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41

1. Exposure Data

1.1 Chemical and physical data

From HSDB (2010), IPCS-CEC (2005), and

NP (2005)

1.1.1 Nomenclature

Chem. Abstr. Services Reg. No.: 84-65-1Chem. Abstr. Name: Anthraquinone;9,10-anthraquinoneSynonyms:Anthracene, 9,10-dihydro-9,10-dioxo-; anthradione; 9,10-anthra-cenedione; bis-alkylaminoanthraquinone; 9,10-dioxoanthracene;

9,10-dihydro-9,10-dioxoanthracene.RECS No.: CB4725000EINECS No.: 201-549-0

1.1.2 Structural and molecular formulae andrelative molecular mass

O

O

C14

H8O

2

Relative molecular mass: 208.21

1.1.3 Chemical and physical properties of thepure substance

Description: Light yellow crystalsBoiling-point: 380 C

Melting-point: 286 C

Vapour pressure: 1.16 10-7mm Hg at25 CSolubility in water:1.35 mg/L at 25 CDensity:1.44 g/cm3at 20 CFlash-point: 185 CRelative vapour density (air = 1): 7.16

Auto-ignition temperature:650 COctanol/water partition coefficient: log K

ow,

3.39Henrys law constant: 2.35 10-8atm.m3/

mol at 25 C (estimated)

1.1.4 Technical products and impurities

No data were available to the Working Group.

1.1.5 Analysis

A series o methods to measure anthraqui-none in different media has been reported(HSDB, 2010; able 1.1).

1.2 Production and use

1.2.1 Production

According to HSDB (2010), at least sixmethods are available or the manuacture oanthraquinone: (a) oxidation o naphthalene to

ANTHRAQUINONE

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naphthaquinone, which is then condensed withbutadiene to yield tetrahydroanthraquinone,then dehydrogenated to produce anthraquinone;(b) industrial preparation rom phthalic anhy-

dride and benzene; (c) oxidation o anthracenewith concentrated nitric acid; (d) dimerizationo styrene to 1-methyl-3-phenylindane usingphosphoric acid as a catalyst, ollowed by cata-lytic vapour-phase oxidation to anthraquinone;(e) oxidation o anthracene with chromic acidin 48% suluric acid or oxidation with air in the

vapour phase; and () condensation o 1,4-naph-thoquinone with butadiene.

In the United States o America, anthraqui-

none is listed as a chemical with a high productionvolume. As rom 1986, between 250500 tonnesper year were either produced or imported there.A major increase was then reported in 1998 and2002 when volumes reached 500025 000 tonnesper year (HSDB, 2010).

In the Peoples Republic o China, productionreached 37 500 tonnes in 2008 due to continuouslyincreasing demand (CRI, 2011).

1.2.2 Use

Anthraquinone is an important and widelyused raw material or the manuacture o vat dyes,which are a class o water-insoluble dyes that caneasily be reduced to a water-soluble and usuallycolourless leuco orm that readily impregnatesfibres and textiles. Teir principal properties arebrightness and good astness. Anthraquinone

is also used as a seed dressing or in seed treat-ments. Other major uses are as a pesticide, asa bird repellent (especially or geese), and as anadditive in chemical alkaline pulp processes in

the paper and pulp industry (HSDB, 2010).

1.3 Occurrence and exposure

1.3.1 Natural occurrence

Natural pigments that are derivatives oanthraquinone are ound in plants (e.g. aloelatex, senna and rhubarb), ungi, lichens andsome insects (HSDB, 2010).

1.3.2 Occupational exposure

Occupational exposure to anthraquinonecan occur during its production, its use in themanuacture o other chemicals or its direct use.Workers in transport-related industries are alsopotentially exposed to anthraquinone during itsrelease rom diesel and gasoline engine vehicles(see able 1.2).

Te National Occupational Exposure Survey,conducted rom 1981 to 1983, estimated that6187 workers were potentially exposed to anth-raquinone in the USA, mostly in the printing andpublishing industry (5475 workers), but also inphotographic processing machine operations, inthe air transport industry, and in geology andgeodesy (NIOSH, 1990).

42

Table 1.1 Selected methods of analysis of anthraquinone

Medium Method Detection limit Recovery

Seeds, crops and soil Electron-capture detector 0.05 ppm 94100%

Soils and sediment GC/MS 29.7 g/kg NR Rainwater GC/MS 0.050.10 ng/L NR

Filtered wastewater and natural water GC/MS 0.11 g/L NR

Airborne particulate matter Capillary GC and GC/MS NR NR

Fish tissue Capillary GC and GC/MS 0.2 ppb 72%

GC, gas chromatography; MS, mass spectrometry; NR, not reported

Adapted rom HSDB (2010)

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43

Table1.2Environme

ntaloccurrenceofanthraquinonefromcombustionsources

Source

Sample

Concentrationorreleaserates

Reference

Dieselengineautomobiles

Particulateemissions

NR

Yu&Hites(1981),C

houdhury(1982)

Dieselengineautomobiles

Particulatematter,5sample

s

47.7g/g

Layshocketal.(2010)

Dieselextract,3samples

5.23g/g

Dieselandgasolinevehicle

s,Japan

Particulateemissionsromexhaustpipes

1.352g/g

Odaetal.(1998)

Dieselvehicles

Particulatematter

1843g/g

Jakoberetal.(2007)

40.4g/g

Choetal.(2004)a

58g/g

Valavanidisetal.(2006)a

34g/g

Zielinskaetal.(2004)a

Dieselvehicles

Emissionrates

15.46g/km

Sidhuetal.(2005)

Carwithacatalyst

Carwithoutacatalystcar

Heavy-dutydieseltrucks

Emissionrates

4.4g/km

24.3g/km

23.5g/km

Roggeetal.(1993)

Heavy-dutydieseltrucks

Emissionrates

2127g/Louelconsu

med

Jakoberetal.(2007)

Vehicle-related

yrewearparticles

ND

ongetal.(1984)b

Brakelining

0.31g/g

Roaddustparticles

0.41g/g

Smallcrafgasturbineeng

ine

Particulateemissions

0.0658.49ng/m3

Robertsonetal.(1980)b

Burningcerealstraw

Organicextractsoemissions

995g/kguel

Ramdahl&Becher(1982)b

Domesticwasteuncontrolled

burningc

Open-airburnsample

Sidhuetal.(2005)

Concentration

1.72ng/L

Emissionrate

0.28mg/kg

Forestlitter

d,Amazon

Smokeparticulatematter

2.8g/m3

Radzibinasetal.(1995)b

Residentialoilburner

Particulatesamples

NR

Learyetal.(1987)b

Municipalwasteincinerators(4)

Extractsoairsamples(2/4samples)

2.99.0g/mL

Jamesetal.(1985)b

Municipalwasteincinerators,

Japan

Ontario,Canada

TeNetherlands

Flyash

2/2samples

1/2samples

1sample

NR

NR

ND

Eicemanetal.(1979)

Municipalsolidwasteincinerator,

Japan

Flyash

NR

Akimotoetal.(1997)

aCitedbyJakoberetal.(2007)

bCitedbyHSDB(2010)

c Experimentalburnohouseholdgarbage

dControlledburn

ND,notdetected;NR,notreported

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Although no data on the number o workersexposed to anthraquinone were available romoccupational surveys, a series o studies on healtheffects at a manuacturing plant in New Jersey,USA, reported that 842 workers were involvedthe production o anthraquinone dyes and inter-mediates (Delzell et al., 1989; Sathiakumar &Delzell, 2000); however, neither the number oworkers specifically exposed to anthraquinone

nor their exposure levels were provided.Anthraquinone was detected in air samples

(297 ng/m3) in a potroom where Sderbergelectrodes were used or aluminium reduction(Trane & Stray, 1986). Wei et al.(2010)meas-ured personal exposure (as ambient particles) toanthraquinone and polycyclic aromatic hydrocar-bons (PAHs) o two nonsmoking security guardsat a kerbside gate on a busy road (800010 000

vehicles per day). Te mean concentration oanthraquinone was 63.2 ng/m3 (25th percentile,26.1; 75th percentile, 86.8 ng/m3; 58 samples).Te major source o the organic carbons detectedin the personal monitors was gasoline engines.

Anthraquinone is used as a catalyst in thepulp industry to improve delignification o woodand increase pulp yield. A study designed todevelop analytical procedures or the detection

o anthraquinone in pulp process liquors oundthat the concentrations (mg/L) o anthraquinonewere 0.040.66 in filtrates rom bleaching, 0.130.75 in wash liquors, 0.511.5 in alkaline pulpliquors and 3.0170 in black liquors (Nelson &Cietek, 1983).

1.3.3 Environmental occurrence

Anthraquinone is ubiquitous in the environ-ment, and has been detected in the air, water(including surace, ground- and drinking-water),soil, plants, fish/seaood and animal tissue (seeable 1.3, able 1.4, and able 1.5). Te majorsources o environmental exposure are bothnatural and anthropogenic. Anthraquinone andother oxygenated PAHs are ormed rom directcombustion processes (see able 1.2) or thedegradation o PAHs by atmospheric oxidants(Layshock et al., 2010). Specifically, anthraqui-

none is ormed rom anthracene through photo-lytic and biodegradation processes (HSDB, 2006).Te levels o oxygenated PAHs in the soil and airhave increased in recent years (Layshock et al.,2010). Moreover, anthraquinone may be releaseddirectly into the environment through its useas a bird repellent or via various wastestreams

44

Table 1.3 Environmental occurrence of anthraquinone from industrial sources

Source Sample Concentration Reference

Near a chemical actory, ormer

Czechoslovakia

Mosses, 2/6 samples

Needles, 3/6 samplesEarthworm, 2/5 samplesAir, 1/8 samples

0.1764.95 g/g

0.4601.92 g/g0.4734.72 g/g44.5 ng/m3

Holoubek et al.(1991)a

Dye manuacturing plant Raw wastewater 49110 g/L (49110 ppb) Games & Hites (1977)a

Final effluent ND

imber production or organic andplastics production

Industrial wastewater, 2/79samples

NR Bursey & Pellizzari(1982)a

Wood preserving plant (abandoned) Groundwater 132 mg/L Middaugh et al.(1991)a

Stream water that flowedthrough site

2 g/L

Coal tar creosote waste site,Germany

Soil, 2 samples 2 and 20 g/g Meyer et al.(1999)a

a Cited by HSDB (2010)

ND, not detected; NR, not reported

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through its use as an additive in the soda andkraf chemical alkaline pulp processes in thepaper and pulp industry, and in the productiono various dyes (HSDB, 2006).

(a) Release/effluent

able 1.2summarizes studies o environmentalexposure to anthraquinone rom combustionsources, many o which detected anthraquinonein particulate matter rom vehicles with diesel orgasoline engines at concentrations ranging up to58 g/g. Estimated emission rates o anthraqui-none in diesel emission particles were reportedto be 24.88 g/mile [15.46 g/km]. Another studyreported emissions rates rom exhaust pipes o

various vehicles ranging rom 4.4 g/km orcars with a catalyst and 24.3 g/km or carswithout a catalyst to 23.5 g/km or heavy-dutydiesel trucks. Jakober et al. (2007) reportedemission rates o 2127 g anthraquinone/L ouel consumed rom heavy-duty diesel vehicles.Anthraquinone is also released as particles romthe combustion o plants, uel or waste, and hasbeen detected in municipal waste incinerators(fly ash or air samples) in Japan and Canada.Te emission rate or a sample rom an open-airdomestic waste incinerator was 0.28 mg/kg.

Anthraquinone has also been detected inthe environment near industrial or abandonedsites (able 1.3). It was ound in earthworms,mosses and ambient air near a chemical actoryin ormer Czechoslovakia; in raw waste water ata dye manuacturing plant; in industrial waste-water rom timber production or organic andplastics production; in groundwater and streamwater rom an abandoned wood preserving

plant; and in soil samples rom coal-tar creo-sote waste sites. Coal may be another source oexposure to anthraquinone, which was detected(0.7 g/L) in an extract o model coal piles (exaslignite) leached with distilled water under simu-lated rainall conditions (Stahl et al., 1984, citedin HSDB, 2006).

(b) Ambient air

HSDB (2006)reviewed inormation on andcalculated parameters related to the environ-mental ate o anthraquinone in ambient air,

water and soil. When released into the air, it isexpected to remain in the vapour and particu-late phases. Albinet et al. (2008) reported thatthe raction o oxygenated PAHs in the particu-late phase in the French alpine valleys mainlycomprised the heaviest compounds. However,most studies have measured anthraquinone inparticles. Leotz-Gartziandia et al. (2000)oundhigher levels o anthraquinone in the particulatephase than in the gaseous phase in samples o airrom near a motorway in France. Particle-phase

anthraquinone can be removed by wet or drydeposition (HSDB, 2006), and has been oundin precipitations (see able 1.5). Vapour-phaseanthraquinone is degraded in the atmosphereby a reaction with photochemically producedhydroxyl radicals, and has an estimated atmos-pheric hal-lie o 11 days. Te presence o sunlightmay accelerate the degradation o anthraquinoneby ozone in the atmosphere (HSDB, 2006).

Anthraquinone has been detected in ambient

air (usually in particulate matter) near road-ways, and in urban, suburban and rural areas(see able 1.4). In general, levels are higher in thewinter than in the summer, and in urban areasthan in rural areas. However, a study in Algeriaound higher levels in the summer, which theauthors presumed were due to increased genera-tion o ozone and hydrogen radicals by strongsolar radiation (Yassaa et al., 2001). Albinet etal.(2007)reported that anthraquinone was themost abundant oxygenated PAH detected in the

Marseilles area o France, and accounted or 20%o total oxygenated PAHs. Gasoline engines werean important source o this exposure.

45

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46

Table1.4Environme

ntaloccurrenceofanthraquinoneinambientair

Source

Sample

Concentration

Reference

Roads

Freewaytunnel,Japan

Airsamples

52g/g(extractmass)

Odaetal.(1998)a

Freewaytunnel,Japan

Airsamples5sites

2956ng/m3

Odaetal.(2001)

Dustguardrails5sites

9.2(6.314)ng/m3b

Urban/suburban

Barcelona,Spain

Organicextractsfrom

airborneparticulates

Bayonaetal.(1994)a

Spring

0.009ng/m3

Summer

ND

Autumn

0.026ng/m3

Winter

0.021ng/m3

Barcelona,Spain

Aerosolsamples

Galceran&Moyano(1993)a

Summer

0.082ng/m3

Winter

0.075ng/m3

Duisburg,Germany

Particulatematter

0.221.89ng/m3

Koenigetal.(1983)a

Munich,Germany

Particulatematter

0.96(0.161.85)ng/m3b

Schnelle-Kreis(2001)c

Augsburg,Germany

Urbanparticulatematter

0.39(0.110.58)ng/m3b

Sklorzetal.(2007)

ChamonixValley,FrenchAlps,200203

Airparticulates

Suburban(7samples)

Albinetetal.(2008)

Winter

1.42ng/m3

Summer

1.59ng/m3

Traffic(14samples)

Winter

3.60ng/m3

Summer

0.97ng/m3

MaurienneValley,FrenchAlps,200203

Airparticulates

Suburban(7samplesd)

Albinetetal.(2008)

Winter

2.76ng/m3

Summer

0.34ng/m3

Paris,France

Airparticulates

0.070ng/m3

Nicoletal.(2001)

Paris,France

Nearmotorway

Leotz-Gartziandiaetal.(2000)

Particles

Gas

~22ng/m3e

~2ng/m3e

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47

Source

Sample

Concentration

Reference

Marseillesarea,France

Airparticulates

Albinetetal.(2007)

Urban

Suburban

1.40(0.3782.57)ng/m3b

0.77(0.0732.79)ng/m3b

England,UnitedKingdom

Airparticulates

0.210ng/m3

Kellyetal.(1993)

Santiago,Chile,2000

Particulatematter

Providencia

MaradelRosarioSienra(2006)

Winter

Spring

1.58ng/m3

0.56ng/m3

LasCondes

Winter

Spring

0.67ng/m3

0.38ng/m3

oronto,Canada

Ambientairlevels

0.00090.0013ng/m3

Harkov(1986)a

CaliorniaandLouisiana,USA

Airparticulates,2/7sites

NR

Kolberetal.(1982)a

Portland,OR,USA

FebruarytoApril1984and

Februaryto

April1985

Gasphase

Particulatephase

2.5ng/m3

0.59ng/m3

Ligocki&Pankow(1989)a

StLouis,MO,USA

Airparticles

NR

Ramdahl&Becher(1982)a

LosAngeles,CA,USA,199

3

Ambientair/smog

0.3ng/m3

Fraseretal.(2000)a

SouthernCaliornia,USA,

1995

Airparticulate(12sites)

0.0110.22ng/m3

Manchester-Neesvigetal.(2003

)a

WashingtonDC,USA

Urbandust,3samplesg

1.60g/g

Layshocketal.(2010)

WashingtonDC,USA

Urbandust

h

2.24g/g

Albinetetal.(2006)

0.220g/g

Fernandez&Bayona(1992)

2.70g/g

Durantetal.(1998)i

2.03g/g

Choetal.(2004)i

Algiers,A

lgeria

Particles

Downtown

Yassaaetal.(2001)

Winter

Summer

1.0ng/m3

6.2ng/m3

Landfill

Winter

Summer

0.1ng/m3

1.5ng/m3

Rural

Chacaltaya,Bolivia

Air,2samples,1975

0.0640.065ng/m3

Cautreelsetal.(1977)

Antwerp,Belgium

Air,4samples,1976

0.571.0ng/m3

Cautreelsetal.(1977)

Japan

Airsample

2.8g/g(totalweightmass)

Odaetal.(1998)a

Table1.4(continued

)

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48

Source

Sample

Concentration

Reference

ChamonixValley,FrenchAlps,200203

Airparticulates

Altitude

Albinetetal.(2008)

Winter

Summer

0.15ng/m3

0.05ng/m3

Rural

Winter

Summer

0.57ng/m3

0.26ng/m3

MaurienneValley,FrenchAlps,200203

Airparticulates

Tigny,14samples

Albinetetal.(2008)

Winter

Summer

1.77ng/m3

0.47ng/m3

Solires,14samples

Winter

Summer

2.36ng/m3

0.13ng/m3

a CitedbyHSDB(2010)

bMeanandrange

c CitedbyMaradelRosarioS

ienra(2006)

dModanesite,nowintersampleswereavailableortheothersuburbansite

,Orelle;summersamplesatOrelle(0.37ng/m

3)werecomparablewithModanesite

e Estimatedromgraph

CitedbyNicoletal.(2001)

gSampleSRM1649b

hSampleSRM1649asamplec

ollectedin1970s,authorsuseddifferentchromatographymethods,ascitedbyAlbinetetal.(2006)

i AscitedbyAlbinetetal.(2006)

ND,notdetected;NR,notreported

Table1.4(continued

)

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49

Table 1.5 Environmental occurrence of anthraquinone in water and soil

Location or source Source/sample Concentration Reference

Surface water

Rhine river Surace water NR Meijers & van der Leer(1976)a

Baltic sea Surace and deep water 3 sites NR Ehrhardt et al.(1982)a

Iowa, USA Stream water 0.066 g/L (max) Kolpin et al.(2004)a

Drinking-water

Kitakyushu, Japan Drinking-water tap 5.2 ng/L Akiyama et al.(1980)

sukuba, Japan Drinking-water tap NR Shiraishi et al.(1985)a

Athens, GA, USA Drinking-water tap 20100 ng/L Truston (1978)a

Ottawa, Canada Drinking-water supply 1.82.4 ng/L Benoit et al.(1979a)a

Great Lakes, Canada Drinking-water 12 municipal watersupplies

Williams et al.(1982)

WinterSummer

ND63.5 ng/L0.272 ng/L

Unspecified Drinking-water treatment plants, 6 sites,June to October

0.62.1 ng/L Benoit et al.(1979b)a

Precipitation

Oregon, USA Rain, 8/9 stormsSpringAutumn

2.216 ng/L1874 ng/L

Pankow et al.(1984)a

Portland, OR, USA Rain, 7/7 storms, February to Apri l 1984 1.53.6 ng/m3 Ligocki et al.(1985)a

Norway Precipitation NR Lunde (1976)a

Soil and sediment

Roadside (traffic pollution),Czech Republic

Soil NR Zdrhal et al.(2000)

unnel roadway Soil, 5 sites 1.2b(0.22.1) g/gsoil

Oda et al.(2001)

Sewage area, Marseilles,France

Marine sediments, 9/10 sites 2400 ng/g Milano & Vernet (1988)a

Dokai Bay, Japan Marine sediment NR erashi et al.(1993)a

USA, 20 river basins,199295

22.2% o 536 sediment samples Highest, 2 100 g/kg; 50th percentile,< 50 g/kg

Lopes & Furlong (2001)a

New York Bay and NewarkBay, USA

Marine sedimentsClean-up scheme 3 (2 samples)Clean-up scheme 4 (3 samples)

1.70 mg/kg1.53 mg/kg

Layshock et al.(2010)

a Cited by HSDB (2010)b Mean

ND, not detected; NR, not reported.

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(c) Water and soil

Anthraquinone that is released into water isexpected to adsorb onto suspended solids andsediment. Experimental studies have shown

that the majority o the anthraquinone addedwas degraded within 3 days in both suracewater (82%) and groundwater (91%) (reviewedby HSDB, 2006). Natural bacterial popula-tions in groundwater and activated sludge werealso shown to degrade anthraquinone (range,50100%) in experiments that lasted between5 days and 3 weeks. Anthraquinone may also beremoved through photolysis by sunlight, and itsdirect photolysis hal-lie is about 9 minutes inaqueous solution. It is not sensitive to aqueous

environmental hydrolysis, and volatilizationis not expected to be an important actor in itsremoval (HSDB, 2006).

Studies that evaluated levels o anthraqui-none in water are reported in able 1.5. It hasbeen detected in groundwater rom industrialsites (see able 1.3), surace water and drinking-water (at concentrations up to 100 ng/L) inJapan, the USA and Canada (able 1.5), andalso in precipitations in the USA and Norway.

Although its estimated bioconcentration actoris low (12; HSDB, 2006), anthraquinone has beendetected at a concentration o 42 ng/g wet tissue(42 ppb) in bullhead catfish fish rom the BlackRiver in Ohio, USA (Vassilaros et al., 1982), andin the tissue (180.8 g/kg) o mussels rom theGuanabara Bay in Brazil (Layshock et al., 2010).

In soil, anthraquinone is predicted to beslightly mobile or immobile based on its esti-mated soil absorption coefficients o 275517 416that were determined using reerence European

soils (Gawlik et al., 1998). Similar to observationsin water, volatilization o anthraquinone rommoist or dry soil is not expected (HSDB, 2006).Biodegradation also appears to be the mostimportant actor that influences the removal oanthraquinone rom soil; 67% o the anthraqui-none added was biodegraded in a mixed soil

population within 12 weeks. Other studies havereported hal-lives in different soils o 310 days,and a study that used a mixed bacterial popu-lation ound that 6.5% o the initial concentra-tion o anthraquinone remained in the soil afer3 days (reviewed by HSDB, 2006).

Anthraquinone has been detected in thesoil rom roadways and in marine sedimentsrom areas near sewage plants in France, and inriver basins and bays in the USA (see able 1.5).McKinney et al. (1999)proposed that the ratioo anthracene to anthraquinone in marine sedi-ments could be used as an environmental markero the source o contamination. Tey measuredthe concentrations o anthracene and anthraqui-

none in several samples o coastal marine sedi-ments rom our urban harbour sites in NewEngland (USA) and two remote sites (LongIsland Sound in New York, and the SlocumsRiver, Massachusetts). Te ratio o anthracene toanthraquinone was less than 1 (0.3170.772) atthe urban sites, suggesting that the source o theexposure was predominantly discharge, whereasthe ratio at remote sites was greater than 1 (2.452.81), suggesting that the source was primarilyatmospheric deposition. Tey also evaluated the

oxidation o anthracene and reported that thecompound was stable and did not rapidly undergooxidation under normal conditions ound in themarine environment, although, under extremeconditions, it could be photo-oxidized by expo-sure to ultraviolet radiation.

1.3.4 Other occurrence

Anthraquinone has been detected in fish,mussel tissue and plants (HSDB, 2006). Exposureto anthraquinone rom ood stuffs can also occurthrough its leaching rom packaging. An experi-mental study (Louch, 2008) that evaluated themigration o anthraquinone rom an unbleachedkraf linerboard sample (representing a pizzadelivery box) ound that the mean level in the

50

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Anthraquinone

baked pizza crust was 196.1 ng, indicating a 3.6%migration o anthraquinone.

1.4 Regulations and guidelines

According to European Union (EU)Commission directive 2007/565/EC, anthraqui-none has been phased out as a repellent andattractant since 22 August 2008 in EU MemberStates (ESIS, 2010).

In the USA, anthraquinone has been acceptedby the Environmental Protection Agency as abird repellent or use near airports since 1998(US EPA, 1998).

2. Cancer in Humans

No studies o human cancer were identi-fied that evaluated exposure to anthraquinone

per se; however, a series o publications on dyeand resin workers in the USA, who were exposedto anthraquinone, was available. Tese workerswere potentially exposed to anthraquinoneduring its production or its use to manuac-

ture anthraquinone intermediates. Effect esti-mates were reported or subjects who worked inanthraquinone production areas, but they werealso exposed to other chemicals, and effectsspecific or exposure to anthraquinone were notanalysed. A study o substituted anthraquinonedyestuff workers in Scotland (United Kingdom)was also available; however, it was unclearwhether anthraquinone was used to producethe intermediates in this study (Gardiner et al.,1982), which was thereore not reviewed by the

Working Group. Te main findings o the epide-miological studies o anthraquinone dye workersand cancer risk are summarized in able 2.1.

2.1 Cohort and nested casecontrolstudies

2.1.1 USA

(a) Background

Delzell and colleagues evaluated mortalityamong manuacturing workers at a dye andresin plant in New Jersey. Te study was initi-ated because o reported cases o central nervoussystem neoplasms. Te findings were reported ina series o publications, including an analysis omortality or the initial cohort as o 1985 (Delzellet al., 1989), two nested casecontrol analyses one o central nervous system neoplasms and the

other o lung cancer (Barbone et al., 1992, 1994) that included both deaths and incident cases,and an analysis o mortality or an expandedcohort ollowed until 1996 (Sathiakumar &Delzell, 2000).

Te plant comprised three major produc-tion areas: (1) South dyes, where anthraquinonedyes and intermediates were produced; (2) Northdyes, where azo dyes and intermediates wereproduced; and (3) plastics and additives (P&A),where various resins and additives or resins

were produced. Tis section ocuses on data andfindings or workers in the anthraquinone dyearea. Production o anthraquinone ceased in1980, production o anthraquinone dye interme-diates and dye synthesis ceased in 1983 and theplant closed in 1996. Production o epichlorohy-drin (Group 2A, IARC, 2000), another chemicalproduced in the anthraquinone dye area thathas been associated with an increased risk olung cancer, was only carried out or 5 years

(196165) but potential exposure to epichloro-hydrin occurred during the production o epoxyresins in the P&A production area. able 2.2liststhe processes and the associated raw materialsor intermediates in the anthraquinone dye area(South dyes area) that could potentially conoundthe association between exposure to anthraqui-none and the risk o lung cancer.

51

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52

Table2.1Cohortstudiesofanthraquinonedyewor

kersa

Reference,

study

locationand

period

TotalNo.o

f

subjects

Follow-

up

period

Exposure

assessment

Organ

site

Exposure

categories

No.of

cases/

deaths

Relativerisk

(RR)(95%CI)

Covariates

Comments

Sathiakumar

&Delzell

(2000),

NewJersey,

USA,

195296

3266dye

andresin

manuacturing

workers(2859

men,407

women)

1952

96

Occupational

history(job

title,work

area,and

duration)

romplant

records

SMR

Age

Localreerence

All

deaths

Overall

728

0.90(0.830.97)Age,calendar

timeand

otherwork

area

Elevatedriskorlungcancer

wasalsoobservedamong

maintenanceworkersand

elevatedrisksor

other

cancers(e.g.b

lad

der,CNSand

stomach)wereobservedamong

workersemployedintheother

productionareas

.[Overlapswith

Delzelletal.(198

9)andBarbone

etal.(1992,1994)]

Lung

Southdyes:

Whitemen

otal

32

1.68(1.152.37)

Yrsincehire/yr

worked

5

11

1.37(0.682.45)

RR

Never

48

1.0(re.)

Ever

32

1.7(1.12.6)

Yrsincehire/yr

worked

5

11

1.5(0.72.9)

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53

Table2.1(continued

)

Reference,

study

locationand

period

TotalNo.o

f

subjects

Follow-

up

period

Exposure

assessment

Organ

site

Exposure

categories

No.of

cases/

deaths

Relativerisk

(RR)(95%CI)

Covariates

Comments

Barboneet

al.(1992)

NewJersey,

USA,

beore1988

Nestedcase

controlstudy*;

51whitemen

whodevelo

ped

lungtumou

rs

romthedye

andresin

manuacturing

workers

cohorta

Workhistory

obtained

romplant

personal

records;

inormation

onpotential

conounders

obtainedby

interviews

(subjectsor

nextokin)

andplant

medical

records

Lung

Workareaor

building

OR

Cigarette

smoking;

outside

employment

was

considered

butwasnota

conounder

Inaseparateana

lysis

consideringpossibleexposure

toasbestos(main

lyaconcern

amongpipe-cleaners),anon-

significantassociationwas

observedwithriskolung

cancer.Riskolu

ngcancerwas

alsooundtobeassociatedwith

exposuretoECH

whenrestricted

toconcentrationsinthelow

cumulativeexposurecategory.

*102controls(2percase)were

matchedonyrobirth,and

employmentstatusatthedate

odiagnosis(orlivinglung

cancercases),an

dwhowerenot

knowntohavediedbeorethe

dateodeathord

iagnosisothe

case.[Overlapsw

ithDelzellet

al.,1989;Barboneetal.,1994;

Sathiakumar&D

elzell,2000]

AQdyes

andECH

production

21

2.4(1.15.2)

>10ormore

yrsincefirst

employment

4.6(0.923)

AQdyeand

ECHarea

AQproduction

6

12(1.499)

AQ

intermediate

dyeproduction

8

1.8(0.65.1

)

AQdye

synthesis

8

1.2(0.52.9

)

AQdye

standardization

8

3.3(1.011)

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54

Reference,

study

locationand

period

TotalNo.o

f

subjects

Follow-

up

period

Exposure

assessment

Organ

site

Exposure

categories

No.of

cases/

deaths

Relativerisk

(RR)(95%CI)

Covariates

Comments

Barboneet

al.(1994)

NewJersey,

USA,

beore1988

Nestedcase

controlstudy*;

11whitemen

whodevelo

ped

CNStumours

romthedye

andresin

manuacturing

workers

cohorta

Workhistory

obtained

romplant

personal

records;

inormation

onpotential

conounders

obtainedby

interviews

(subjectsor

nextokin)

andplant

medical

records

CNS

Workarea,

process,line,

duty

OR

Unadjusted

[cigarette

smoking,

outside

employment,

head

radiation,

headtrauma,

historyo

epilepsy

anduseo

antiepileptic

drugswere

considered,

butwerenot

conounders]

All3casesinthe

AQworkarea

hadaninduction

timeo20yr

ormore.Routine

exposureto

ECHwasalsoassociatedwith

CNStumours(O

R,4.2;95%CI:

0.726;4exposed

cases);some

otheexposedca

sesoccurred

amongworkersw

howorkedin

AQintermediate

dyes.

*44controls(4p

ercase)

matchedbyyro

birthand

whohadnotdied

beorethe

dateodiagnosis

ordeathor

livingcases.Matchingcriterion

wasemployment

asodateo

diagnosis.[OverlapswithDelzell

etal.,1989;Barboneetal.,1992;

Sathiakumar&D

elzell,2000]

AQdyes

AQ

intermediate

dyes

3

(1.7)

Production

3

(1.7)

Laboratory

1

NR

OtherAQdyes

1

0.3(0.13.2

)

Production

1

0.3(0.13.9)

Laboratory

1

1.0(0.113)

Maintenance

0

0.0(0.04.6

)

a Findingsortheearlyupdateothecohortandeffectestimatesorworkersinproductionareasotherthananthraquinonedyeareanotincluded

AQ,anthraquinone;CI,confid

enceinterval;CNS,centralnervoussystem;ECH,epichlorohydrin;NR,notreported;OR,o

ddsratio;SMR,standardizedmortalityratio;yr,yearoryears

Table2.1(continued

)

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Anthraquinone

No data on exposure levels were available.[Te Working Group noted that the major limi-tation o these studies was that they did not assessexposure to specific chemicals; risk estimateswere calculated or employment in the variousproduction areas or or different processes. Tesestudies also had limited statistical power to detecteffects or specific cancers because o the smallnumbers o exposed cases.] able 2.1reports thefindings (overall and those or employment inanthraquinone production areas) rom the latestupdate o the cohort and the two nested case

control studies.

(b) Cohort study: 1986 follow-up

Te initial retrospective cohort included allmen (2642) who were employed at this plant orat least 6 months rom 1 January 1952 (openingo the plant) until 1 January 1985 (Delzell et al.,1989), and ollow-up was rom 1 July 1952 until31 December 1985. Subjects were classified intowork areas using work history inormationand standardized mortality ratios (SMRs) werecalculated using national rates. Excesses o lungcancer and central nervous system tumours wereound in certain subgroups o workers and theassociations were evaluated in more detail in twonested casecontrol studies.

(c) Nested casecontrol study of cancer of thelung

A nested casecontrol analysis o lung cancerwas conducted among the dye and resin workers(Barbone et al., 1992). Te cases comprised 51 (47decedent and 4 living) male white workers whodeveloped lung cancer beore 1 October 1988.wo controls per case (102) were selected romthe cohort, matched on year o birth and employ-ment status at the date o diagnosis (or livinglung cancer cases), and were not known to havedied beore the date o death or diagnosis o the

case. Workers were assigned to one o the threeproduction areas (see above) and processes withinthe production areas (processes that involvedanthraquinone are described in able 2.2),based on personnel records. Employees in eachproduction area/process were also classified byduties production, laboratory or maintenance or each o the production areas. In additionto the production categories, workers could alsobe assigned to central laboratories and central

maintenance or activities that were not carriedout in one o the production areas or services.Cumulative potential exposure to epichloro-hydrin and asbestos was calculated or eachsubject by multiplying each category o potentialcontact with epichlorohydrin by the number oyears worked in that category, and then addingthe findings or all categories. Inormation on

55

Table 2.2 Selected raw materials or intermediates used in different processes associated withanthraquinone dyes

Processes or lines Selected raw materials or intermediates

AQ production (South dyes) Anthracene, vanadium pentoxideAQ intermediate dyes (including AQsulonate, amino-AQ other substituted AQs)

AQ, suluric acid, mercury, AQ sulonates, ammonia, arsenic acid,m-nitrobenzene sulonic acid, methanol,

AQ dye synthesis AQ intermediates, aniline, substituted anilines, benzene, nitrobenzene,chorobenzene, chlorotoluenes, pyridine, alcohols, tetrachloroethylene

AQ dye standardization (final ormulation mixing, milling, drying)

Dye dusts, 2,4,5-trichlorophenol

Epichlorohydrin production Allyl chloride, chloride lime

AQ, anthraquinone

From Delzell et al.(1989),Sathiakumar & Delzell (2000)

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potential conounders was obtained rom inter-views, using a structured questionnaire, withstudy subjects or their next o kin, and romplant medical records. Subjects were also classi-fied according to high-risk employment beoreand afer working at the plant. Odd ratios (ORs)were calculated with and without adjustmentor cigarette smoking (using detailed inorma-tion on individuals) and employment in outsideindustries, but only smoking was ound to be aconounder in certain analyses. When smokingwas not ound to be a conounder in the analyses,unadjusted odds ratios were reported.

Statistically significant (or borderline signifi-cant) elevated risks or lung cancer were ound

among workers in the anthraquinone andepichlorohydrin production area (OR, 2.4; 95%confidence interval [CI]: 1.15.2; 21 exposedcases, 24 exposed controls) and, within this area,or anthraquinone production (OR, 12; 95%:CI,1.499; six exposed cases, one exposed control),and anthraquinone dye standardization (OR, 3.3;95%CI: 1.011; eight exposed cases, six exposedcontrols). Te odds ratio among workers in theanthraquinone intermediate dye productionprocess was 1.8 (95%CI: 0.65.1; eight exposed

cases, 10 exposed controls). [Te Working Groupnoted that none o the reported odds ratios wasadjusted or smoking because the authors ruledit out as a conounder in their analyses.]

Te smoking-adjusted odds ratios amongworkers with 10 or more years since first employ-ment in the anthraquinone and epichlorohydrinproduction area was 4.6 (95%CI: 0.923). Anexcess o lung cancer was also ound or employeesin the epichlorohydrin production process who

had worked in the anthraquinone productionarea (three exposed cases, no exposed controls).For all workers (in the entire plant and not just theanthraquinone production area), the odds ratioor potential exposure to epichlorohydrin was1.7 (95%CI: 0.74.1; 12 exposed cases, 18 exposedcontrols). Te risk was concentrated among indi-

viduals with low cumulative or short duration

o potential exposure to epichlorohydrin. [TeWorking Group noted that the increased risk orworkers in the anthraquinone dye area was prob-ably independent o the increased risk associatedwith exposure to epichlorohydrin because thelater analysis included only three o the 21 casesobserved among anthraquinone productionworkers.] Elevated odds ratios were also oundor some other production areas or processes, butwere not statistically significant.

(d) Nested casecontrol study of tumours of thecentral nervous system

Te relationship between central nervoussystem tumours and exposure to epichlorohy-

drin was evaluated in greater detail in a nestedcasecontrol study (Barbone et al., 1994). [TeWorking Group noted that some o the workersexposed to epichlorohydrin were also exposed toanthraquinone.] Cases included 11 (eight dece-dent and three living) white men who developedtumours o the central nervous system (sevenastrocytomas and glioblastomas, two menin-giomas and two other benign tumours) beore1988. For each case, our controls (n= 44) werematched on year o birth and employment statusat the date o diagnosis (or living cases), and werenot known to have died beore the date o deathor diagnosis o the case. Exposure was assessedas described above or lung cancer. Odds ratioswere calculated with and without adjustment orcigarette smoking, outside employment, headradiation, head trauma, history o epilepsy anduse o antiepileptic drugs. Te author stated thatnone o these were ound to be conounders, andthus unadjusted odds ratios were provided (see

able 2.1).Statistically significant risks or centralnervous system tumours were ound amongworkers in the anthraquinone dye area; the asso-ciated odds ratios and the number o exposedcases with duties involving anthraquinoneintermediate dyes and their production withinthis area were identical (OR, ; 95%CI: 1.7;

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Anthraquinone

three exposed cases). Te only other statisticallysignificant odds ratio was or workers involved inthe epoxy resin line in the P&A area; elevated butstatistically non-significant risks were observedor maintenance and production activities in theazo dye production area. [Results or epichloro-hydrin are presented here because some o theworkers exposed to epichlorohydrin were alsoexposed to anthraquinone.] Detailed analyseso routine exposure to epichlorohydrin ounda statistically significant odds ratio or routinepotential exposure (OR, 4.2; 95%CI: 0.726;our exposed cases) and acute exposure (OR, ;95%CI: 1.5; three exposed cases), and positiveassociations (not statistically significant) with

cumulative potential exposure (Ptrend = 0.11),and duration o routine potential exposure(P

trend= 0.11). Potential exposure to epichlorohy-

drin primarily occurred in the epoxy plastic andadditives division o the P&A production area.[Te Working Group noted that three o the ourepichlorohydrin-exposed cases worked in eitherthe anthraquinone intermediate dye or azo dyeareas.]

(e) Cohort study: 1996 follow-up

Te cohort was later expanded and updatedto include all (3266) workers (men and women)employed or at least 6 months rom 1 January 1952until 1 January 1996 who were ollowed until 1January 1996 (Sathiakumar & Delzell, 2000). Teaverage length o ollow-up was 27 years. Localrates were used to calculate SMRs. In addition,Poisson regression analysis was used to estimatethe lung cancer risk or subjects in a particulararea using subjects who had never worked in the

area as the comparison group and adjusting orpotential conounding by age, calendar periodand employment in other high-risk areas.

Mortality rom all causes was significantlydecreased (SMR, 0.90; 95%CI: 0.830.97; 728observed deaths). Mortality in the entire cohortwas elevated, but not statistically significantly,or several cancers including lymphosarcoma

and cancer o the colon, lung, liver, genital tissue,bladder and the central nervous system. A statis-tically significantly increased risk o mortalityrom lung cancer was ound among workers inthe anthraquinone production (South dyes) area(SMR, 1.68; 95%CI: 1.152.37; relative risk orever versus never exposure, 1.7; 95%CI: 1.12.6;32 exposed cases or both analyses). Both external(SMR) and internal (Poisson regression) analysesby time since first employment and duration oexposure among hourly paid white men showedsimilar results, with slightly higher risks amonglonger-term workers than shorter-term workersor those with less than 20 years since first employ-ment; this effect was not observed among workers

with more than 20 years since first employment.Mortality was highest among workers with 20 ormore years since first employment and durationo employment less than 5 years (see able 2.1).[Te lack o a clear exposureresponse relation-ship could be because length o employment isa poor surrogate or exposure to a carcinogenicsubstance.]

3. Cancer in Experimental Animals

Carcinogenicity studies o oral administra-tion o anthraquinone to mice and rats have beenconducted by the National oxicology Program(NP, 2005), the results o which are summa-rized in able 3.1.

3.1 Oral administration

3.1.1 Mouse

Groups o 50 male and 50 emale B6C3F1

mice were ed diets containing 0, 833, 2500 or7500 ppm anthraquinone (equivalent to averagedaily doses o approximately 90, 265 or 825 and80, 235 or 745 mg/kg body weight (bw) or malesand emales, respectively) or 105 weeks. Teincidence o hepatocellular adenoma, carcinoma,

57

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58

Table3.1Carcinogen

icitystudiesoforaladministrationofanthraquinoneinthed

iettoratsandmice

Species,strain

(sex)

Duration

Dosing

regimen,

Animals/groupat

start

Incidenceoftumours

Significance

Comments

Mouse,B6C3F

1

(M)

2yr

Oral(eed)

0,833,2

500or7500

ppm50anim

als/group

Liver(hepatocellularad

enoma):

21/50,32/50,38/50,41/4

9

P=0.011(833ppm)

P