Cadmium and its compounds

Cd và các dạng Cd trong môi trường

Potential For Occupational and Environmental Exposure to

Ten Carcinogens in Toronto

Prepared for Toronto Public Health

by Pavel Muller, Ph.D.

ToxProbe Inc.

Inc. email: mullerpavel@toxprobe.com

Tel: (416) 467-5106 Fax:(416) 423-8276

http://www.toxprobe.com

The author wishes to acknowledge the coordination, advice and assistance provided by theProject Coordinator, and the valuable advice and feedback provided on the proposal and draftreport by the Project Advisory Committee

The Project Coordinator was:

Kim Perrotta MHSc, Environmental Epidemiologist, Health Promotion and Environmental

Protection, Toronto Public Health

The Project Advisory Committee members were:

Brendan Birmingham, PhD, Senior Research Toxicologist, Standards Development Branch,

Ontario Ministry of the Environment

Ronald Macfarlane, MLS, MSc, Research Consultant

Health Promotion & Environmental Protection, Toronto Public Health

Gloria Rachamin, PhD, Toxicologist, Occupational Health and Safety Branch, Ontario Ministry of

Labour

Lou Riklik, Industrial Hygienist, Occupational Health Clinic for Ontario Workers, Toronto Office Otto Sanchez-Sweatman, MD, MSc, PhD, Public Health Consultant,

Public Health Research, Education and Development,

Hamilton Social and Public Health Services Division;

Assistant Professor, School of Nursing, McMaster University;

Research Associate, Ontario Cancer Institute/Princess Margaret Hospital,

Rich Whate, Toxics Program Coordinator, Toronto Environmental Alliance

Table of Contents

1 Executive Summary 1

1.1 C ANCER EFFECTS 1

1.2 E XPOSURES IN THE WORKPLACE 2

1.3 E NVIRONMENTAL EXPOSURES 5

1.4 S ELECTED CONTAMINANTS 7

1.4.1 1, 3-Butadiene 7

1.4.2 Asbestos 7

1.4.3 Benzene 8

1.4.4 Cadmium 9

1.4.5 Chromium 10

1.4.6 Dioxins and Dibenzofurans 11

1.4.7 Formaldehyde 12

1.4.8 PAHs 12

1.4.9 Tetrachloroethylene 13

1.4.10 Trichloroethylene 15

1.5 C ONCLUSION AND RECOMMENDATIONS 15

2 Background 18

3 Selection of Contaminants 19

4 Carcinogenic potential 20

4.1 W EIGHT OF EVIDENCE FOR CARCINOGENICITY 20

4.2 G ENOTOXICITY 24

4.3 T YPES AND SITES OF CANCER ENCOUNTERED 26

4.4 O THER EFFECTS 27

4.5 C ARCINOGENIC POTENCY 28

4.5.1 Threshold versus non-threshold dose-response effects 28

6.1 X 10-7 30

4.5.2 Estimating potency for dioxins 31

4.5.3 Estimating potency for PAHs 33

4.5.4 Estimating Dermal potency from Oral Potency 34

5 Occupational exposure 36

5.1 E STIMATION OF THE NUMBER OF OCCUPATIONALLY EXPOSED WORKERS 36

5.1.1 Introduction 36

5.1.2 Method 37

5.1.3 Results and discussion 44

5.1.4 Discussion of uncertainty 57

5.1.5 Conclusion 59

5.2 I NDUSTRIES , WORK ACTIVITIES AND EXPOSURES 60

5.2.1 Asbestos 60

5.2.2 Benzene 61

5.2.3 1, 3-Butadiene 63

5.2.4 Cadmium 64

5.2.5 Chromium 65

5.2.6 Dioxins and dibenzofurans 65

5.2.7 Formaldehyde 65

5.2.8 Polycyclic Aromatic Hydrocarbons (PAHs) 67

5.2.9 Tetrachloroethylene 69

5.2.10 Trichloroethylene 71

6 Environmental exposure 72

6.1 S OURCES OF EMISSIONS 72

6.1.1 Summary and ranking of sources 72

6.1.2 Ambient air sources 77

6.1.3 Indoor air sources 83

6.1.4 Exposures from contaminated soils 84

6.1.5 Food exposure 85

6.2 R OUTES AND PATHWAYS OF EXPOSURE 85

6.2.1 Oral 85

6.2.2 Inhalation 86

6.2.3 Dermal exposure 86

6.3 E NVIRONMENTAL LEVELS 87

6.3.1 Outdoor air levels 87

6.3.2 Ontario background soil concentrations 89

6.3.3 Toronto-area surface water, drinking water and sediment concentrations 89

6.4 I NTAKE FROM ENVIRONMENTAL EXPOSURE 92

C ADMIUM 93

7 Hazard assessment 102

7.1 P RIORITIZATION OF THE CONTAMINANTS 102

7.2 C ONCLUSION 105

7.2.1 Carcinogenic Potential 105

7.2.2 Occupational Exposure 105

7.2.3 Environmental Exposure 106

7.2.4 Health Impact 107

8 Gaps in knowledge 108

8.1 P OTENCY OF CONTAMINANTS 108

8.2 O CCUPATIONAL EXPOSURE 108

8.3 E NVIRONMENTAL EMISSIONS AND EXPOSURES 108

8.3.1 Air 108

8.3.2 Food 109

8.3.3 Sediment and surface waters 109

8.3.4 Drinking water 109

8.3.5 Local fish consumption, cigarette smoking, fireplaces and woodstoves 109

8.4 M ISSING - AN OVERVIEW OF ENVIRONMENTAL AND OCCUPATIONAL ISSUES FACING THE C ITY 110

9 References 111 Appendix A - Weight of evidence evaluation for carcinogenicity A-1

1.1 USEPA, 1986 A-1 1.2 WHO A-1 1.3 CEPA A-3 1.4 USEPA (1996) A-5

Appendix B – Profiles of contaminants……….B-1

1 Executive Summary

ToxProbe Inc has prepared this report for the Health Promotion and Environmental Protection Office ofToronto Public Health (TPH) with direction and advice offered by a Project Advisory Committee (PAC)composed of experts from community groups, the provincial government, academia and TPH Thefollowing contaminants have been selected by the PAC for this assessment:

1.1 Cancer effects

There is strong evidence to indicate that nine of the ten substances induce cancer The InternationalAgency for Research on Cancer (IARC), United States Environmental Protection Agency (US EPA) andHealth Canada have all classified these nine substances as human carcinogens or probable humancarcinogens There is less agreement on tetrachloroethylene, which has been classified as “probablycarcinogenic to humans” by IARC, “unlikely to be carcinogenic to humans” by Health Canada, and “on thecontinuum between a probable human carcinogen to a possible human carcinogen” by US EPA Theevidence considered by the three agencies suggests that this compound is possibly a weak carcinogen and

an indirect carcinogen (tetrachloroethylene breaks down under anaerobic conditions to vinyl chloride, which

is a potent carcinogen)

Some carcinogens are believed to induce cancer effects through a genotoxic event that results in anirreversible mutation in the DNA of a somatic cell These carcinogens are called initiators Thesemutagenic substances can initiate cancer even at very minute doses, even though the probability of adverseeffects occurring at low doses is minimal There is no level of exposure for these chemicals that is withoutsome risk On the other hand, some carcinogens are not mutagenic Induction of cancer by these non-mutagenic substances involves other mechanisms, such as promotion Non-mutagenic carcinogens arethought to have thresholds below which cancer risk is not expected to be increased.

There is relatively strong evidence to support the mutagenic property of five of the ten substances and/ortheir metabolites and therefore their potential to initiate cancer 1,3-butadiene, benzene, chromium (VI),formaldehyde, and polycyclic aromatic hydrocarbons (PAHs) There is evidence that both asbestos andcadmium are genotoxic, causing damage to the chromosomes, and possibly mutagenic In the case oftrichloroethylene and tetrachloroethylene, the evidence for mutagenicity is weak Dioxin and relatedcompounds are probably not mutagenic, although they are considered to be carcinogenic as promoters

Among the initiators examined, carcinogenic PAHs and chromium (VI) appear to be the most potentcarcinogens by inhalation exposure, followed by asbestos and cadmium 1,3-butadiene and benzene areabout 3 to 4 orders of magnitude less potent than PAHs and chromium (VI) Formaldehyde is a weakinitiator but a strong promoter Other than inhalation, dermal exposure to carcinogenic PAHs is of greatconcern while oral exposure to PAHs is of lesser importance However, these comparisons are donewithout taking into consideration the weight of evidence supporting the identification of a chemical as acarcinogen For example, while benzene is recognized as a human carcinogen, some individual PAHs areconsidered to be “probably” carcinogenic to humans

The order might be different if the weight of evidence could be factored into the comparison Amongsubstances for which the evidence for mutagenicity is weak, dioxins and related compounds are likely themost potent carcinogens

Section 4.0 provides the estimates of carcinogenic potency of the selected contaminants and the site andtype of cancer they induce Non-cancer effects are also listed

1.2 Exposures in the workplace

Exposure information for Ontario workplaces is currently not available The readily available information

on the levels of the selected contaminants in the workplace environment has been extracted from the

literature However, this information is mostly out of date Occupational exposures in the Toronto workenvironment are expected, in most instances, to be lower than these levels On the other hand, this reportcontains estimates of the number of workers potentially exposed to contaminants in different industrysectors in Toronto These sector- and contaminant-specific estimates are the first of their kind in Ontario.The estimates are based on the US and Finnish data from the 1980s Exposed workers are defined as thosepotentially exposed at work to levels exceeding the typical ambient air levels

Table 1.2.1 contains a listing of various contaminant-sector combinations, which were ranked among thetop 20 in terms of the number of exposed workers For example, more workers were potentially exposed totetrachloroethylene in the clothing-making industry than to any other selected contaminant in any of theselected industries In addition to sector-contaminant ranks, the table also lists other information such as thetotal number of workers potentially exposed above background levels of selected contaminants in a givensector and the rank of a sector

ToxProbe recommends that future work be focused on the sectors and contaminants with the greatestnumber of workers potentially exposed in Toronto, which are listed in table 1.2.2 These exposures relate

to tetrachloroethylene in the manufacture of wearing apparel, formaldehyde in the manufacture of furnitureand fixtures, benzene in the wholesale and retail trade, restaurants and hotels industries, in personal andhousehold services, as well as PAHs in the land transport industry The one outcome in the prioritizationexercise that may no longer be relevant to Toronto is the high ranking of benzene exposure in the wholesaleand retail, restaurants and hotel sectors The only obvious source of benzene in these sectors is indoorsmoking Smoking in public buildings and restaurants is restricted in Toronto; therefore it is likely that theactual number of workers exposed to benzene in these sectors could be much lower than predicted

Given that the information is not based on Toronto-specific data, it is recommended that the current study

be used only for planning and prioritizing of further Toronto-specific studies One study that should begiven high priority is the investigation of the prioritized sectors and contaminants to determine if workers arebeing exposed at levels of concern This investigation is important because prioritization solely on thenumber of workers exposed may not necessarily reflect the true risk priority of a given contaminant in agiven sector Even if the number of workers exposed is relatively large, the health effects need not besignificant so long as the level of exposure is low Further details are provided in section 5

Table 1.2.1 Sectors with the greatest number of potentially exposed workers to selected

Manufacture of other non-metallic mineral products 15 0.81 12 19 0.06

Percentage of Toronto workforce 0.53 0.01 1.1 0.18 0.45 0.61 2.5 3.4 0.04

The top ten ranking industries are bolded and shaded.

Table 1.2.2 Sectors and contaminants with highest above background incidence of exposure in Toronto The most important exposures are in italics.

Manufacture of wearing apparel, except footwear Tetrachloroethylene, formaldehyde, PAHs

Wholesale and retail trade and restaurants and hotels Benzene, Asbestos, PAHs

Chromium (VI)

1.3 Environmental exposures

It was not possible to obtain realistic emission estimates of the selected contaminants for the City ofToronto Environment Canada's (2001a) National Pollutant Release Inventory (NPRI) and United StatesEnvironmental Protection Agency’s (USEPA, 2001) Toxic Release Inventory (TRI) both focus on largepoint sources Large point sources will also likely be the focus for the recently announced Ontario’sMandatory Monitoring and Reporting initiative (MOE, 2001) Toronto is affected primarily by mobilesources such as cars and trucks, area sources such as residential heating, and small but numerous pointsources such as dry cleaning operations This report provides the results of ranking generated by theEnvironmental Defence Fund (EDF) based on the United States TRI data (see section 6.1) TRI collects awider range of data than NPRI and at present the TRI data set are preferred The ranking prepared byEDF is not directly applicable to the Toronto situation Many sources, which dominate TRI are not present

in Toronto On the other hand, many sources relevant to Toronto are not included in TRI Nevertheless, theEDF ranking scheme identifies important industry emission sources for the selected contaminants that may

be of concern to Toronto

Environmental levels and estimated intakes of selected contaminants by inhalation and ingestion weremostly obtained from the Canadian Environmental Protection Act (CEPA) reports The Ontario Ministry ofthe Environment (MOE) provided the levels of contaminants in Toronto’s surface waters, sediment anddrinking water Although the results show that exposure by ingestion is usually larger than exposure byinhalation, the cancer potency by the inhalation route is generally greater for the selected contaminants As

a result, residents generally experience a higher risk from a given contaminant from inhalation exposurethan from ingestion

In order to compare the relative human health impact of various selected air contaminants, the levels of thecontaminants were converted into toxic equivalency potentials (TEP) using the method developed by EDF TEP represents the number of pounds (or kilograms) of benzene (or toluene) that would have to bereleased into the air to pose approximately the same level of health risk as the reported release of a givencontaminant TEP is expressed in terms of benzene equivalents (for cancer risk) or toluene equivalents(for non-cancer health risk) Using these toxic equivalency potentials (TEPs), it was possible to estimatethat benzene, chromium and PAHs account for the majority of the cancer risk posed by the selectedcontaminants by the inhalation exposure pathway EDF did not develop TEPs for dioxins and asbestos andthey were therefore not included in the comparison (see table 1.3.1) USEPA has withdrawn its doseresponse assessment for tetrachloroethylene and has yet to finalize the dose response assessment fordioxins and furans

Table 1.3.1 Ranking of Carcinogenic Potential of Ten Carcinogens in Toronto Air

Benzene TEP % benzene TEP

The ranking exercise is limited to chemical release to the air and the results have to be interpreted withcaution According to EDF who developed the ranking scheme, TEP-weighted releases do notcharacterize the estimated increase in health risk associated with a chemical exposure and cannot becombined with information about an exposed population to predict the incidence of adverse effects Thescheme also does not take into account qualitative differences, such as the different types and locations ofcancer that chemicals may cause, or the weight of evidence supporting the identification of a chemical as acarcinogen Further uncertainty for the ranking in this report results from applying the TEP factors to theairborne contaminant levels in the outdoor air, based on the assumption that the air levels are proportional tothe quantities released in air This assumption may not hold because the contaminants may behavedifferently in the environment after being released to the air

In the USA, over 90% of 1,3-butadiene was released into the environment from mobile sources Althoughthis estimate is dated, it is likely that mobile sources continue to be important in the release of 1,3-butadienetoday Workers in the transport industry are expected to be exposed to 1,3-butadiene The main healthconcern for exposure to 1,3-butadiene is cancer of the lymphohaematopoietic system 1,3-Butadiene is agenotoxic carcinogen Other health effects include effects on the heart, blood and lung, reproductive anddevelopmental effects Available data in humans indicate that the haematopoietic system is the criticaltarget for budadiene-induced toxicity

The cancer potency estimates by inhalation for this contaminant were recently revised by USEPA andHealth Canada The two estimates are basically the same, with the USEPA potency value at 6.3 x 10-6 per

µg/m3 This corresponds to a lifetime cancer risk of one in a million if individuals are exposed daily to butadiene at 0.16 µg/m3 over a lifetime The current estimates are developed based on new humanepidemiological data although the USEPA Integrated Risk Information System (IRIS) database continues topost the previous estimate that was based on the mouse data

1,3-Environmentally, the predominant route of exposure to 1,3-butadiene is through inhalation 1,3-Butadiene ispresent in the outdoor air at an average level of 0.32 µg/m3 (range 0.03-2.20 µg/m3) in Toronto Theconcentration is expected to be higher at gasoline filling stations and in enclosed structures, such as parkinggarages and urban road tunnels (e.g 4-49 µg/m3 in parking garages) Most of the 1,3-butadiene present inthe indoor air comes from cigarette smoking Homes where smoking takes place indoors have higher levels

of 1,3-butadiene, ranging from 0.3 to 19.2 µg/m3 than smoke-free homes (0.04-1.0 µg/m3)

1.4.2 Asbestos

Asbestos was once used extensively in a variety of building materials such as fire-retardant insulation,ceiling and floor tiles in Canada Asbestos can be released from these materials to contaminate indoor air.Although asbestos is no longer used for these purposes in Canada, it is still used for some limited purposes

in Canada and can still be found in some older buildings

The main health concerns due to inhalation of asbestos fibres are asbestosis, lung cancer and mesothelioma(cancer of the thin membrane that surrounds the lungs and other internal organs) Gastro-intestinal cancerhas been shown to be associated with both inhalation and oral exposures, however the risk is generally low Asbestos exposure also leads to cardiovascular disease and depression of the immune system

Asbestos is genotoxic causing damage to the chromosomes, and likely mutagenic causing large deletions inthe DNA The inhalation cancer potency of asbestos was estimated to be 0.23 per fibre/mL (fibres permilliliter) by USEPA This corresponds to a lifetime cancer risk of one in a million if individuals areexposed daily to asbestos at an air level of 4 x 10-6 fibres/mL over a lifetime.

Inhalation is the major route of exposure for asbestos While there is no Toronto-specific information onthe levels of asbestos in the outdoor air, asbestos has been reported to be present at 3 x 10-6 to 3 x 10-4fibres/mL (or 0.1 to 10 ng/m3) in urban areas The outdoor air level in urban areas can range up to 3 x 10-3fibres/mL (or 100 ng/m3) Note that 1 gram is equal to1,000,000,000 nanograms (ng)

1.4.3 Benzene

Benzene is released into the atmosphere from both natural and industrial sources Major sources due tohuman activity that are potentially relevant to Toronto include automobile exhaust, automobile refuelingoperations and waste treatment plants A major source of benzene indoors is cigarette smoking

Benzene is a genotoxic carcinogen that is most clearly linked to acute myeloid leukemia (AML-leukemia), acancer characterized by proliferation of the myeloid tissue (in bone marrow and spleen) and an abnormalincrease in the number of white blood cells called granulocytes and their precursors, myelocytes andmyeloblasts, in the circulating blood Other health effects associated with long-term low-level exposureinclude toxic effects in the blood systems (reduction in different types of blood cells), reproductive effects(particularly in women) and depression of the immune system as a result of inhalation, oral or dermalexposure Ingestion of benzene is known to cause gastrointestinal effects in humans Exposure to highdoses of benzene either through contact with air or through skin contact leads to eye irritation and skindamage

USEPA has estimated the inhalation cancer potency for benzene at 4.1 x 10-6 per µg/m3 and the oralcancer potency at 2.9 x10-2 per mg/kg body weight/day These estimates correspond to a lifetime cancerrisk of one in a million if individuals are exposed daily to an air level of 0.24 µg/m3 by inhalation or orally to3.4 x 10-2µg of benzene per kg body weight per day over a lifetime

Inhalation is the major route of exposure for benzene The levels of benzene in the outdoor air in Torontorange from 1.3 to 3.1 µg/m3 with an average of 2.2 µg/m3 Indoor air levels may be even higher,particularly as a result of second hand tobacco smoke Benzene is frequently found in groundwater and soilwhere there has been a gasoline spill in the past, such as from leaking underground gasoline tanks Thelevel of benzene exposure may be above the minimal level of concern

1.4.4 Cadmium

In the USA, combustion of coal and oil is the main source that releases cadmium Other important sourcesthat are potentially relevant to Toronto include incineration of municipal waste, medical waste and sewagesludge Emissions released during the production of plastics, pigments and batteries also contribute tooverall cadmium exposure Cadmium is also present in cigarette smoke Even though the level of cadmium

is low in cigarette smoke relative to the total annual cadmium emissions in the city, its close proximity topeople, especially indoors, makes cigarette smoke an important source of cadmium in terms of its actualhealth impact

Cadmium is a genotoxic carcinogen that can produce lung cancer in humans when inhaled It does notappear to induce cancer when ingested Other health effects resulting from either inhalation or oralexposure include kidney disorders and anaemia The kidney is the main non-cancerous target of cadmiumsystemic toxicity with long-term exposure On the other hand, anaemia is likely brought about by reducedgastrointestinal uptake of iron from the diet Cadmium-induced anaemia is unlikely among populations thathave adequate iron intakes

US EPA has developed the cancer potency for cadmium based on human epidemiological data, whileHealth Canada chose to use animal data as its starting point Their potency estimates differ by about anorder of magnitude On the other hand, WHO decided not to provide a potency estimate, because of thehigh level of uncertainty associated with the risk assessment The USEPA inhalation cancer potency of 1.8

x 10-3 per µg cadmium/m3 air is recommended Thus, daily exposure to 5.6 x 10-4 µg cadmium/m3 air byinhalation over a lifetime corresponds to an added lifetime cancer risk of one in a million This exposurelimit based on cancer risk is lower than the exposure limit based on kidney dysfunction (0.01µg cadmium/m3air) The oral doses below which kidney effects are not expected are estimated by USEPA to be 0.5 µgcadmium per kg body weight per day in water and 1 µg cadmium per kg body weight per day in food.Exposure to cadmium occurs mainly via food for all ages among the general population, ranging from 0.21

to 0.51 µg of cadmium per kg body weight per day For the smokers, cigarette smoking is an importantsource of cadmium exposure, contributing an additional 0.053-0.066 µg of cadmium per kg body weight perday Exposure via the outdoor air is about 100 to 1000-fold lower than exposure from food The intakefrom drinking water and soil are also relatively small when compared to intake from food The averageoutdoor air concentration in Southern Ontario has been reported to be 4.2 x 10-4 µg/m3 (range: 2.4 x 10-4 to7.2 x 10-4µg/m3) Cigarette smoking adds substantially to the cadmium levels in the indoor air

1.4.5 Chromium

Chromium exists in three forms

• Metallic chromium (chromium (0)) Not much is known about the health effects of this form of

chromium However there is no reason to believe that chromium (0) is a major cause for concern

• Chromium (III) is the form of chromium that is naturally found in the environment Chromium

(III) is an essential nutrient and is not considered to be carcinogenic

• Chromium (VI) is released into the environment primarily as a result of industrial activity.

Chromium (VI) is not an essential nutrient and induces lung cancer upon long-term exposure

Electroplating, leather tanning, and textile industries release large amounts of chromium to surface waters.Coal burning may contribute to the emissions of chromium III and some chromium VI Chromatemanufacture can also be a major source for chromium (VI) but this source is not expected to be relevant inToronto

Chromium (VI) is a genotoxic carcinogen that can produce lung cancer when inhaled However, at thepresent time there is no evidence that chromium (VI) is carcinogenic when ingested Exposure to highlevels of chromium in air (above 20 ng/m3 chromium (VI)) can produce nosebleeds, ulcers, holes in thenasal septum and other respiratory effects Exposure to low levels of chromium of any form can induceallergic dermatitis Exposure to chromium (VI) may also produce reproductive effects

There is agreement among regulators regarding the cancer potency of chromium (VI) by inhalation TheUSEPA potency estimate of 1.2 x 10-2 per µg chromium (VI)/m3 is recommended In essence, exposure to8.3 x 10-5µg chromium (VI)/m3 every day over a lifetime corresponds to an additional lifetime cancer risk

of one in a million

The general population of all age groups is exposed to chromium primarily from food (about 96%, primarilychromium (III)) and to a lesser degree from drinking water, soil and air Cigarette smoking may increasetotal daily intake by 0.04 to 0.05 µg/kg/d The mean airborne concentration of total chromium in 12Canadian cities between 1987 and 1990 ranged from 3 x 10-3 to 9 x 10-3µg/m3 Chromium (VI) comprisesroughly 3-8% of total chromium in the urban outdoor air

1.4.6 Dioxins and Dibenzofurans

In Ontario, medical waste incinerators are the most significant contributors of dioxins and furans The nextmost important contributors are hazardous waste incinerators, followed by iron sintering, backyard barrelburning, steel manufacturing, diesel fuel combustion, base metal smelting, municipal waste incinerators,residential wood burning and coal-fired electrical generating station Among these sources, diesel fuelcombustion, wood burning and medical waste incineration may be most relevant to Toronto

Dioxins and related compounds (including dibenzofurans and coplanar PCBs) induce a wide spectrum ofresponses in humans and animals Theses responses are initiated by the binding of the compound to an Ahreceptor protein in the cells, which triggers a series of events including alteration of normal cellularregulation leading to various health hazards The spectrum of responses include cancer (multiple sites,particularly lung cancer and soft tissue sarcoma), chloracne (severe acne-like condition), reproductive anddevelopmental effects, suppression of immune functions, and hormonal disruption This represents acontinuum of effects

Dioxins and related compounds are not directly genotoxic They are potent promoters tetrachlordibenzo-p-dioxin (TCDD) is the most toxic member and the toxicity of all other members isexpressed as toxic equivalents (TEQ) of TCDD Estimation of the cancer potency for dioxins is acontroversial issue and the USEPA potency estimate for dioxins differs significantly from the estimatesdeveloped by WHO and Health Canada USEPA assumed a non-threshold dose-response relationship andarrived at a cancer potency of approximately 1 x 10-3 per pg TCDD/kg/day This corresponds to an addedlifetime cancer risk of one in a million if individuals are exposed daily to 1 x 10-3 pg TEQ/kg/day for alifetime Both WHO and Health Canada consider dioxins and related compounds as threshold carcinogensand derived a tolerable daily intake of 10 pg TEQ/kg/day to protect humans from the carcinogenicproperties of dioxins The WHO and Health Canada approaches are recommended (Note that 1 gram isequivalent to 1,000,000,000,000 picograms (pg))

2,3,7,8-Altered development is among the most sensitive health endpoints resulting from dioxin exposure Evidence

in animals suggest that prenatal dioxin exposure has the potential to disrupt a large number of criticaldevelopmental events at specific developmental stages, ranging from death inside the womb, disruption oforgan structure development, permanent impairment of organ function, alteration of learning behaviour andimpaired reproductive system to immune suppression after birth WHO has developed a tolerable dailyintake of 1-4 pg TEQ/kg/day on the basis of reproductive and development effects

The Canadian Council of the Ministers of the Environment (CCME) is currently developing Canada-wide Standards for dioxins and furans and is aiming for virtual elimination of this family of compounds.

Dioxins and related compounds can be transported a long distance in the air, persist in the environment andaccumulate in the food chain Food is the major source of exposure to dioxins and furans as they tend tobioaccumulate in the food chain Age-specific estimates of average total exposure to dioxins and furans forGreat Lakes basin residents range from 1.20 pg TEQ/kg/day in adults 20 years of age and older to 57.05 pgTEQ/kg/day in breast-fed infants under six months of age Assuming a 70-year lifespan and being breast-fed as an infant, the daily intake for the Great Lakes Basin general population (including Torontonians),

averaged over a lifetime, is estimated to be 2.60 pg TEQ/kg/day Since the fish in the Great Lakes containsubstantial levels of dioxins and furans, individuals who eat a lot of sport fish are expected to have a highlevel of exposure For example, adults 20 years of age or older, who eat an average 21.3 grams of GreatLakes sport fish per day would have a total exposure of 4.25 pg TEQ/kg/day.

Due to the effect of dioxin exposure at critical stages of development, the developing fetuses are the mostsensitive subpopulations Infants, particularly the breast-fed ones, are sensitive to the effect of dioxinsbecause of their high levels of exposure However, due to nutritional, immunological and psychologicalbenefit of breast-feeding, Health Canada does not consider it reasonable to advise against breast-feeding

1.4.7 Formaldehyde

In the USA, more than half of formaldehyde releases to the environment originate from mobile sources.Humans can also be exposed to formaldehyde present in the indoor air due to off-gassing from buildingmaterials, especially pressed-wood products, consumer goods, environmental tobacco smoke andcombustion appliances A quantitative risk assessment would be required to determine which of thesesources has greater impact on human health

Formaldehyde is considered to have weak tumour initiating (genotoxic) and strong tumour promoting genotoxic) properties It is a highly reactive substance that is irritating to tissues with which it has directcontact and its effects are mostly experienced at the point of contact For example, exposure to airborneformaldehyde leads to symptoms of irritation of the eyes and the upper respiratory tract Skin irritation andallergic contact dermatitis can result from skin contact with liquid formaldehyde and the gastrointestinaltract can be irritated with oral exposure Despite inconsistent evidence in humans, formaldehyde isconsidered a probable human carcinogen based on sufficient evidence that inhalation induces malignantnasal tumours in rats

(non-Both USEPA and Health Canada are currently reviewing the dose-response relationship for formaldehyde.The most recent cancer potency estimate proposed by USEPA is 2.8 x 10-7 per µg/m3 This corresponds

to an additional cancer risk level of one in a million for a lifetime exposure to 3.6 µg/m3 of formaldehyde.The most significant route of exposure to formaldehyde is inhalation, particularly while indoors Theaverage formaldehyde level present in the outdoor air in Canada is 3.3 µg/m3 The indoor air levels inhomes and offices are generally higher than the outdoor levels due to off-gassing of formaldehyde fromvarious home products and cigarette smoking The average indoor air level of formaldehyde in theCanadian homes is estimated by CEPA to be 35.9 µg/m3 Assuming people spend 3 hours outdoors and 21hours indoors on a daily basis, the mean 24-hr time-weighted average formaldehyde airborne level to whichCanadians are exposed is estimated to be 36 µg/m3

1.4.8 PAHs

Toronto does not have large point sources of PAHs within its boundaries but there are significant areasources (home heating), mobile sources (car and truck traffic mostly) and a number of other smallersources PAHs are routinely found in Toronto soils, primarily as a result of past historical activities

PAHs have been shown to induce a number of toxic effects besides cancer PAHs can irritate therespiratory tract, the eyes, and the skin in occupational settings Extreme environmental conditions (e.g.heavy exposure to forest fire smoke) may also trigger these effects Some PAH-rich mixtures arecarcinogenic to both humans and animals Individually, some PAHs are carcinogenic to animals whileothers are not Some are genotoxic and others are not Other effects include suppression of the immunesystem, disruption of the female and male reproductive systems, and impairment of fetal development Thedoses required to induce developmental effects are generally similar or somewhat higher than thoserequired for a carcinogenic response Benzo[a]pyrene (B[a]P) is the most toxic member of the PAHfamily of compounds.

There are generally two approaches used to estimate the cancer potency of a PAH-rich mixture Oneapproach involves summing up the risk from exposure to individual PAHs, such as practised mostly inNorth America (Health Canada, USEPA, California EPA) This approach has been shown tounderestimate the risk in many situations, probably because a typical mixture usually has hundreds of PAHsand the speciated approach considers only about a dozen PAHs In Europe, PAH-rich mixtures areassessed as a whole (Netherlands, World Health Organization) The Ontario Ministry of the Environment(MOE) has thoroughly evaluated the two approaches and recommended that evaluation of PAH-richmixtures be conducted on a whole mixture basis The whole mixture approach is the model that ToxProberecommends MOE has established the cancer potency for B[a]PS (B[a]PS represents the potency of aPAH-rich mixture, expressed in terms of B[a]P content.) as 2.3 x 10-2 per µg B[a]P/m3 by inhalation, 2.9per mg/kg/day by ingestion and 95 per mg/kg/day by dermal exposure These values correspond to anadded lifetime cancer risk of one in a million if individuals are exposed to a PAH-rich mixture that contains4.3 x 10-5µg B[a]P/m3 by inhalation, or yields an intake of 3.4 x 10-4 µg B[a]P/kg/day by ingestion or 1 x

10-5µg B[a]P/kg/day by dermal absorption (Note that 1 g is equivalent to 1000 mg which is equivalent to

1000 µg.)

The average concentration of B[a]P in Toronto outdoor air is approximately 3 x 10-4 µg/m3 The levels aregenerally higher in the winter (3.6 x 10-4µg/m3) than in the summer months (1.4 x 10-4µg/m3) Althoughfood is the major source of exposure to B[a]P, since B[a]P is a more potent carcinogen when inhaled thaningested, the risk of stomach cancer from oral intake may not be higher than the risk of lung cancer due toinhalation exposure In general, due to winter heating, the daily intake of B[a]P is about one order ofmagnitude higher in the winter than in the summer months Because people spend more time indoors, theindoor air contributes more to the total daily intake of B[a]P The exposure is further increased in situationswhere the residents supplement home heating with a fireplace and where cigarette smoking takes place inthe homes

1.4.9 Tetrachloroethylene

Tetrachloroethylene may be important in Toronto because of its use in the dry-cleaning industry andclothing industry Furthermore, tetrachloroethylene may biodegrade under anaerobic conditions intotrichloroethylene and eventually into vinyl chloride (a potent carcinogen) Both trichloroethylene and vinyl

chloride are considered more toxic than tetrachloroethylene All three contaminants are routinely found inthe soil and groundwater of contaminated sites in southern Ontario.

According to Agency for Toxic Substances and Disease Registry (ATSDR), the pattern oftetrachloroethylene use in the USA are as follows: 55% for chemical intermediates, 25% for metal cleaningand vapour degreasing, 15% for dry cleaning and textile processing, and 5% for other unspecified uses.Since the chemical industry constitutes only a small proportion of Toronto industry, it is expected that drycleaning and textile processing will contribute a greater proportion of the total emissions in Toronto ascompared to the general USA use pattern Dry cleaning use is important from an environmentalperspective given the proximity of dry cleaning operations to commercial and residential buildings wherepeople spend a lot of time

Long term exposure to low levels of tetrachloroethylene has led to subtle neurological effects Kidneyeffects have also been observed, especially in people occupationally exposed There is strong evidence thattetrachloroethylene affects the liver in animals, however, evidence in humans is weaker It is very likelythat the tetrachloroethylene metabolic product responsible for liver toxicity in animals is relatively minor inhumans

Tetrachloroethylene is a weak mutagen in humans and the weight of evidence for its carcinogenicity is low

as compared to the other nine substances considered It appears that the mutagenic activities of

tetrachloroethylene in the in vivo rodent tests are due to the activities of its glutathione conjugates.

Glutathione conjugation is of less importance as a metabolic process in humans than in rodents It istherefore expected that tetrachloroethylene may induce only minimal genotoxic effects in humans at lowdoses

There is no consensus in the scientific community and regulatory agencies with respect to whether

tetrachloroethylene induces cancer effects in humans IARC has classified it as probably carcinogenic

to humans Health Canada has revised its classification downwards to unlikely to be carcinogenic to humans Most agencies’ positions lie somewhere between those of IARC and Health Canada For

example, the European Union considers tetrachloroethylene not classifiable as to its carcinogenicity Though USEPA has proposed to classify tetrachloroethylene as a probable human carcinogen, the proposalwas not supported by the Science Advisory Board of USEPA US EPA’s current official position regarding

this contaminant is “on the continuum between a probable human carcinogen (sufficient evidence from animals studies but inadequate evidence or no data from epidemiological studies) and a possible human carcinogen (limited evidence for carcinogenicity in animals, inadequate human carcinogenicity data)” Health Canada has developed a potency estimate for tetrachloroethylene based

on its adverse effects other than cancer Despite IARC’s classification (IARC is a WHO agency), WHOalso chose to evaluate human health risk from exposure to tetrachloroethylene based on its critical toxicendpoints other than cancer For the purposes of risk assessments and standard setting, the author supportsthe approach taken by Health Canada and WHO However, for the purposes of this report, this compoundcan be treated as a possible carcinogen that may be weakly and perhaps indirectly carcinogenic

The recommended potency estimates for tetrachloroethyene are the values developed by WHO for air and

by USEPA for ingestion These estimates suggest that exposure to an airborne concentration of 250 µg/m3

daily by inhalation and a daily oral dose of 0.01 mg/kg/day are likely to be without any risk of adverseeffects during a lifetime.

The average tetrachloroethylene levels in the outdoor air in eleven Canadian cities range from 0.2 to 5

µg/m3 The indoor air levels are about 5.1 µg/m3 Since people spend most of their time indoors, the timespent indoors makes the greatest contribution to the overall exposure to tetrachloroethylene, while theingestion of drinking water (generally) makes a minor contribution The use of household products thatcontain this compound and the residual tetrachloroethylene present in freshly dry-cleaned clothing are likelythe predominant reason why the indoor air levels are generally higher than the ambient air levels.

1.4.10 Trichloroethylene

Degreasing operations are the biggest source of occupational exposures to trichloroethylene and the biggestsource of emissions to the environment Some trichloroethylene is released during household and industrialdry-cleaning Trichloroethylene is also used as a solvent Evaporation and losses from adhesives, paintsand coatings may contribute to exposure indoors Trichloroethylene may be biotransformed under suitableanaerobic conditions into vinyl chloride, which is a more potent carcinogen These contaminants areroutinely found in the soil and groundwater of contaminated sites in Southern Ontario

The data in support of mutagenicity of trichloroethylene are equivocal, consistent with a weak, indirectmutagen Toxicants, which are not mutagenic are often assumed to have a threshold below which theyhave no effect Nevertheless, Health Canada, California Environmental Protection Agency and WorldHealth Organization all assume a no threshold dose-effect relationship for trichloroethylene

Other health effects include depression of the central nervous system when inhaled and skin rashes ondirect skin contact with trichloroethylene Liver and kidney damage and developmental effects(behavioural and heart abnormalities in pups) have been observed in animals exposed by ingestion andinhalation It is not clear how humans are compared to animals in terms of sensitivity to these effects

Health Canada’s cancer potency estimates are recommended The cancer potency for inhalation isestimated at 6.1 x 10-7 per µg/m3 and for oral ingestion is 1 x 10-4 per mg/kg/day These values correspond

to an added lifetime cancer risk of one in a million if individuals are exposed daily to an airborne level of 1.6

µg/m3 by inhalation or 6.7 x 10-3 mg/kg/day by ingestion

Indoor air is the major source of exposure to trichloroethylene in the general population, while ambient air,drinking water and food make only minor contributions The outdoor air levels in Toronto range from 0.32

to 2.8 µg/m3, however, the indoor air levels are higher averaging 1.4 µg/m3

1.5 Conclusion and recommendations

The adverse effects of the selected substances are generally well recognized, although there does not seem

to be a regulatory consensus regarding the ability of tetrachloroethylene to induce cancer in humans

There are also questions regarding the potency estimates derived by the various agencies for dioxins andPAHs They can differ significantly The report examines the evidence and makes specificrecommendations in this area ToxProbe recommends that the City periodically review the advances made

in this area by leading regulatory bodies

Very little up to date information is available regarding the exposure levels of the 10 selected substances inthe workplace The information from readily available reports from around the world is out of date and doesnot provide reliable estimates of exposure levels in Toronto’s work environments ToxProbe considersassessment of worker exposure to be a high priority Reliable information about worker exposure is bestobtained on an industrial sector-by-sector basis Within each sector, specific processes and activities, whichlead to high exposures, need to be identified This report has identified the sectors expected to have thegreatest number of workers exposed above background levels to the ten carcinogens in Toronto Thesesectors include the transport industry, furniture manufacturing, clothing industry, personal and householdservices and others as listed in table 1.2.1 It is recommended that these sectors be the focus of any follow-

up study

ToxProbe recommends expanding estimation of the number of exposed workers to other carcinogens usingthe same method CAREX lists 139 contaminants and mixtures The expanded study needs to bemethodologically compatible with the current one so that cross-study comparisons between contaminantsand sectors can be made

Ranking of the ten substances in terms of impact on human health due to environmental exposure is difficultwithout conducting a health risk assessment Most of the contaminants examined act as non-thresholdcarcinogens while others act either as threshold carcinogens (e.g dioxins) or have health effect other thancancer as the critical toxic endpoint (e.g tetrachloroethylene) Furthermore, while air exposure is the majorpathway for inducing health risk for most of the selected contaminants, food ingestion is the most importantsource for health risk due to dioxins and related compounds

In terms of environmental exposure, obtaining good estimates of emissions from mobile sources such ascars and trucks, area sources such as home heating, and small point sources such as dry cleaning, isrecommended to be the top priority These sources are expected to have the greatest overall impact onhuman health in Toronto For this reason, it is recommended that the City proceed on a sector-by-sectorbasis The information contained in this report can be used to prioritize the emitting sectors for thisexercise

The second environmental priority is to obtain more reliable, Toronto-specific estimates of indoor airexposure It needs to be stressed that the exposure that people receive by inhalation indoors often is thedetermining factor for the level of overall environmental health concern

The third environmental priority is to determine the exposures from sources which are heavily influenced bylifestyle factors For example, burning of wood in fireplaces can produce very high levels of PAHs andother contaminants both indoors and outdoors in the surrounding area The exposure could lead tosignificant health risk to users and their neighbours At present, the City may not have information on thenumber of households that use woodstoves and fireplaces, the duration and frequency of use Consumption

of home-grown produce on contaminated soil is another important source of exposure In order to assess

this parameter, it would be desirable to establish the number of households consuming home-grownproduce, the proportion of home-grown produce consumed annually and the range of contamination found

in Toronto grown produce

This report attempts not only to summarize the existing data, but also to make comparisons of impact wherethe data permit The toxicity, release and human exposure of individual chemicals have been estimated inmany jurisdictions There has been less success in utilizing the available information to paint acomprehensive (big picture) picture of the state of occupational and environmental risk from thesechemicals Such an overview could be used to prioritize occupational and environmental issues in aninformed manner A systematic approach of this sort would also help to identify the data gaps better.Developing a systematic approach to environmental and occupational health based on good data wouldallow the City to accomplish more with its limited resources Working towards developing such a big picture

is strongly recommended This is ToxProbe’s main recommendation

2 Background

Toronto Public Health is a member of the Toronto Cancer Prevention Coalition One of the workinggroups of the Coalition is focused on occupational and environmental carcinogens The purpose of thisproject is to provide a comprehensive overview of the health effects and exposure information available onten toxic substances that are expected to be common in Toronto workplaces and/or environment Theprepared report will provide the basis for a report to Toronto’s Board of Health and may be used as abackground report by the Coalition The goal is to provide a qualitative evaluation of the health impact theselected carcinogens may have on Toronto populations at work, at home or during other activities inToronto

Dr Pavel Muller of ToxProbe Inc has prepared this report for the Health Promotion and EnvironmentalProtection Office of Toronto Public Health (TPH)

3 Selection of Contaminants

There are many ways by which contaminants can be prioritised Factors that can be taken intoconsideration in the decision can include toxicological properties of the contaminants, the level of emissionsfrom different industries found in Toronto (by means of emission factors), the size of the populationaffected and the magnitude of exposure of the exposed populations, the route of exposure, the persistence

of the contaminants, adequacy of federal and provincial regulations, and the quality of the scientificknowledge

The Project Advisory Committee has developed a list of contaminants to be assessed for their carcinogenicimpact in Toronto These contaminants are selected based on their carcinogenic potencies, the likelihoodthat there are sufficient sources within Toronto to justify investigation and other factors The list ofcontaminants selected for evaluation is presented below

4 Carcinogenic potential

4.1 Weight of evidence for carcinogenicity

Within the scientific literature, reports vary in their quality and some reports contradict each other TheInternational Agency for Research on Cancer (IARC) was the first organisation to develop a weight ofevidence scheme for cancer agents A panel of international experts systematically evaluates the evidence

of carcinogenicity, classifies each agent and publishes a summary of the evidence which includes therationale used to support the agent’s classification IARC is an agency of the World Health Organization(WHO)

Although the IARC ranking continues to be highly respected, other agencies have developed similar rankingschemes Of these, the one published by the USEPA (1986) is probably the most influential In 1996,USEPA replaced its ranking scheme based on letter ranks with a new descriptive scheme, which takes intoaccount a wider range of data (see appendix A) The USEPA’s 1986 scheme is still widely use, in partbecause the evaluations based on this earlier ranking scheme continue to be reported in the Integrated RiskInformation System (IRIS) database The ranking schemes by IARC and USEPA (1986) are quite similar.Although both organisations place a greater emphasis on good human epidemiological data than on animaldata, USEPA has traditionally placed heavier emphasis on animal data than IARC Even though the newUSEPA (1996) ranking scheme has been in use for a few years, the number of agents ranked by thisscheme is relatively small and thus it is not yet as widely used as the older scheme

In Canada, Health Canada has developed a carcinogen-ranking scheme under the Canadian EnvironmentalProtection Act (CEPA, 1994a) based on the IARC ranking scheme CEPA’s scheme consists of morecategories and subcategories and is not very compatible with those of IARC and USEPA CEPAdistinguishes between genotoxic and non-genotoxic carcinogens, and gives the latter group a lower rankingwhen epidemiological evidence is inadequate

Some US states, including California, have their own rankings So do many European countries (seeMoolenaar, 1994) A comparison of the key ranking schemes is summarised in table 4.1.1 Further detailsabout the various ranking schemes are available in Appendix A

Table 4.1.1 Comparison of three well known weight of evidence classification schemes for

carcinogens

Strength/Type of Evidence Weight of Evidence Classification

USEPA 1 IARC (WHO) 2 CEPA 3

Little or no human evidence, strong animal

Good evidence for absence of

? – Indicates imperfect fit

The carcinogenicity ranking of the selected contaminants is presented in table 4.1.2 In general, whenranking is available from more than one agency, there is a good agreement between the ranks assigned bythe three agencies The exception is tetrachloroethylene

There is no consensus in the scientific community and regulatory agencies with respect to whethertetrachloroethylene induces cancer effects in humans The judgement regarding tetrachloroethylenecarcinogenicity ranges from probably carcinogenic to humans (IARC, 1995a; Cal EPA, 1991) to unlikely to

be carcinogenic to humans (CEPA, 1996) Most agencies’ positions lie somewhere between those ofIARC and CEPA For example, the European Union (Beck, 2000) considers tetrachloroethylene notclassifiable as to its carcinogenicity On the other hand, US EPA’s official position (cited in ATSDR, 1995)

is that tetrachloroethylene is on the continuum between group B2 (probable human carcinogen) and group C (possible human carcinogen)

There is a general agreement that the human data are by themselves insufficient to definitively identifytetrachloroethylene as a carcinogen There is also a good agreement on the toxicity and carcinogenicity oftetrachloroethylene in rodents The key area of contention for tetrachloroethylene relates to whether rodentdata can be directly applied to humans

The following excerpt from a CEPA (1993d) report summarises CEPA’s position on tetrachloroethylene.

Generally, a substance for which there is adequate evidence of carcinogenicity in 2 species of laboratory animals (as observed in the NTP carcinogenesis bioassay for tetrachloroethylene) would be categorized in Group II (probably carcinogenic to humans) …

Since the observed increase in the incidence of renal tumours in male rats and hepatic tumours in male and female mice exposed to tetrachloroethylene are likely species- specific responses, both of which appear to be induced by mechanisms that are not relevant to humans or, at least, for which humans are likely to be much less sensitive, the results considered most pertinent in assessing the weight of evidence for carcinogenicity are the small increases in the incidence of spontaneously occurring mononuclear cell leukemias in a single species (i.e., male and female F344 rats) in the NTP bioassay, in which the incidence of this tumour in the non-exposed (control) rats was higher than that observed in historical controls (NTP, 1986) The proportion of animals with this tumour

in the high-dose group of males and females was 74% and 58%, respectively, compared

to 56% and 36% in the concurrent control groups and 29% and 19% in historical controls (NTP, 1986).

On the basis of this argument, CEPA (1993b) assigned to tetrachloroethylene the ranking of III (Possibly Carcinogenic to Humans), and later downgraded the ranking (Health Canada, 1996) to IV (unlikely to be

carcinogenic to humans)

The route of exposure is an important issue that has to be considered in determining the weight of evidencefor carcinogenicity Some compounds (e.g dioxins) exert their effect once they are absorbed anddistributed throughout the general body tissues For such contaminants, the difference in carcinogenicity bydifferent routes of exposure is most likely a function of the level of absorption and distribution (i.e.bioavailability), depending on the route of exposure

Other compounds (e.g PAHs such as benzo[a]pyrene (B[a]P)) are also activated near the site of uptake.Although such compounds may be carcinogenic at some distance from the site of entry if the dose is bigenough, the effects are demonstrable at lower doses near the site of uptake and metabolism Thus orallyadministered PAHs may induce skin tumours, they have been shown to induce tumours of the digestivetrack at lower doses The reverse is true when PAHs are applied to the skin (MOE 1997)

Some metals appear to be carcinogenic when inhaled Although they may have other toxic effects whenthey are taken up by another route, the evidence for carcinogenicity is either absent or not very strong.Most cancer ranking schemes do not provide separate ranking for each route of exposure, although someinformation may be provided in the text accompanying the ranking Table 4.1.2 presents the original ranking

by the three agencies for the selected contaminants For these substances, the carcinogenicity rankingdescribes well the health impact resulting from inhalation exposure but does not describe as well the impactresulting from oral exposure ToxProbe Inc approximated the ranking for oral exposure ToxProbe doesnot recommend using the ToxProbe ranking for oral exposure out of context from this document The onlypurpose of this exercise is to demonstrate the route-specific difference in the weight of evidence

classification for carcinogenicity A more thorough ranking exercise would be required for any otherpurpose.

In general, with the exception of tetrachloroethylene, there is a consensus that all the substances of interestare either classified as human carcinogens or probable human carcinogens by inhalation exposure Oralingestion is also a major concern for benzene, dioxins and PAHs

Table 4.1.2 Weight of evidence classification for carcinogenicity by inhalation route The weight of

evidence conclusion for other routes of exposure is sometimes different.

USEPA1), oral

human carcinogen

3 Priority Substances List Reports

4 not differentiated from inhalation

5 ToxProbe Inc interpretation based on material in

IRIS

6 for explanation see text

7 US EPA (1998a) draft reassessment considers

1,3-butadiene as a known human carcinogen.

8 USEPA (2000) classifies 2,3,7,8-TCDD as a human

carcinogen, but other 2,3,7,8-TCDD-like compounds

as “likely” human carcinogens All complex environmental mixtures of 2,3,7,8-TCDD and dioxin- like compounds are characterized as “likely’ human carcinogens The draft report is currently under review.

4.2 Genotoxicity

Some carcinogens are believed to induce cancer effect even at very minute doses, although the probability

of adverse effects at low doses is low There is no safe level of exposure for these chemicals As thelevel of exposure increases, so does the risk At low dose levels, the increase is linear This means that ifthe level of exposure increases by two-fold, the risk is also expected to increase proportionately two-fold These cancer-inducing compounds are referred as non-threshold carcinogens The mechanism by whichthey induce their effect requires a genotoxic event that results in an irreversible mutation in the DNA of a

somatic cell and is called initiation and the carcinogens acting by this mechanism are called initiators.

In contrast, some carcinogens are thought not to induce an adverse effect, until a certain minimal exposure(threshold exposure) is reached Above the threshold, the severity of the effect increases in proportion tothe exposure level These carcinogens are referred to as threshold carcinogens They are thought to inducecell proliferation and allow for clonal expansion of the initiated cells and a mutation is not required This step

is called promotion and the carcinogens acting by this mechanism are called promoters The next step in

the development of cancer is called progression and is thought to involve further genotoxic events

The carcinogens, which act by all the above mechanisms are called complete carcinogens It is outside

the scope of this report to provide a detailed review of the mechanism of carcinogenicity Good reviews areavailable from Farber (1987) and from Barrett and Wiseman (1987)

Since initiators must be able to trigger a mutagenic event while the same is not true for promoters, theabsence of mutagenic properties in a carcinogenic agent together with proven ability to induce cellproliferation is taken as evidence that the agent is a promoter Conversely, highly mutagenic agents aretreated as initiators The rating of evidence for mutagenicity of selected contaminants is listed in table 4.2.1.The comparative ranking of promoting properties of carcinogens is not available, but the evidence is goodfor asbestos, formaldehyde and benzo[a]pyrene Dioxins and similar compounds are not genotoxic Theyexert their carcinogenic action through binding to and subsequent activation of the Ah receptor

Initiators tend to be considered of greater concern with regards to environmental exposure This is becausethese carcinogens are expected to pose some (small) risk even at very low concentrations, such as thoseusually found in the environment In contrast, the level of exposure associated with cell proliferation tends

to be relatively higher Thus even though an exposure to promoters may have occurred, there may not beany adverse effect if the exposure is low enough This is why CEPA’s weight of evidence ranking schemetends to rank promoters lower than initiators (see above) In the occupational setting, where exposures tend

to be higher than environmental levels, promoters are more likely to pose a significant risk Furthermore,thresholds of some non-genotoxic carcinogens (dioxins, for example) can be quite low and exposure mayexceed the carcinogenic threshold in the environmental setting

In most cases, considering the non-threshold effects of a chemical rather than its threshold effects in therisk assessment process is a more conservative approach and is more protective of human health However, where the situation is uncertain, it is prudent to assess both threshold and non-threshold effects.Some agencies (USEPA and especially California Environmental Protection Agency) are particularlyconservative and use the non-threshold model to provide an additional margin of safety to their calculations

USEPA has been criticized for its policy of always assuming a non-threshold mechanism for carcinogens.This policy has now been revoked, and USEPA is now considering a wide range of data in its effort todetermine what is more appropriate, to assume a threshold or a non-threshold mechanism USEPAassessments seem to continue the use of the no threshold model even for non-mutagenic carcinogens.

As illustrated in table 4.2.1, most of the selected carcinogens are mutagenic and are considered initiators.The exceptions are dioxins, tri-and tetrachloroethylenes

Table 4.2.1 Mutagenicity evaluation

Evaluation by Agencies

mutagenic

1 IRIS database

2 WHO Air Guidelines for Europe

3 CEPA’s Priority Substances List Reports

4 Since the USEPA and WHO evaluations, there is increasing evidence strongly suggesting that asbestos

is genotoxic, causing damages to the chromosomes (ATSDR, 1995a) There is also evidence

indicating that asbestos could be mutagenic, causing large DNA deletions, which may not be easily detected (ATSDR, 1995a).

4.3 Types and sites of cancer encountered

Different carcinogens have a tendency to induce tumours at different sites and different cancers types.Table 4.3.1 below summarizes the site and the type of tumour induced by the selected contaminants Thelist is not necessarily complete and only the best-documented tumours are included in the table Note thatfor some contaminants, the site and the type of tumour depend on the route of exposure

Table 4.3.1 Sites and types of tumours

1,3-butadiene Cancer of lymphohaematopoietic system (leukemia,

lymphosarcoma and reticulum cell sarcoma)

ATSDR (1992)

Asbestos Lung cancer (cancer of the lung tissue itself) and

mesothelioma (a cancer of the thin membrane that surrounds the lung and other internal organs)

ATSDR (1995)

by proliferation of myeloid tissue in bone marrow and spleen and an abnormal increase in the number of white blood cells called granulocytes and cells which give rise

to myelocytes and myeloblasts in the circulating blood)

ATSDR (1997)

Dioxins Best human evidence is for all cancers combined, lung

cancer and soft tissue sarcoma, liver cancers in animals

USEPA (1994b)

ATSDR (1999)

Inhalation: mainly lung tumours Dermal: mainly skin tumours

ATSDR (1995d)

Trichloroethylene No consistent pattern as to the type of cancer CEPA (1993a)

4.4 Other effects

Examination of adverse health effects other than cancer for the selected contaminants falls outside thescope of this report However, it is important to bear in mind that the selected agents have other toxiceffects other than cancer and that these effects may play an important role in the overall toxicity of theagent The non-cancer effects may be particularly important in occupational settings, where exposures tend

to be higher than environmental exposures Table 4.4.1 provides a brief summary of the major toxic effects,other than cancer, of the selected agents

Table 4.4.1 Major toxic effects (other than cancer) of selected agents

1,3-Butadiene Cardiovascular, hematopoietic (blood formation),

reproductive and developmental effects, and respiratory diseases

ATSDR (1992)

Asbestos Asbestosis - scar-like tissue in the lungs and in the

membrane that surrounds the lungs

ATSDR (1995)

inhalation, oral, or dermal exposure; effects on red blood cells, white blood cells, platelets; bone marrow damage leading to aplastic anemia

ATSDR (1997)

Cadmium Kidney damage after oral or inhalation exposure; also

respiratory effects, but non-occupational exposure to cadmium is unlikely to be high enough to cause these effects; respiratory effects tend to be reversible with discontinuation of exposure

ATSDR (1993a)

Chromium (VI) By inhalation: nasal septum ulceration and perforation, and

other irritating respiratory effects, asthma

By dermal exposure: dermatitis, skin ulcers

By inhalation, oral, dermal: possible respiratory, cardiovascular effects, gastrointestinal and hematological effects, liver and kidney effects,

ATSDR (1993b)

Dioxins Chloracne, reproductive and developmental toxicity,

immunotoxicity

USEPA (1994b)

Formaldehyde Inhalation: upper respiratory tract irritation, dysplasia and

squamous metaplasia of the respiratory and olfactory epithelia

Oral: papillomas in the forestomach of rats Dermal: skin irritation at high doses

IPCS (1989a)

Tetrachloroethylene Acute effects: reversible neurological effects such as

headache, dizziness, nausea, difficulty in speaking, and sleepiness

Long-term: neurological and neurobehavioral effects, lung congestion, kidney effects, liver effects

ATSDR (1995c)

4.5 Carcinogenic potency

4.5.1 Threshold versus non-threshold dose-response effects

As discussed in section 4.2, many cancer-inducing compounds and some other toxicants are non-thresholdtoxicants There is no safe level for these chemicals As the level of exposure increases, so does the risk

At low dose levels, the increase is linear In contrast, most non-cancer inducing chemicals and somecarcinogens are thought not to induce an adverse effect, until a certain minimal exposure (thresholdexposure) is reached Above the threshold, the severity of the effect would increase as the exposure levelincreases For example, atropine will cause widening of the pupil at a certain concentration Below thatconcentration, atropine is thought to have no effect on the pupil These toxicants are referred to asthreshold toxicants

The distinction between threshold and non-threshold effects is needed, because the approach to assessingthe risk for the two groups of chemicals is different For chemicals with a threshold, the purpose of thedose-response assessment is to identify this threshold at which no adverse effect is expected Noobservable adverse effect level (NOAEL) or a benchmark dose is determined either experimentally or in ahuman epidemiological study For threshold toxicants, NOAEL is a measure of toxic potency The morepotent the threshold toxicant is, the lower the dose at which no adverse effect is detected By applying anappropriate safety factor that accounts for the uncertainties in the estimation of the threshold, the referencedose (RfD), which is also called tolerable daily intake (TDI), is determined

Since there is no “safe” level for non-threshold chemicals, it is necessary to establish a level of exposurefor each chemical that is deemed operationally as “tolerable” Such a level is called risk-specific dose(RsD)

“Tolerable” risk levels differ not only from chemical to chemical but also from organisation to organisation,circumstance to circumstance and they are often controversial What is tolerable depends usually on anindividual’s perspective Generally for environmental exposures, a tolerable risk has been operationallydefined as the probability of an adverse event ranging from one in 10,000 to one in a million Mostorganisations use RsDs at one in a million risk for human health This is the risk level that will be used inthis report

RsD is affected not only by the level of risk deemed tolerable, but also by the potency of the non-thresholdeffect of the toxicant Potency is generally expressed as the initial slope of the dose-response curve Thisslope estimates the increase in risk as exposure is incrementally increased The higher the potency, thegreater the increment of risk resulting from a given increment of exposure and the steeper the slope of thedose-response curve is The RsD is derived from this slope

The decision as to whether to treat an agent as a threshold or non-threshold toxicant often has a largeimpact on its potency estimate Non-threshold estimates tend to be far more conservative in manycircumstances

Potency Estimates

Carcinogenic potency by inhalation, oral and dermal routes is summarized in tables 4.5.1 and 4.5.2 In thecase of dioxins and PAHs, the cancer potency estimates developed by the four organisations differsignificantly These differences are discussed in section 4.5.1 and 4.5.2, as well as in appendix A The fouragencies listed in tables 4.5.1 and 4.5.2 have not developed a cancer potency for tetrachloroethylene(perchloroethylene) California Environmental Protection Agency (CalEPA) (1991), on the other hand,estimated a lifetime cancer unit risk of 8 x 10-3 (mg/m3)-1 for tetrachlorethylene The use of this estimate isnot recommended, given the many questions related to the carcinogenicity of this agent in humans (seesection 4.1) Some of these questions relate to the inadequacy of carcinogenic evidence in humans and therelevance of the mechanism of tumour induction in animals to humans

Most agencies do not develop cancer potencies for dermal exposure, although MOE (1997) did developdermal potencies for PAHs Procedures and uncertainties associated with estimating dermal potenciesfrom oral potencies are discussed in section 4.5.3 and the potency estimates are provided in table 4.5.2

As indicated in table 4.5.1, carcinogenic PAHs and chromium (VI) appear to be the most potentcarcinogens by inhalation exposure among the initiators, followed by asbestos and cadmium 1,3-butadieneand benzene are about 3 to 4 orders of magnitude less potent than PAHs and chromium (VI) Oral anddermal potency factors are available only for a few of the substances Other than inhalation, dermalexposure to carcinogenic PAHs is of great concern while oral exposure to PAHs is of lesser importance However, these comparisons are done without taking into consideration the weight of evidence supportingthe identification of a chemical as a carcinogen For example, while benzene is classified as a humancarcinogen, PAHs are probably carcinogenic to humans The orders could have been different if theweight of evidence classification could be factored into the comparison

Among substances (e.g dioxins and related compounds, trichloroethylene and tetrachloroethylene) forwhich the evidence for mutagenicity is weak, i.e their potentials for initiation are low, dioxins and relatedcompounds are likely the most potent carcinogens However, it is difficult to compare dioxins and relatedcompounds against the other substances Dioxins and related compounds are promoters whereas the othersubstances are tumour initiators Some are complete carcinogens, such as B[a]P Since the action of apromoter requires prior tumour initiation, an adverse effect may not occur ensuing exposure to a promoter,especially if the level of exposure is low In contrast, initiators are expected to pose some (small) risk even

at very low concentrations As a result, promoters tend to be considered of lesser concern than initiatorswith regards to environmental exposure On the other hand, dioxins and related compounds are very potent

as promoters The levels at which dioxins and related compounds likely exert their tumour promotionproperties are lower than the levels at which other substances start to significantly initiate tumour formation(i.e levels associated with an added cancer risk of one in a million for initiators) This is true for all routes

of exposure

Table 4.5.1 Inhalation Potency of selected carcinogens, expressed as unit risks (µg/m 3 ) -1 except for

asbestos (fibres/mL) -1 The recommended values are in bold face.

Sources MOE (1) USEPA (2) WHO (3) CEPA (4)

Dioxins No values given here Issues are too complex to be summarized in a table.

Please refer to section 4.5.1.

-USEPA (1991) draft Formaldehyde Risk Assessment Update.

B[a]Ps represents a potency of a PAH-rich mixture, where the concentration or dose is expressed in terms of

benzo[a]pyrene (B[a]P) content.

Table 4.5.2 Oral and dermal potencies of selected carcinogens expressed as slope factors (mg/kg

day) -1 The recommended values are in bold face.

Sources MOE oral (1) USEPA oral(2) CEPA oral(3) Dermal

-Derived from oral potency See section 4.5.3 for details

B[a]Ps represents the potency of a PAH-rich mixture, where the concentration or dose is

expressed in terms of benzo[a]pyrene (B[a]P) content.

4.5.2 Estimating potency for dioxins

Assessment of the toxicity of polychlorinated dibenzo-p-dioxin (dioxin)/polychlorinated dibenzofuran(furan)/coplanar polychlorinated biphenyl (PCB) mixtures is usually conducted using toxic equivalencyfactors (TEFs) The concept of toxic equivalence is based on a common mechanism of action within thisclass of compounds (for listing of these compounds and their TEF values, see appendix B) TEFs areassigned to individual dioxins, furans and coplanar PCBs on the basis of how toxic they are in comparisonwith the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), the most potent dioxin Thisapproach first estimates the potency of TCDD and then expresses the environmental levels of other dioxin-

like compounds as “TCDD equivalents” (TEQs) In order to estimate the toxicity of a mixture of

dioxin-like compounds, the total number of TCDD equivalents in the mixture is multiplied by the potency ofTCDD The result is numerically equivalent to summing up the risks attributable to individual dioxin-likecompounds in the mixture

Potency of TCDD

Although dioxin-like compounds induce a wide range of effects, the dose-response assessments conducted

by major regulatory agencies focus on cancer as the endpoint However, there are major differences in theway these organisations establish the dose-response relationship and this difference has a major effect onthe estimates of toxicity

In the case of dioxin-like compounds, there is no consensus on whether to treat this family of compounds asthreshold or non-threshold carcinogens However, the arguments are complex and beyond the scope of thisreport It should be noted that while US EPA (1994b, 1997a, 2000) assessed the potency of TCDD andthus of all the other compounds for which TEFs are developed as non-threshold carcinogens, WHO(1995b) and CEPA (1993c) treated these compounds as threshold carcinogens This is probably the mainreason for the large discrepancy among the exposure limits derived by the three agencies (see below forfurther details)

US EPA (2000)

US EPA (2000) assumed a non-threshold dose-effect relationship for dioxin-like substances It conducted

its dose-response assessment using three occupational studies (Fingerhut et al 1991; Manz et al 1991; Zober et al 1990) The human data suggest an ED01 (effective dose resulting in 1% excess risk) based on

the average lifetime body burden in the range of 6-80 ng/kg for all cancers combined and 36-250 ng/kg forlung cancer These estimates correspond to upper bound slope factors of 8.6 x 10-3 to 2.5 x 10-4 risk per pgTCDD/kg/day Since there is no a priori reason to choose one specific study over the other, US EPAperformed a meta-analysis by combining all data sets into a single large data set yielding a slope factor ofapproximately 1 x 10-3 per pg TCDD/kg/day This value represents US EPA’s most current upper boundcancer slope factor for estimating human cancer risk based on human data The slope factor derived fromanimal data supports this estimate

WHO (1995b)

WHO implicitly assumed a threshold for the effects of TCDD-like substances and developed a tolerabledaily intake (TDI) of 10 pg/kg/day based on TCDD-induced liver cancer in rats, for which the NOAELwas 1000 pg/kg/day 1000 pg/kg/day corresponds to 540 ng (10-9g) of TCDD/kg of liver wet weight in rats

In humans, such TCDD content in the liver is estimated to require an intake of 100 pg/kg/day of TCDD.The TDI is derived from this value by applying an uncertainty factor of 10 This factor is intended toaccount for the different sensitivity among individuals to TCDD

In 1998, WHO revisited its risk assessment for dioxin and dioxin-like compounds A TDI of 1 - 4 TEQpg/kg/day was established for dioxins and dioxin-like compounds based on dioxin-induced developmentaland reproductive effects in rats and monkeys Lowest Adverse Effect Levels (LOAEL) ranging from 14

to 37 pg TCDD/kg/day were identified from a series of developmental and reproductive studies These

studies observed a decrease in sperm count, immune suppression and an increase in genital malformation in

the offspring of exposed rats (Gray et al 1997a, Gray et al 1997b, Gehrs et al 1997, Gehrs & Smailowicz,

1998) Endometriosis was observed in exposed monkeys in one study (Rier et al 1993) while

neurobehavioral effects were identified in the offspring of exposed monkeys in another study (Schantz andBoman, 1989) An uncertainty factor of 10 was applied to the LOAEL to arrive at the TDI This factoraccounts for the use of a range of LOAELs instead of a NOAEL, the possible differences in susceptibility

to these compounds between humans and experimental animals, the potential differences in sensitivitywithin the human population and differences in half-lives of elimination for the compounds of a complexTEQ mixture WHO assessment suggests that developmental effects may be more important thancarcinogenic effects for dioxin and dioxin-like compounds

At the proof review stage of this draft, the Science Advisory Report released a draft report (SAB, 2001)which recommends against reliance on the exclusive use of non-threshold extrapolation That draft offers

an excellent discussion of the issues involved

4.5.3 Estimating potency for PAHs

PAHs exist in the environment as a mixture and not as single compounds As a result, all the availablehuman toxicological data involve mixtures, rather than individual compounds Quantitative experimental dataare available for only a few of these compounds Furthermore, only a few PAHs are on the routinemonitoring lists A risk assessment based on the few well-characterized PAHs is therefore likely tounderestimate the risk from the entire PAH family by more than a hundred fold (For discussion andreferences, see MOE 1997)

The cancer risk due to a complex mixture of PAHs can be estimated by conducting a risk assessment onindividual PAH, and the risk attributable to each selected PAH in the mixture can be added up to form anaggregate risk Alternatively the toxicity of the complex mixture can be expressed in terms of the potency

of a single “standard” compound with well-quantified potency Such an expression of relative potency iscalled toxicity equivalent factor (TEF) The potency of the mixture is then estimated as the product of thenumber of TEFs and the potency of the “standard” compound on which the TEF is based The twoalternatives are numerically identical This approach has been used to develop USEPA drinking water(USEPA, 1993a) and CEPA’s air guidelines (CEPA, 1994b)

An alternative approach is to assess the carcinogenicity of the PAH fraction of the mixture as a whole The quantity of PAH in the mixture and the potency of the mixture is estimated from the quantity of a

“surrogate”, B[a]P in this case It is therefore assumed that as the levels of B[a]P increase, so will thelevels of other cancer-causing PAH and the potency of the mixture In this approach, B[a]P is assignednot just its own potency, but the potency estimated for the whole PAH fraction Although it has beenshown that PAH profile differs depending on the source of emissions and the conditions of combustion,these differences are not sufficiently large to alter the outcome of the risk assessment (MOE, 1997) WHO(1996) and MOE (1997) have adopted this approach The differences between CEPA’s potency estimatesand the WHO and MOE estimates are partly due to the fact that the CEPA assessment assigned B[a]Ponly its own potency, while WHO and MOE assessments assigned B[a]P not only its own potency but thepotency of the whole PAH fraction WHO and MOE estimates differ by about an order of magnitude Their values differ because the MOE estimate was based on the initial slope representing the best fit of thelinearised multistage model to the data, while WHO used a more conservative 95% upper confidence limit(UCL) on that slope MOE (1997) has also provided the UCL potency estimates The difference in theoral potency estimate for B[a]P stems from the fact that MOE has extrapolated the oral cancer potencyfrom human inhalation data, while CEPA has used the animal ingestion data as the starting point In arriving

at its approach, MOE (1997) has compared the two different sets of extrapolations and concluded that theroute-to-route extrapolation it used is associated with a lower level of uncertainty Please refer to Appendix

A for further discussion

4.5.4 Estimating Dermal potency from Oral Potency

USEPA (1996b) has demonstrated that extrapolation of exposure limits from oral to inhalation exposuremay lead to a significant underestimation of the risk Although no similar evaluation is possible forextrapolation from oral to dermal exposure, the possibility that the same result may hold true exists

The use of oral dose response parameters, such as RfD or cancer slope factor, as dermal dose responseparameters, after correcting for incomplete absorption by dermal exposure, is currently a common practice This practice implicitly assumes that the health effects elicited are related only to the total uptake and arenot dependent on the route of exposure This assumption may hold for some chemicals, such as lead anddioxins Some other substances tend to have different potencies and act at different organ sites depending

on the route of exposure PAHs are good examples (MOE, 1997) They are activated to a significantextent by metabolism in the skin following dermal absorption before being delivered to the liver wheremetabolism of most xenobiotics takes place Some substances may cause skin irritation, a phenomenon that

is not normally taken into consideration in developing an oral exposure limit These factors make dermalexposure significantly different from oral exposure As a result, the use of oral dose response parameters inevaluating health risk from dermal exposure may significantly underestimate the risk (for example nickel,chromium VI)

USEPA (1989a, 1992b, 1998c) discusses another important issue: oral and dermal RfDs and slope factorsare developed and used differently Oral dose response parameters are usually developed in terms of theadministered dose, rather than the delivered or absorbed dose The administered dose represents the totalintake of the test substance, not corrected for absorption In contrast, the delivered or absorbed dose is theadministered dose that has been corrected for uptake The vehicle in which the test substance is delivered

is usually selected to minimally impede uptake When an oral RfD or a slope factor is applied to anenvironmental situation, the actual absorption may be less complete compared to the experimentalconditions, making the application of the uncorrected slope factor conservative For example, absorptionfrom the soil matrix may be less than absorption from a solution matrix administered by gavage in thelaboratory The oral slope factor when applied as a substitute for a dermal slope factor is usually correctedfor bioavailability by assuming a 100% uptake In effect, the administered dose is assumed to be equal tothe absorbed dose On the other hand, dermal exposure is usually described in terms of absorbed dose These practices lead to an underestimation of the dermal uptake due to over-correction for oralbioavailability; the magnitude of the underestimation being inversely proportional to the true oral absorption

of the chemical in question The USEPA (1989a, 1992b) therefore recommends correcting the oral slopefactor for bioavailability before extrapolation to dermal toxicity values, if defensible data allow for such acorrection If correction for bioavailability is impractical, the USEPA (1992b, page 10-10) recommends

conducting route-to-route extrapolation from oral to dermal toxicity values only when accompanied with a strong statement emphasizing the uncertainty involved.

Following the USEPA assessment of bioavailability by dermal route for a number of substances in 1992, theUSEPA regions (1995, 1998c) started to compile guidance on skin absorption factors for the SuperfundProgram This report makes use of the skin absorption factors recommended by Risk AssessmentInformation System (RAIS, 2000) RAIS provides estimates of absorption factors for both the dermal andthe oral routes The availability of oral absorption factors allows for the conversion of oral potencyexpressed in the form of administered dose to the form of absorbed dose The availability of dermalabsorption factors allows for calculation of dermal absorbed dose using the oral absorbed dose Theextrapolation of dermal RfD from the oral RfD is illustrated below

RfDdermal = RfDoral x (foral / fdermal)

Derivation of dermal slope factor from oral slope factor can be achieved using the equation below

Slopedermal = Slopeoral x (fdermal) / foral)

The results are summarized in table 4.5.2 As discussed above, oral to dermal extrapolation does not takeinto account effects, which are observed only when individuals are exposed via the dermal route Thepotencies for these dermal effects are generally not available and it is therefore important to recognize thatthis assessment may underestimate the level of health concern by dermal route of exposure

5 Occupational exposure

workers

Few attempts have been made to establish comprehensive estimates of occupational exposure to

carcinogens IARC has been publishing IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans on individual carcinogens, groups of carcinogens, carcinogenic mixtures,

and industries linked with elevated incidence of cancer since 1972 Over the decades, IARC has assembled

an impressive and highly respected overview of exposure to carcinogens in the workplace InternationalProgramme on Chemical Safety (IPCS) is another useful source of information and has been publishingEnvironmental Health Criteria (EHCs) since 1976 EHCs have a broader scope than IARC and tend tofocus on environmental issues, but occupational exposure is also included

Although the IARC and IPCS reports are of high quality with extensive input from senior scientists andtake considerable effort to prepare, the older issues would not have information about recent exposures Industrial processes have changed over the years and steps have been put in place to protect workers’health The older data probably do not reflect current situations and likely overestimate recent occupationalexposures In addition, both IARC and IPCS reports contain exposure information for specific occupationsgathered from different sources The methodologies used to gather the data and the data structure may notalways be comparable, making it very difficult to compare exposures between different industrial sectors

At one time, the Ontario Ministry of Labour (MOL) used to systematically collect exposure information onchemical and physical agents in the workplace, but that is not currently being done The older data arebeing transferred into a new database and until this database is operational, the occupational exposure dataare not available (McCloskey, 2001) Although some data may be available from MOL and from someother organisations in the future, a comprehensive database containing exposure information to occupationalcarcinogens is currently not available It is noteworthy that Cancer Care Ontario has identified thecollection of occupational exposure information as a top priority

In principle, there are three possible general approaches to building an occupational exposure database First, it is possible to integrate and standardise the existing occupational exposure data for Toronto workersfrom different sources Such an approach would be labour-intensive and one would likely accomplish onlypartial success in data standardization It is expected that such a database would have numerous gaps,which would need to be filled

A second alternative would be to sponsor a major monitoring/survey study involving many industrial sectors

to create a standardised database, perhaps similar to the environmental emission inventories [e.g NationalPollutant Release Inventory (NPRI - see http://www.ec.gc.ca/pdb/npri/ ), Toxics Release Inventory (TRI –