiary basins

Tertiary land areas Pliocene lignite

Figure 5. Map of the Balkan Peninsula showing basins that existed during the Tertiary (66.4 mil-lion–1.6 million years ago); modified from Jasko (1973). Modern BEN-affected areas (yellow hereand in fig. 1) coincide with the margins of Tertiary basins. Subtropical vegetation formed peatdeposits in shallow, swampy waters along the basin margins; subsequent burial and heating ofthe peat created lignite.

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ReferencesFeder, G.L., Radovanovic, Z., and

Finkelman, R.B., 1991, Relation-ship between weathered coaldeposits and the etiology of Balkanendemic nephropathy: Kidney Inter-national, v. 40, supp. 34, p. S9–S11.

Finkelman, R.B., 2000, Health impactsof coal combustion: U.S. GeologicalSurvey Fact Sheet FS–094–00, 2 p.

Hall, P.W., 1992, Balkan endemicnephropathy; More questions thananswers: Nephron, v. 62, no. 1,p. 1–5.

Jasko, S., 1973, Lignitbildung imPliozaen in Suedost-Europa [Ligniteformation in the Pliocene of south-eastern Europe]: Braunkohle, v. 25,p. 67–71.

Orem, W.H., Feder, G.L., and Finkel-man, R.B., 1999, A possible linkbetween Balkan endemic nephropa-thy and the leaching of toxic organ-ic compounds from Pliocene lig-nites by groundwater: InternationalJournal of Coal Geology, v. 40, no.2–3, p. 237–252.

Tatu, C.A., Orem, W.H., Finkelman,R.B., and Feder, G.L., 1998, Theetiology of Balkan endemicnephropathy; Still more questionsthan answers: Environmental HealthPerspectives, v. 106, no. 11, p.689–700.

For more information, please contact:

William H. OremU.S. Geological SurveyNational Center, Mail Stop 956Reston, VA 20192E-mail: borem@usgs.govTelephone: 703–648–6273Fax: 703–648–6419

Calin A. TatuInstitute of Public HealthStr. Vasile Goldis 1–3Sc.2 Et.3 Ap.10RO–2900 Arad RomaniaE-mail: cta@med.unc.eduTelephone: 40–92–607490

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Figure 6. Gas chromatograms of laboratory water extracts of Pliocene lignites from two BEN-affected areas—Romania (A) and Serbia (B)—and of a bituminous coal from Maryland, U.S.A. (C). Peaks indicate the presence of potentially toxic organic compounds.

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