An evaluation of the plausibility that exposure to certain

Pesticides as plausible cause of the Bellarine Penisula cancer cluster Prof BW Stewart

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An evaluation of the plausibility that exposure to certain pesticides may account for the Bellarine Peninsula cancer

cluster

Professor Bernard W. Stewart AM MSc (UNSW), PhD (Lond), FRACI, DipLaw (LPAB), DipLegalPract (NSWCollLaw)

School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, Sydney

Contents

Summary 2 Introduction 3 Dieldrin (and Aldrin) 6 DDT 9 Organochlorine pesticides generally 13 Malathion 15 Chemicals possibly used for mosquito spraying 17 Inferences from cancer attributable to point source pollution 19 Conclusion 22 Appendix 1. Investigations of highly publicised cancer clusters 24 Appendix 2. Cancer clusters as contributing to the discovery of carcinogens 28 Appendix 3. WHO carcinogen evaluation procedures 31 References 33

Investigations into a possible cancer cluster on the Bellarine Peninsula, VictoriaSubmission 35


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Summary

One aspect of any cancer cluster investigation is whether increased incidence of cancer has

occurred. The other aspect of any cancer cluster investigation, and the subject of this report,

is whether cancer in the population identified by the cluster report is attributable to a

particular agent(s).

With reference to pesticides implicated as potential causes of the multiple types of

malignancy which constitute the Bellarine Peninsula cancer cluster, an assessment of their

carcinogenicity (ability of cause cancer) in humans is provided in this report.

Three of the pesticides identified as being of concern, namely dieldrin, DDT and malathion,

are categorized by WHO as probably carcinogenic to humans. Data concerning circumstances

of known exposure to each of these pesticides and evidence that one or more types of cancer

may be caused by each of them, has been summarized. None of these pesticides may be

reasonably implicated as causing the cancer cases under consideration, particularly in light of

relevant circumstances of exposure.

Where possible, reference is also made in the report to exposure and carcinogenicity data

concerning pesticides or categories of pesticides not subject to WHO evaluation. No relevant

insight was gained. Examination was also made of findings following investigation of

circumstances that could be likened at least one respect to the present cluster. This review

confirmed that no closely similar situation of likely cancer causation under circumstances like

those characterizing the Bellarine Peninsula cancer cluster has been reported in the medico-

scientific literature.

In light of all the available evidence, causation of multiple tumour types specified in relation

to the Bellarine Peninsula cancer cluster by exposure to pesticides specifically as these

chemicals are present in soil as a result of earlier usage, is not plausible. The pesticides DDT

and dieldrin are the chemicals for which most relevant information is available, but neither of

these can be specified as a plausible cause of this cancer cluster. The possibility that

causation has occurred cannot be excluded with absolute certainty: a scenario which applies

to all investigations of this type.

Relevant background information is provided in three Appendices which cover investigations

of highly publicised cancer clusters, cancer clusters as contributing to the discovery of

carcinogens and WHO carcinogen evaluation procedures



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Introduction

As fully explained immediately below, investigation of a cancer cluster involves two

considerations: whether there has been a more-than-expected number of cancer cases in a

particular sub-population and whether this subpopulation has been exposed to a carcinogen(s)

in circumstances leading to cancer development. Succinctly expressed, the consideration of

risk and of exposure. In that context, this report is concerned with exposure.

This introduction outlines what is recognized as a cancer cluster, the recognition of both risk

and exposure as aspects of any cancer cluster investigation, and the nature and management

of scientific data concerning the cancer causation in humans by chemicals. All such

information is oriented with reference to pesticides, and particularly those pesticides

identified as relevant to the Bellarine Peninsula cancer cluster.

The five sections following are concerned with particular pesticides or groups of pesticides.

In each such section, available data concerning circumstances of exposure and the

carcinogenic potential for each chemical or group of chemicals are specified and relevance to

the Bellarine Peninsula cancer cluster is assessed. Scientific documentation of increased

community cancer thought to be attributable to various pollutants including pesticides is

reviewed in the penultimate section. On the basis of all thus reported, the plausibility that

pesticide exposure played a role of the Bellarine Peninsula cancer cluster is assessed.

Certain background information is provided in three appendices. I have been involved as a

committee member in multiple cancer cluster investigations undertaken by NSW Health (the

Port Kembla leukaemia cluster, the Mono Vale childhood cancer cluster and the Helensburgh

lymphoma cluster among others) as well as double that number investigated through the

South East Sydney Public Health Unit. In all such investigations, final authority rested with

cancer professionals proficient in epidemiology and carcinogenesis. The information

contained in three appendices would be, in the main, common knowledge to such

professionals. For the present, this same background information may not be otherwise

presented in the present context and is not available at a single source.

What is a cancer cluster?

A cancer cluster is an increase in the expected number of cancer cases in a particular

community during a specific period which is reported to health authorities.

This definition, which was adopted by US authorities [1], is helpful, but not the whole story.

Key to the reporting of a cluster to health authorities is recognition, by the community

affected, that increased incidence of cancer has occurred. An increased incidence of cancer

may be self-evident. A higher-than-expected incidence of bowel or breast cancer in particular

families is often recognized by family members and subsequently confirmed by specialists in

familial cancer clinics. In the wider communities, ABC employees working in Brisbane

recognized for themselves that a higher than expected number of breast cancer cases had

occurred, and this was later shown to be a 6-fold increase.

However, since cancer is never uniformly distributed across the population, particular sub-

populations must variously exhibit higher or lower incidences of cancer. Sub-populations

exhibiting increased incidences of cancer are evident from population-based epidemiological



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data, but such variations from average are never termed ‘clusters’. They are not reported to

health authorities because they are identified by health authorities.

Lower incidences of cancer are almost never investigated. Likewise, increased incidences of

cancer due to chance are neither a matter of concern nor do they identify an opportunity to

avoid such an occurrence happening elsewhere. Central to community concern about cancer

clusters is the increased incidence of cancer identified is due to a causative agent(s).

Beyond an increased number of cancer cases, a central issue in the reporting of a cancer

cluster to health authorities is causation. The nature of a likely causative agent may be self-

evident from the circumstances of the cluster. Thus the ABC breast cancer cluster

immediately implicates electromagnetic fields associated with broadcasting as a likely cause.

Evidence of local pollution may be understood as causative as exemplified by chromium-6-

contamination of water being recognized as the cause of cancer in Hinkley CA as

documented in the film ‘Erin Brockovich’. Information about the ABC, Hinkley and other

cancer clusters is given in Appendix 1. In the absence of an evident circumstance of

exposure, the community may rely on health authorities to determine the cause of a particular

cluster. Whether recognized by, or unknown to the community affected, assessment of

carcinogen exposure is central to any cancer cluster investigation. This report addresses that

matter in relation to the Bellarine Peninsula cancer cluster

How are cancer clusters investigated?

Investigation of cancer clusters involves the two matters identified above: increased

incidence and plausible causation. In the past at least, the dominant focus of cancer cluster

investigations has been establishing that increased incidence of cancer has occurred. Lesser

attention has been given to determining plausible causation. In point of fact, equal attention

should be paid to both these matters, and some scientific thought favours the latter as the first

priority [2].

The first public hearing in relation to the Bellarine Peninsula cancer cluster paid close

attention to the matter of increased incidence of cancer in the relevant community by

comparison with that of the entire population of Victoria. As separate from that matter, this

report is made with reference to plausibility. Was the population exposed to an agent(s) the

carcinogenicity (cancer-causing potential) of which would account for the cluster?

In notifying the Bellarine Peninsula cancer cluster to health authorities, the impact of

pesticides previously used in the region was specified as the immediate explanation. For the

purpose of investigation, this matter of causative agents has been specified as follows

The public hearing is designed to gather evidence from scientific experts in relation to:

The chemicals previously used for agricultural purposes on the Bellarine Peninsula;

o In particular: deildrin, DDT, and organochlorine pesticides generally.

The chemicals possibly being used for mosquito spraying on the Bellarine Peninsula;

o In particular: temephos, malathion, fenthion, synthetic pyrethrums, and

organophosphorus pesticides generally.

The likelihood that exposure to these chemicals could cause cancer in humans;

o Information on what level of exposure might have an effect on humans;

o Information on whether exposure could lead to different types of cancers

becoming more prevalent (or whether the same type of cancer is more likely);



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The avenue of enquiry described above is scientifically articulate and procedurally correct.

The specific chemicals mentioned and the terminology used allows for the immediate

documentation of relevant scientific data and its evaluation.

Investigating chemicals thought to cause human cancer

Evidence that a chemical may cause cancer in humans involves reference to findings from

epidemiology (evidence that the chemical causes cancer in humans), bioassay in rodents

(evidence that the chemical causes cancer in animals) and laboratory studies indicating

relevant biological processes (mechanistic evidence). An ideal situation is one in which

evidence of all three types just mentioned is available and consistent. Typically,

investigations of carcinogenicity are constrained because evidence of one or more types is not

available.

Epidemiological investigation of whether a chemical may cause cancer in humans often, but

not always, depends of identifying a particular circumstance of exposure. Typically, attempts

to detect increased incidence of cancer attributable to a particular chemical(s) involves a sub-

population or category of persons recognized to be highly exposed to that chemical. In

particular, people may be highly exposed to a pesticide as a result of working in its

manufacture or its application.

Amongst people exposed to a chemical or mixture of chemicals that causes cancer, a small

minority develop cancer, even when reference is made to those known to have the highest

level of exposure. ‘Only’ 16% of male lifelong smokers develop lung cancer. Risk of

developing cancer decreases as level of exposure decreases, and readily reaches the point

when, using current epidemiological methods, distinction cannot be made between absence of

increased incidence and increased incidence at a level which is so low that it cannot be

detected.

Way beyond those situations amenable to epidemiological study, levels of exposure to a

particular chemical may involve many scenarios. The chemical, even in trace amounts, may

be detected in food, consumer products, and/or as a pollutant in air, water and soil. Almost

invariably, direct evidence of a change in cancer incidence consequent each of the known

circumstances of exposure is not available because relevant studies cannot be justified given

the likelihood of failing to detect any effect.

Reliance on IARC evaluations where available

Documentation by me or anyone else of all available data concerning circumstances of

exposure and carcinogenicity for each of the pesticides identified in the present context is not

practicable: literally thousands of relevant medico-scientific investigations have been

published. Moreover, any individual may consciously or otherwise, cite those publications

which favour a particular conclusion.

To avoid these limitations the present report relies on determinations published by WHO as

‘IARC Monographs on the Evaluation of Carcinogenic Risks to Humans’. IARC refers to the

International Agency for Research on Cancer. The IARC Monographs are the most

authoritative determinations of carcinogenicity for particular chemicals, chemical mixtures

and workplace exposure currently available.



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All available data are addressed in the course of each evaluation undertaken by IARC, so

there can be no possibility of attention being paid to ‘selected’ data or investigations. Some

details concerning IARC Monographs are given in Appendix 3

For dieldrin, DDT and malathion, recent (2017-19) ARC evaluations are available

Information about each of these pesticides in the following sections is wholly based on

corresponding the IARC Monograph. Each of the Monographs so cited provides specific

references if any information presented in this report is to be further assessed.

Dieldrin (and Aldrin) The following is based on the IARC evaluation of dieldrin and aldrin published in 2019 [3]

Aldrin and dieldrin are synthetic organochlorine pesticides that act as contact and ingested

poisons for insects. They have been used to control infestations of pests such as ants and

termites, and to control several insect vectors of disease.

Aldrin and dieldrin are classified as persistent organic pollutants under the Stockholm

Convention. Their use in several countries including Australia has been banned or severely

restricted since the early 1970s.

Epidemiological data on aldrin were inadequate (italics in the IARC Monograph; for

explanation, see Appendix 3) and mechanistic data were sparse. However, since aldrin

rapidly converts to dieldrin in the body, exposure to aldrin inevitably entails internal exposure

to dieldrin.

Exposure

Despite bans in the early 1970s, use of these two compounds for specific purposes, including

as a termiticide and for vector control, continued up to the 1980s and 1990s, by which time

complete bans were in operation.

Occupational exposure to aldrin and dieldrin has been measured in aldrin- and dieldrin-

manufacturing workers, agricultural workers, and pesticide-treatment workers. The highest

concentrations of dieldrin were observed in insecticide-plant workers in the USA, with mean

serum concentrations in aldrin formulators of aldrin, 29.5 μg/L, and dieldrin, 182.5 μg/L.

Pesticide-treatment workers had median dieldrin serum concentrations ranging from < 1 to16

μg/L in several studies.

The general population can be exposed to dieldrin and aldrin directly from residues on food,

from living near areas where dieldrin or aldrin was sprayed, or from (past) use of aldrin or

dieldrin for insecticide treatments in and around the home.

Past use of aldrin and dieldrin has resulted in the presence of residues of these compounds in

the soil today. Both compounds bind to soil and are absorbed into the food chain. Sunlight



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and bacteria change aldrin to dieldrin. Dieldrin has low volatility and its half-life in soil has

been estimated to range from 2.6 to 12.5 years

Dieldrin and aldrin do not dissolve easily in water. Water concentrations are usually < 0.01 μg/L,

with higher levels attributed to contamination from industrial effluents and soil erosion during

agricultural use. Detectable concentrations of dieldrin are regularly reported in samples collected

5–15 years after use of dieldrin and aldrin was discontinued.

In the 1980s, dieldrin was detected in surface- and groundwater samples from Canada, from

Puerto Rico, and from 48 states of the USA. In a similar survey in the USA in1992–2001,

dieldrin was found in less than 5% of samples of stream water and ground water, but most

frequently and at the highest concentrations in areas where corn crops had been treated exten-

sively with aldrin and dieldrin

The highest levels of dieldrin serum concentration in the general population in the USA has

decreased by 10 times between 1976–1980 and 2001–2004. In measurements from the 1980s

until the 2010s in various countries, mean dieldrin concentrations were ~0.5–2 μg/L in blood,

2–5 ng/g lipid in breast milk, and 17–40 ng/g lipid in adipose tissue.

Evidence of carcinogenicity in humans Breast cancer is the primary consideration. In pesticide applicators and their families upon

which the US Agricultural Health Study (AHS) is based, risk of breast cancer in wives of

pesticide licensees was statistically significantly doubled if the husband had ever used

dieldrin. A Danish study nested case–control studies found a doubling in breast cancer risk

for the highest exposure group, with a strong dose–response relationship limited to subjects

with estrogen-receptor-negative tumours. A similar Norwegian study found no increase in

risk (but had fewer cases). The US case–control study of breast cancer found risk to be

increased, though not statistically-significantly, for the highest exposure grouping based on

serum dieldrin concentration measured at diagnosis.

In two US studies, no increase in risk of non-Hodgkin lymphoma was correlated with serum

dieldrin concentration whether measured at diagnosis or at enrolment in the study. In another

US study that used stored adipose tissue, the highest quartile of dieldrin concentration was

significantly associated with an increased risk of non-Hodgkin lymphoma. In questionnaire

studies, the AHS cohort study reported that ever use of dieldrin was not associated with an

increase in non-Hodgkin lymphoma or in any non-Hodgkin lymphoma subtype, including

multiple myeloma. A case–control study in the midwest USA found an elevated risk of non-

Hodgkin lymphoma associated with dieldrin use, although the effect estimate was not

statistically significant.

For leukaemia, the AHS found a non-statistically significant increase in risk for ever use of

dieldrin, while an older case–control study found no increase in risk. Dieldrin exposure was

not associated with prostate cancer (two studies) or colorectal cancer (two studies). Lung

cancer risk was increased with dieldrin use in the AHS, but not in a Dutch cohort study. Only

one study was available for cancer of the bladder, melanoma, or for cancer of the pancreas,

and no associations with dieldrin were reported.



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Evidence of carcinogenicity in animals There was sufficient evidence in experimental animals for the carcinogenicity of aldrin, with

three studies reporting the induction of hepatocellular carcinomas (liver cancer).

There was sufficient evidence in experimental animals for the carcinogenicity of dieldrin, as

hepatocellular carcinoma was observed in male and female mice in most of the 15 available

studies.

IARC evaluation

Dieldrin, and aldrin metabolised to dieldrin, is probably carcinogenic to humans (Group 2A).

The IARC Working Group considered that there was evidence for an association between

dieldrin and breast cancer, but that chance, bias, and confounding as accounting for the

association could not be ruled out.

There is limited evidence in humans for the carcinogenicity of dieldrin. A positive association

has been observed between dieldrin and cancer of the breast.

Broad perspectives

Exposure. Highest human exposure to dieldrin occurs amongst people employed in its

manufacture and those involved in its application, specifically in agriculture.

Dieldrin is recognized as a persistent pollutant Extensive use in agriculture means that

dieldrin may be anticipated to be detectable in soil from any area in high-income countries

(Northern American, Western Europe and Australia).

Amongst residents of high income countries, current exposure to dieldrin is mainly as a result

of diet, specifically from vegetation cultivated on dieldrin-contaminated soil. Consistent with

such intake, dieldrin may be detected in some meat samples.

Pollution by dieldrin is contrary to accepted public health principles. Levels in soil and

elsewhere have been falling since the pesticide was banned in the 1970s (on the basis of

carcinogenicity in experimental animals).

Statutory maximum levels for dieldrin in meat are subject to international agreements. Such

levels should not be exceeded as a matter of good health practice and statutory compliance.

Such levels are set at several orders of magnitude below those levels determined to cause

adverse effects in experimental animals.

Carcinogenicity. There is strong, but not definitive evidence that dieldrin may cause cancer

in humans. The evidence concerns particular tumour types; there is no evidence that dieldrin

may increase the incidence of all tumour types.

Evidence that dieldrin may be classified as probably causing (female) breast cancer primarily

implicates high exposure as a result of handling dieldrin in the course of its application in

agricultural work. In terms of the IARC evaluation, such occupational exposure to dieldrin

has not been associated with non-Hodgkin lymphoma specifically, other types of lymphoma

or leukaemia or any other specific malignancy.



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Associations between risk of breast cancer and blood levels of dieldrin have been

demonstrated, but causality has not be definitively established.

Although in the general US population, dieldrin is detectable in blood, there is no recognition

of a burden of any particular tumour type, including breast cancer, consequent upon the

general population being exposed to dieldrin.

Relevance to the Bellarine Peninsula cancer cluster

Exposure The presence of dieldrin in soil from the Bellarine Peninsula is consistent with

what would be expected worldwide and throughout Australia. There appears to be no

evidence of circumstances such as a previous site of dieldrin production for excessively high

levels of dieldrin to be anticipated in the Bellarine Peninsula region by comparison with

many neighourhoods worldwide, specifically in USA

Carcinogenicity In relation to the Bellarine Peninsular cluster, the specific cancers of interest

are breast, liver, non-Hodgkin lymphoma, multiple myeloma, brain cancers and leukaemia. Apart from breast cancer, none of these tumour types warrant discussion in respect of non-

occupational exposure to dieldrin. There is no body of evidence to support such a scenario.

Concerning breast cancer, present searching has not revealed a single study suggesting

increased risk attributable to residence on land previously used for agriculture. Presumably if

such a risk were to be explored, it would primarily involve people whose diet in large part

involved food produced on such land.

Apart from the absence of directly-relevant studies, in the literature concerning non-

occupational exposure to dieldrin, no speculation or acknowledgement of the need for

research concerning residents or others occupying or using facilities on former agricultural

land has been evident. In the US, huge areas of former agricultural land have been occupied

as cities in the ‘great plains’ States have expanded. Conventional epidemiology has not

implied a pesticide-associated increase in cancer risk. The hypothesis that such a risk from

dieldrin exists and is so great that it was self-evident in Bellarine Peninsula, Victoria,

Australia is not supported by available data.

DDT

The following is based on the IARC evaluation of DDT published in 2017 [4]

DDT is the universally-used acronym for the original, and now historic chemical name:

dichlorodiphenyltrichloroethane. The correct chemical name for DDT is 1,1ʹ-(2,2,2-

trichloro-ethylidene)bis(4-chlorobenzene).

DDT is recognized as mediating the elimination of malaria, the disease acknowledged for

many decades as the major preventable cause of death of humankind. DDT continues to be

used for this purpose in parts of Africa and Asia. The technical term for DDT when used to

prevent malaria by killing mosquitoes is ‘vector control’.



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From the discovery of its insecticidal properties in 1939 until its production and use began to

be phased out in many countries including Australia in the early 1970s, DDT was used

extensively for insect control in public health and agriculture worldwide. An estimated 1.8

million tonnes of DDT have been produced globally since the 1940s. Historically, DDT was

released to the environment during its production, formulation, and extensive use as a

pesticide in agriculture and malaria-control applications.

The Stockholm Convention on Persistent Organic Pollutants, signed in 2001, provided

initially for the elimination of 12 chemicals, one of which was DDT.

Exposure

Agricultural workers who have used DDT in various countries have blood levels of the main

DDT metabolite (that is, biological breakdown product, the most prominent of which is 1,1-

dichloro-2,2-bis(p-chlorophenyl) ethylene, usually abbreviated to DDE) of 10 ng/ml or

greater. Blood levels in people spraying DDT for malaria control may be much higher. Direct

comparison with blood levels in the general population is not possible because of the

complexity of DDT metabolism and the multiple DDT metabolites used in relevant studies.

DDT and its metabolites have been detected in air, rain, soil, glaciers, water, animal and plant

tissues, food and the work environment. In the USA, no DDE was detected in 3251 samples

obtained from 2001 to 2003 as a statistically selected, nationally representative sampling of

small drinking-water systems.

DDT is a persistent organochlorine pesticide that together with its metabolites can have a half

life in soil of up to 30 years. DDT was found in soil and sediment samples from all regions of

the globe, and residues are widely distributed in all types of soil. For example

in 2003, soils from elementary school yards in cities/towns within the state of Texas, USA,

were reported to contain DDE at concentrations between 1 and 60 ng/

In most countries, exposure of the general population to DDT occurs mainly through the diet.

Blood DDT and DDE levels in the general population have dropped at least two to three

orders of magnitude over time in most parts of the world.

Evidence of carcinogenicity in humans

The key epidemiological studies concerning DDT can be categorized as studies of

occupational exposure in farmers and commercial applicators, and studies involving the

general population using questionnaire- or biological-based exposure assessments to DDT

Associations between cancer and exposure to DDT have been investigated in more than 100

cohort and case-control studies from diverse countries. Nested and population based case-

control studies in China (which has a high incidence of liver cancer by worldwide

comparison) reported strong, dose-related associations between liver cancer and blood DDT

level after adjustment for potential confounders. No excess risk of liver cancer was reported

in a historical cohort study of men who sprayed DDT during a malaria control campaign in

Italy.

In studies on non-Hodgkin lymphoma, positive associations were reported in several cohort

and case-control studies in North America and Europe, while other studies found no



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association. Thus the large Agricultural Health Study of pesticide applicators in the USA

observed significant upward trends in risk of non-Hodgkin lymphoma in relation to several

indicators of DDT use while controlling for other suspected risk factors. However, a

retrospective cohort mortality study of applicators involved in an antimalarial campaign in

Sardinia, Italy, with almost exclusive use of DDT, did not identify any association between

DDT exposure and lymphoma. In the general population, evidence from case–control studies

based on self-reported or expert assessments from questionnaire was inconsistent, with no

association in several large studies and positive associations in some smaller studies.

Evidence was also inconsistent in studies using measurements in biological specimens as

biomarkers of exposure to DDT.

Six studies have assessed the association between DDT or DDE measurements in blood

samples and cancer of the testis of which two studies provide the strongest evidence. Positive

non-significant associations were found in two small case–control small studies using post-

diagnostic blood samples, while no association was detected in a large population-based

case–control study using post-diagnostic blood samples.

Increased risk of breast cancer in the wider community which may be associated with DDT

has been extensively researched. Although more than 40 studies conducted since 1993 were

reported, no clear association was found between breast cancer and DDT or DDE measured

in samples of blood or adipose taken in adulthood; however, the possible importance of early-

life exposure to DDT remains unresolved.

Evidence of carcinogenicity in animals

Numerous studies in mice, rats, and hamsters (mainly involving oral administration) provided

sufficient evidence in animals for the carcinogenicity of DDT and its metabolites DDE and 1-

chloro-4-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene (DDD). In mice, 12 studies gave

positive results, some for multiple tumour sites, with DDT consistently increasing the

incidence of benign and malignant liver tumours. Lymphoma incidence was also increased in

three studies. In rats, DDT increased the incidence of benign and malignant liver tumours in

four studies. In hamsters, DDT significantly increased the incidence of adrenal cortex

adenoma in two studies. In rodents, the metabolites DDE and DDD induced liver tumours in

two studies each.

IARC evaluation

DDT is probably carcinogenic to humans (Group 2A)

Studies on non-Hodgkin lymphoma and cancers of the liver and testis provided limited

evidence in humans for the carcinogenicity of DDT.

Broad perspectives

Exposure. In common with all pesticides for which adequate data are available, highest

human exposure to DDT involves those involved in its manufacture and application.

Normally, the only other consideration for pesticide exposure involves the general

community, with data involving high income countries for the most part. Uniquely amongst

pesticides, for DDT literally millions of people have been highly exposed this pesticide by

comparison with the community exposure in high income countries . This particular scenario

involves countries where, for decades, DDT was used to control and then eliminate malaria.



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In the general community, exposure to DDT as indicated by blood levels is decreasing, and

such exposure primarily occurs through diet. Levels of DDT in soil, where it is recognized as

a pollutant warranting remediation where practicable, are falling in high income countries.

Carcinogenicity. In relation to carcinogenicity, more extensive studies have been undertaken

in relation to DDT than for any other pesticide. The evidence positive evidence concerns

particular tumour types; there is no evidence that DDT may increase the incidence of all

tumour types. As already noted, clearest evidence for the carcinogenicity of DDT comes from

studies involving occupational exposure. The evidence that DDT is carcinogenic to humans is

strong, but not definitive.

With reference to non-occupational studies, concerning liver cancer, studies in China involve

a background of high liver cancer variously caused by aflatoxins (the products of a particular

mould) and hepatitis B virus. Extrapolation of these results to Australia and other high

income countries in relation to circumstances of DDT exposure, is difficult.

Clearest evidence in relation to non-Hodgkin lymphoma involved occupational exposure.

Studies involving community-based exposure were not conclusive. The strongest evidence of

association between blood levels of DDT and testicular cancer, while involving community-

based exposure, do not implicate any particular source of DDT. These findings are

complicated because unlike all tumour types mentioned thus far in this report, no chemicals

are recognized as proven to cause testicular cancer in humans.

Community exposure to DDT, as indicated by blood levels, is not associated with increased

risk of breast cancer.


Exposure DDT is detectable in soil as a result of previous usage. However in documenting

exposure to DDT, the IARC Monograph makes no reference to studies of human exposure to

DDT ( as indicated by blood levels, etc) attributable to historic usage of the insecticide; that

is, exposure as a result of living on sites or in a geographical area where DDT was used at

some past time for agricultural purposes or for malaria control. Given IARC policy to

document modes of relevant exposure as recorded in the medico-scientific literature, the clear

inference of this lack of reference to studies germane to this enquiry is that no such studies

are available. Consistent with that understanding, an independent search of the literature did

not indicate any such studies.

Carcinogenicity. In relation to the specific malignancies making up the Bellarine Peninsula

cancer cluster, cancer of the liver and non-Hodgkin lymphoma warrant consideration in

relation to possible exposure to DDT. The available data, however, provide no direct

evidence of DDT exposure consequent upon soil contamination as increasing risk of either of

these two malignancies in an Australian context.

Reporting of DDT in soil samples from schools in USA was not associated with speculation

concerning a consequential risk of cancer.

The possibility that environmental exposure to DDT (as indicated by blood levels) may be

associated with increased risk of breast cancer has been extensively researched, and



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consequentially excluded. There is no body of evidence that DDT exposure in any context is

associated with increased risk of multiple myeloma, brain cancers and leukaemia.

Organochlorine pesticides generally

Exposure

Consistent with discussion of exposure to dieldrin and DDT specifically, highest exposure to

organochlorine pesticides generally involves occupational exposure in the context of

manufacture and application of these compounds. Occupational exposure to organochlorine

pesticides generally is not detailed here. Rather the discussion is restricted to studies

implicating exposure as a consequence of organochlorine pesticides in soil.

Most studies assessing levels of organochlorine pesticides in soil or water as a consequence

of these compounds being used agriculturally in USA and Western Europe focus on

particular agents rather than total organochlorine pesticide levels. These studies do not

involve particular geographic locations associated with high usage, but concern

determinations that are applicable to agricultural land generally. Relevant findings from this

category of study have been included in the sections on dieldrin and DDT.

There are, however, some studies concerning soil contamination by organochlorine pesticides

which focus on single geographical locations. Specification of such sites in North American,

Western Europe or Australia is almost unknown. Rather, the studies in question concern sites

in Africa or Asia as typified by three studies involving China and India [5-7] where extreme

circumstances have prevailed in relation to over use or improper use of organochlorines.


There is no IARC Monograph evaluation of organochlorine pesticides generally, as distinct

from evaluations of some, but by no means all, individual such pesticides as exemplified by

Dieldrin and DDT (which have been identified in the present investigation), as well as

chlordane, hexachlorobenzene and lindane (which have not).

Virtually all studies of cancer risk which specify ‘organochlorines’ or ‘organochlorine

pesticides’ in the title involve the specific identification in serum, for example, of multiple

particular organochlorine compounds such as DDT or dieldrin. Such data for each of these

particular compounds are addressed in the two relevant IARC Monographs, where the

findings in relation to the particular pesticides are given due weight in the respective IARC

evaluations. Accordingly, such studies are not taken into account again here.

The one context in which carcinogenic risk is addressed in relation to organochlorine

compounds generally involves breast cancer. In the 1990s and earlier, the hypothesis that

endocrine-disrupting compounds, a chemical category recognized to include organochlorine

compounds, may cause breast cancer was prevalent. Thus Obrams et al [8] advanced this

hypothesis in a specific context

This paper discusses breast cancer patterns in Hawaii in the context of documented

episodes of exposure to two endocrine-disrupting chemicals, chlordane/heptachlor



14

and 1,2-dibromo-3-chloropropane (DBCP), at levels that sometimes exceeded federal

standards by several orders of magnitude.

Subsequent to such assessments, ‘Organochlorines and breast cancer risk’ was the subject of

a review by Calle et al in 2002 [9] with the byline

This column is provided to help practitioners discuss potential environmental and

workplace carcinogens, offering reassurance when patients’ fears are unfounded and

focusing legitimate concern when they are warranted.

The abstract to the review states that ‘organochlorine exposure is not believed to be causally

related to breast cancer’ in the following context

Although use of many organochlorine compounds has been banned in the United

States since the 1970s, some organochlorine compounds have accumulated and

persisted within the environment. As a result, measurable amounts can still be found

in human tissue. Because some organochlorine compounds act as estrogen agonists or

antagonists within in vitro and experimental animal systems, a possible association of

breast cancer risk with organochlorine exposure has been hypothesized and

investigated. Although a few studies support this hypothesis, the vast majority of

epidemiological studies do not. While some of these compounds may have other

adverse environmental or health effects, organochlorine exposure is not believed to be

causally related to breast cancer. Women concerned about possible organochlorine

exposure can be reassured that available evidence does not suggest an association

between these chemicals and breast cancer.


Addressing organochlorine pesticides generally in relation to testing for carcinogenicity in

experimental animals brings to mind the prospect of tumour induction following treatment of

animals with two, three or more such pesticides, each in a much lower dose than the

maximum which could be administered alone.

In practice, such testing in animals of multiple agents in combination and with tumour

induction as the endpoint is almost never undertaken. Specifically, no such combination

studies with different organochlorine pesticides are known. In practice, such experiments are

inordinately difficult to undertake, and extremely difficult to interpret.

IARC evaluation

There is no IARC Monograph evaluation of organochlorine pesticides as a class of

compounds.

Broad perspectives

The relevance of localised environmental contamination by organochlorine pesticides in

Africa and Asia to circumstances in Australia and other high income countries is difficult to

assess.



15

By comparison with the large number of publications addressing particular organochlorine

pesticides, consideration of studies titled in relation to organochlorine pesticides generally

provides no new insight. Almost invariably, studies apparently involving organochlorines

generally in point of fact concern the impact of multiple single organochlorines rather than

any cumulative effect of this category of pesticides. These observations apply to data

concerning exposure and data concerning carcinogenicity.


In respect of studies addressing carcinogenic risk, almost without exception relevant studies

involve specific compounds, as exemplified by dieldrin and DDT. The few studies predicated

on presumed or demonstrated exposure to organochlorine pesticides generally are challenging

in respect of how such exposure was quantified.

Accordingly, enquiry predicated on ‘organochlorine pesticides generally’ does not contribute

any new insight immediately relevant to the present enquiry.

Malathion

The following is based on the IARC evaluation of malathion published in 2017 [10]

Malathion is a non-systemic broad-spectrum organophosphate insecticide, which was first

commercialized in the 1950s, and continues to be produced and used in substantial volumes

in many countries. It is used for the control of insect pests of crops, pastures, and rangeland,

in residential areas, for control of ectoparasites on animals, and in pest-eradication

programmes.

Exposure

The IARC Monograph records that malathion is applied to control a large variety of insect

pests, including ants, aphids, caterpillars, flies, fruit flies, grasshoppers, hornets, moths,

mites, mosquitoes, scorpions, spiders, wasps, and weevils, as well as ectoparasites of cattle,

horses, swine, poultry and pets (including fleas on dogs and cats). Additionally, malathion is

used to treat head and body lice on humans. The ‘Production and Use’ section of the

Monograph notes that Malathion is used for mosquito abatement in public-health

programmes in industrialized and less industrialized countries.

Occupational exposure to malathion has been measured in farm and greenhouse workers and

in pest- and vector-control workers. Dermal contact has been found to be the most important

route of occupational exposure.

The general population can be exposed to malathion from residues on food, from living near

areas where malathion is sprayed, or through personal use of products containing malathion.

Measured concentrations of malathion in environmental media are generally very low and

malathion is not persistent, since it degrades relatively quickly



16


Several studies provided useful information; in particular, one cohort study, the US

Agricultural Health Study (AHS) based on pesticide applicators, covers 11 malignancy types

in adults and childhood cancer. There are two case–control studies nested in occupational

cohorts.. Four independent case–control studies, three of them in adults (in the midwest USA,

Canada, and Sweden) and one in children (Costa Rica) have also estimated the association

between exposure to malathion and haematological malignancies. Three additional case–

control studies explored other cancer sites: prostate (Canada), soft-tissue sarcomas (Canada),

colorectum (USA) and glioma (USA).

Case-control analyses of occupational exposures reported positive associations with non-

Hodgkin lymphoma in the USA, Canada, and Sweden, although no increased risk of non-

Hodgkin lymphoma was observed in the large AHS cohort. Occupational use was associated

with an increased risk of prostate cancer in a Canadian case-control study and in the AHS,

which reported a significant trend for aggressive cancers after adjustment for other pesticides.

No positive association was observed for other cancer sites studied: soft tissue sarcoma,

glioma, colorectum, melanoma, bladder, or kidney, but only one study was available for each

site.

No studies involving risk to the general community, for example, on the basis of blood levels

of malathion, were available.


Two feeding studies in mice were reviewed. In the first, malathion increased the incidence of

hepatocellular adenoma in male mice with no significant increase in tumours in female mice.

In the second, a significant increase in hepatocellular adenoma (malignant liver cancer), and

of hepatocellular adenoma or carcinoma (combined) in males occurred. There was no

significant increase in hepatocellular carcinoma considered alone in any of the treated groups

Four feeding studies on malathion in male and female rats were reviewed. In the first and

second studies, no treatment-related tumours were reported in males or females. In the other

two studies, malathion increased thyroid carcinoma in males, and increased hepatocellular

adenoma or carcinoma (combined) in females. Subcutaneous injection of malathion caused

mammary gland adenocarcinoma in female rats.

IARC evaluation

Malathion is probably carcinogenic to humans (Group 2A).

There is limited evidence in humans for the carcinogenicity of malathion. Positive associ-

ations have been observed with non-Hodgkin lymphoma and cancer of the prostate

Broad perspectives

Exposure By comparison with information available for dieldrin and for DDT concerning

environmental contamination and consequent human exposure, scant evidence is available

concerning malathion. Malathion degrades rapidly and does not persist in soil or water.



17

Carcinogenicity. Findings concerning occupational exposure to malathion and two types of

malignancy – non-Hodgkin lymphoma and prostate cancer – have been implicated. The

absence of data concerning non-occupational exposure to malathion and these two types of

cancer, and the fact that malathion is not environmentally persistent, taken together provide a

poor basis for speculation about any carcinogenic risk malathion presents to the general

community

Specification about exposure situations in which increased risk of prostate cancer might be

attributable to malathion is complicated by the fact that no recognized chemical carcinogen

has been proven to cause prostate cancer.


Exposure. Consideration of exposure and carcinogenicity of malathion in relation to the

Bellarine Peninsula cancer cluster is dominated by the qualification that this chemical (and

others like it) may have been used rather than them being known to have been used.

There appears to be no direct evidence, or reasonable inference, that residents of the Bellarine

Peninsula have been exposed to malathion to a greater extent than has the Australian

community as a whole, or those parts of the Australian community where mosquito

eradication has been focused.

Carcinogenicity. There is scant, if any, direct evidence of increased risk of non-Hodgkin

lymphoma as a result of community exposure to malathion. A basis upon which such a

suggestion may be made is not immediately evident. Concerning other tumour types of

special interest in relation to the Bellarine Peninsula cluster, no plausible relationship to

malathion is evident.

Chemicals possibly used for mosquito spraying

A focus on chemicals possibly used for mosquito spraying on the Bellarine Peninsula appears

to be a secondary matter in relation to the initial reporting of this cluster. I have been unable

to locate any scientific assessment prompting attention being given to mosquito control in the

present context, and therefore the following is based on literature search and current

knowledge of any carcinogenic risk attributed to relevant pesticides.

Agents of interest in the context of their possible use for mosquito control on the Bellarine

Peninsula are specified as

Temephos, malathion, fenthion, synthetic pyrethrums, and organophosphorus

pesticides generally.

The carcinogenicity of malathion is subject of an IARC Monograph and, accordingly, this

pesticide has been addressed. For the remaining chemicals and classes of chemicals, available

information concerning carcinogenicity is addressed in the sections below.



18

General perspective

Spraying of pesticides to control mosquitos has never been recognized as a matter presenting

a carcinogenic risk to humans. There is no literature base to be assessed in the current

context. A study on ‘Exposure to Mosquito Coil Smoke May be a Risk Factor for Lung

Cancer in Taiwan’ was the study recovered upon literature search and is only available in

Chinese. It is not relevant. Otherwise, in the course of literature search, the most precisely

identified publication was ‘Mosquito vectors and the spread of cancer: an overlooked

connection?’ [11] which addresses the possibility that mosquitos may play a role in cancer

etiology in some parts of the world. Again, not relevant.

Exposure

No peer-reviewed studies were identified which address mosquito control in the Bellarine

Peninsula region. In Australia generally, mosquito control is undertaken to reduce the spread

of certain infectious diseases. No attempt has been made, given an extremely limited

timeframe, to address occupational exposure to relevant pesticides in the context of mosquito

control in Australia. Residential or environmental exposure as a consequence of mosquito

spraying in Australia does not appear to be a health consideration in the overall context of the

safe use of pesticides generally.

There is not sufficient information available for separate consideration of exposure, and

specifically non-occupational exposure, to each of the pesticides or classes of pesticides of

interest. Thus, concerning exposure to pyrethrums, the only study located involved pyrethrum

and related residues in water and sediment from a lake in Ghana; information that could have

no direct relevance to the present enquiry. Ghana is a country with endemic malaria and

subject to mosquito control which is remote from any situation in Victoria.


Temephos and fenthion. No information on human studies of the carcinogenicity of these

two pesticides was located.

Synthetic pyrethrums. Search against synthetic pyrethrums and cancer yielded no peer

reviewed publications addressing carcinogenicity.

Organophosphate pesticides generally

Studies referring to ‘organophosphate pesticides’ invariably include, or are restricted to

findings specific for individual organophosphates, rather than primarily involving data for

organophosphates generally. Even so, only a small number of studies are available. None of

the studies reported below makes specific reference to use of these agents to control

mosquitos.

Data from three population-based case control studies conducted in four US states was

pooled to evaluate the relationship between the use of organophosphate pesticides and non-

Hodgkin lymphoma among white male farmers [12]. Likely causality was not established and

the strongest associations concerned use of diazinon specifically



19

Personal use of specific organophosphate pesticides and cancer incidence were evaluated

among female spouses of pesticide applicators in the prospective Agricultural Health Study

cohort [13]. Use of any organophosphate pesticide was associated with an elevated risk of

breast cancer (relative risk 1.2). Malathion, the organophosphate pesticide most commonly

reported in the study, was associated with increased risk of thyroid cancer (relative risk 2.4)

and, counterintuitively, decreased risk of non-Hodgkin lymphoma (relative risk 0.64).

Studies on particular organophosphate pesticides including fonophos [14] and phorate [15]

are available, but these are not established as likely to cause any particular cancer and the

agents are not specified as relevant to the present enquiry.

IARC evaluation

There are no IARC evaluations for any of the insecticides specified in this section. There are

no IARC evaluations for organophosphate pesticides generally or for mosquito control agents

or any similar terminology

Broad perspectives

By comparison with data available for the carcinogenicity of dieldrin and DDT, information

regarding carcinogenicity of agents discussed in this section does not provide a basis for

discussion regarding matters such as risk of cancer consequent upon non-occupational

exposure.


On the basis of information available concerning the possible carcinogenicity of temephos,

malathion, fenthion, synthetic pyrethrums, and organophosphorus pesticides generally, no

basis exists for speculating that these agents have a causal role in the Bellarine Peninsula

cancer cluster.

Inferences from cancer attributable to point source pollution.

The medico-scientific literature contains no account of a burden of multiple types of

malignancy being attributable to, either in whole or in part, exposure to chemicals, and

specifically pesticides, used in a relevant location at some past time. This situation might be

expected because no single carcinogen, or group of chemically-related carcinogens, is known

to cause cancer in general, or a group of cancers as diverse as breast, brain, and liver cancers

together with lymphoma and leukaemia.

The number of individual cancer clusters described in the literature is small compared to the

number known to have been reported to health authorities (see Appendix 2). Even with this

limitation, every cancer cluster described in the medico-scientific literature involves a single

tumour type or a small number of closely-related types of malignancy.

For these reasons, consideration of how information in the peer-reviewed medico-scientific

literature might provide insight in the present context necessitates a broad approach.



20

Point source of occupational carcinogens causing cancer

Point sources of carcinogen exposure can cause cancer in surrounding communities, as

evidenced by epidemiological studies initiated without reference to cancer clusters being

reported. Typically, the situation comes about when carcinogens affecting relevant

workforces, also affect the surrounding community, albeit with a much lesser impact. Classic

examples include lung cancer and mesothelioma caused by asbestos [16] and lung cancer

attributable to emissions from iron founding and steel production [17]. Such cases

acknowledged, extrapolation from instances of occupational cancer must be undertaken with

care. Increased cancer in the community may not be detectable. No increased angiosarcoma

of the liver (an extremely rare cancer, resulting in the carcinogenicity of vinyl chloride being

discovered) was evident in residents living close to vinyl chloride production facilities [18].

NSW cancer registry data recorded from 1972 have not revealed increased incidence of lung

cancer in Wollongong or Newcastle.

Cancer from industrial contamination and localized pollution

As a general principle of public health, environmental pollution is unacceptable and, in

relation to any localized impact, remediation of contaminated sites is implicitly required.

Remediation may be an imperative because of odour or when any adverse health outcome,

particularly respiratory disease, is evident. Those principles are not compromised or qualified

by any of the following discussion about cancer.

Some evidence of increased respiratory disease, birth defects and various tumour types,

among other adverse effects, has been recorded in studies of particular contaminated sites

[19;19]. With reference to cancer however, there is no consistent body of evidence

concerning contaminated sites affecting the wider community by comparison with the body

of evidence about the local residential impact of occupational carcinogens. Moreover,

negative results have been documented

In US, the Superfund Research Program (SRP) is an multidisciplinary, translational research

program that for 25 years has sought scientific solutions to health and environmental

problems associated with hazardous waste sites. In the most recent assessment [20], SRP

refers to the potential for carcinogen exposure from contaminated sites, although there is no

reference to a contaminated site being recognized in the context of standard-practice use of

pesticides in agriculture. No instances of increased cancer incidence attributable to

contaminated sites are recorded in the SRP overview.

Love Canal in northwestern New York state was one of the most seriously contaminated

hazardous waste sites (and one of the most investigated) in the United States. The site

contained approximately 21,800 tons of at least 200 different chemicals. Some reproductive

toxicity could be identified [21]. However, no increased incidence of cancer was initially

evident [22]. Almost 20 years on, some increase in bladder and kidney cancer was evident in

the relevant community, but a direct connection with the contamination was not recognized

[23]

Soil contamination is monitored in Europe [24]. The identified contaminated sites number

around 342 thousand. Municipal and industrial wastes contribute most to soil contamination

(38%), ahead of industrial/commercial sector (34%). Mineral oil and heavy metals are the



21

main contaminants. Pesticide contamination has not been specifically described in this

context.

Community breast cancer attributable to pesticides

As distinct from situations in which specific point sources of carcinogenic or toxic material

are evident, some analogy may be drawn between the Bellarine Peninsula cluster and the

investigation of pesticides as a cause of breast cancer in the general community. A basis

exists for supposing that certain categories of pollutants, including some pesticides, may

cause breast cancer [25]. In respect of pesticides, the most comprehensive such investigation

involved Long Island, New York, USA.

The study of breast cancer on Long Island was probably the most comprehensive of its type

that has been undertaken. One aspect included measure organochlorine pesticide blood levels

in the relevant community [26]. Pesticides were not identified as the cause of increased breast

cancer. The outcome of the investigation undertaken [27] was specified as follows:

In the early 1990s, breast cancer advocates petitioned the United States Congress to

investigate the high rates of breast cancer on Long Island in the state of New York.

The resulting law led to the Long Island Breast Cancer Study Project — more than ten

research projects designed to study the possible causes of this increased incidence of

cancer. This project reported that there was no evidence that environmental exposures

were responsible.

In an unrelated population-based case–control study of women residing in Cape Cod,

Massachusetts diagnosed with breast cancer in 1988–1995, pesticide exposures were assessed

dating back to 1948 when DDT was first used there [28]. No overall pattern of association

between pesticide use and breast cancer was found. There were modest increases in risk

associated with aerial application of persistent pesticides but confidence intervals did not

exclude the null.

By comparison with the two studies described above, studies involving pesticide exposure

and multiple types of malignancy as have been implicated in the Bellarine Peninsula cancer

cluster have not been reported.

Geneeral remarks

Extreme point source pollution, up to and including thermonuclear warfare, has been

associated with cancer causation in the general community. Corresponding studies of cancer

possibly attributable to less severe, but clearly evident pollution, exemplified by industrial

waste and contaminated sites, have been undertaken. Diverse results, including no association

in some instances, have been reported. Finally, studies involving the carcinogenic impact of

pesticides on incidence of breast cancer in particular communities have been undertaken, but

there is no body of evidence to suggest a pattern of increased cancer in the manner inferred

for the Bellarine Peninsula cancer cluster.

While certain of the research described in this section generated community concern and

advocacy, none of these investigations were prompted by a cancer cluster report. Advocacy

and community involvement came later in some cases. However the key initial studies were



22

population-based epidemiological surveys, and not health authorities being alerted to 10-15

individual cases as typifies most cancer cluster reports.

Conclusion

Examination has been made of current knowledge concerning circumstances of exposure and

the related evidence for carcinogenicity in respect of the various specific pesticides and

categories of pesticides implicated in the Bellarine Peninsula cancer cluster. Insight has also

been sought by reference to medico-scientific publications concerning localized cancer

prevalence attributed to point sources of pollution and to non-occupational exposure to

pesticides.

In light of this evidence, causation of multiple tumour types specified in relation to the

Bellarine Peninsula cancer cluster by non-occupational exposure to pesticides specifically as

present in soil as a result of earlier usage, is not plausible. The pesticides DDT and dieldrin

are the chemicals for which most relevant information is available, but neither of these can be

specified as a plausible cause of this cancer cluster. The possibility that cancer causation by

pesticide exposure has occurred cannot be excluded with absolute certainty: a scenario which

applies to all investigations of this type.

As indicated throughout this report, information concerning risk of cancer following

particular levels of exposure to relevant pesticides is crude in many instances. The matter of

level of exposure is essentially restricted to distinction between occupational and non-

occupation exposure, with the former involving the higher level of exposure and the greater

risk of cancer where cancer is evident at all.

Beyond this distinction between occupational and non-occupational or environmental

exposure, information on what level of exposure to a particular chemical might cause cancer

cannot be specified in analytical terms both in respect of the present matter and generally.

Inferences about level of exposure may be attempted in relation to agents of proven

carcinogenicity such as tobacco smoke, asbestos or x-irradiation. Such inferences are

markedly more uncertain in respect of agents strongly implicated, but not proven to cause

human cancer.

No circumstance of exposure to any carcinogen is identified in the medic-scientific literature

in terms of the level that might cause cancer in humans. To do so would implicitly identify a

threshold: a matter which remains contentious, particularly in relation to its public health

implications.

No carcinogen, or category of agents such as chemically-similar pesticides, is recognized as

causing increases in incidence of cancer at all anatomical sites or cancer of all types. No

carcinogen is recognized as increasing incidence of non-Hodgkin lymphoma, multiple

myeloma, brain tumours, breast cancer and leukaemia: the malignancies identified in the

Bellarine Peninsula cancer cluster. Generally speaking, scientific investigation of cancer

clusters is not undertaken unless the cluster involves a single cancer type (breast cancer,

leukaemia, etc.) or an extremely low number of biologically-related tumour types.



23

In the investigation of cancer clusters, determination of whether cancer cases in the

community under scrutiny may plausibly be attributed to particular carcinogen(s) is

independent from, and not ultimately subject to the matter of whether a greater-than-expected

number of cancer cases has occurred. This report does not address whether a greater-than-

expected cancer incidence in the Bellarine Peninsula has occurred, and makes no comment on

that matter.



24

Appendix 1. Investigations of highly publicised cancer clusters The truth about cancer clusters (and why you’ll never hear it otherwise)

Cancer clusters are big news and no-one needs to be told what they are. Best known to

Australians are probably the ABC breast cancer cluster in Brisbane, as portrayed in two

episodes of Australian Story on ABC TV, and the impact of water contamination by

chromium-6 on the town of Hinkley, California as portrayed in the film ‘Erin Brockovich’.

Cancer clusters involve big money: the cost of relocat8ing ABC broadcasting in Brisbane and

several hundred million in damages recovered on behalf of the citizens of Hinkley thanks to

Erin.

Typically, in Australia, publicity about particular cancer clusters comes at one point, or is

most intense at one point: either when the cluster is initially reported or when the community

have rejected the state-based Health Department investigation which has failed to ‘confirm’

the cluster. In such circumstances, the affected community may seek parliamentary

intervention or a new initiative by the authority seen to have failed in the first instance.

After that, as the further investigation concludes, or even later down the track: nothing is

notified by way of media attention. There is no reporting of what might be termed the bottom

line’. Such information is provided here.

The ABC Breast Cancer Cluster

ABC staff in Brisbane rejected the finding by Queensland Health Department that no basis

existed to attribute a greater-than-expected number of breast cancer cases among ABC staff

working at Toowong to some specific cause. The staff prevailed on management to appoint

an ‘Expert Committee’ to investigate the cluster. The Committee’s initial report recognized

that the 11 cases of breast cancer among female staff of a particular age represented six times

the expected number. The Committee went on to specify that the likelihood of such a

scenario occurring due to chance was less than one in a million. ‘One in a million’ was the

title of a double episode of Australian Story about the cluster [29].

Subsequently, the Expert Committee revised the role of chance as accounting for the cluster

to 1 in 25. The ABC commissioned a formal epidemiological study of breast cancer amongst

all women employed by the ABC Australia wide. The study duly reported no evidence of

above expected level of breast cancer in all other centres, while confirming that in Brisbane

alone a greater-than-expected number of cases had occurred [30]. An accompanying editorial

noted that chance could now be seen as the most likely explanation for the cluster, but this

finding would never be widely communicated [31].

Two years later, a genomic analysis of the 11 breast cancer cases was published [32]. This

investigation found (a) no evidence of viral genomes in DNA from any of the tumours

analysed and (b) that each of these breast cancers was no more closely related to any of the

others in the cluster than to breast cancer genomes in Queensland as a whole. To my

knowledge, no other cancer cluster in the world has been subject to such a genomic analysis.

The authors concluded that chance was the most likely explanation for the cluster. No

publicity was accorded to this scientific publication.



25

Almost 15 years has passed since initial publicity was accorded to the ABC breast cancer

cluster. In that time, to my knowledge, no report of increased incidence of breast cancer

among broadcast workers worldwide has appeared in the peer-reviewed literature.

Taken together, the absence of any increased incidence of breast cancer among ABC

employees apart from those working in Brisbane, the results of the genomic analysis and the

absence of any related occurrence worldwide mean that confidence in concluding that the

cluster was due to chance now approaches scientific certainty.

Despite the failure to recognize any likely cause of the cluster at any point throughout the

investigation, closure of the ABC facility at Toowong and relocation of staff was fully

justified. Tragically, one women in nine is diagnosed with breast cancer in Australia, the

likelihood of that diagnosis increasing with age [33]. Inexorably, among the cohort of women

employed by the ABC in Brisbane, breast cancer will continue to be diagnosed. Had not the

staff been relocated, all such individual diagnoses would have been accompanied by the

headline ‘Yet another case of breast cancer in the ABC cluster’.

The anxiety felt by the women who were diagnosed, and their fellow ABC employees

justified a scientific investigation. However, as judged by reporting in the last five years, the

women who worked at Toowong have never been formally advised of the true situation: that

they have nothing to worry about. Apart from allowing reassurance to be provided, the

scientific investigation of the ABC breast cancer cluster has contributed nothing to current

understanding of the etiology of breast cancer.

The Port Kembla leukaemia cluster

Prompted by diagnosis of leukaemia in three young people living close to the Port Kembla

steelworks, and expanded to include all persons under the age of 50 living in that region and

diagnosed with leukaemia, this is the second most intensively investigated cancer cluster in

Australia. The leukaemia cases were attributed to benzene emissions from the steelworks. A

comprehensive NSW Health investigation undertaken. That investigation rejected the

‘benzene hypothesis’ and failed to reveal any likely cause of the cluster [34]. These findings

were rejected by the community who instituted an independent enquiry. That enquiry resulted

in a publication which included a fraudulent diagram purporting to demonstrate risk of the

leukaemia linearly, but inversely, related to distance of residence from the steelworks.

In the ensuring 20 years, no increased incidence of leukaemia in the Port Kembla region has

been evident from cancer registry data as reported annually. Investigation of this cluster

contributed nothing to current understanding of the etiology of leukaemia.

Cancer and chromium-6 in the film ‘Erin Brockovich’ The film portrays the role played by a paralegal officer, Erin Brockovich in achieving award

of massive damages against a corporation held accountable for pollution by hexavalent

chromium (commonly referred to as chromium-6) of water provided to the town of Hinkley

in southern California. Occurrence of the pollution is recorded by relevant authorities and is

not in question. However, although inhaled chromium-6 is proven to cause lung cancer in

smelter workers exposed to the metal by inhalation, ingested chromium-6 as a result of water

contamination has not been established to cause cancer of any type in humans. No increased



26

incidence of cancer in Hinkley is documented in the medico-scientific literature, nor is the

event mentioned in textbooks addressing cancer attributable to water contamination.

IARC evaluation of the carcinogenicity of chromium makes no mention of cancer attributable

to ingested chromium in southern California and does not record causation or likely causation

of human cancer from ingested chromium-6 [35]. Indeed, the only specific mention of

Hinkley and chromium-6 in the medico-scientific literature is a brief commentary in the pre-

eminent journal ‘Science’ [36]. The commentary was prompted by the resignation of three

members of the Board of the American Public Health Association. The Board members,

aware of the carcinogenicity of chromium-6 as summarised above, resigned following a

resolution of the Board to make an award to Erin Brockovich (the person, not the film) for

raising awareness of environmental carcinogenesis.

Arguably, the greatest scientific travesty evident in the film does not involve that

carcinogenicity of chromium-6. The greatest travesty is the understanding that cancer

attributable to a specific cause may be self-evident.

The PFAS-related cluster at Fiskville, Victoria The clearest indication of the dichotomy between the medico-scientific literature and media

speculation about cancer clusters involves the cancer cluster at a fire-training college at Fiskville

Victoria. As reported to health authorities, and subject to media attention, the community affected

attributed a perceived increase in cancer incidence to PFAS (per- and polyfluoroalkyl substances):

chemicals which were a principal ingredient in firefighting foam. Higher than average levels of PFAS

were detected in ground water near the college

Following an investigation by staff from Monash University, headlines read ‘Fiskville cluster

confiremed’ since higher than anticipated incidence of cancer in those associated with the college was

evident. This result, however, did not establish causation by PFAS.

The scientific paper concerning Fiskville [37] which prompted the headline quoted above does not

include the word ‘cluster’ at any point because ‘cluster’ has no scientific meaning in respect of cancer

(see Appendix 2). The purpose of the study as described in the publication is:

to investigate the cancer and mortality of groups likely to have had a high, medium

or low risk of chronic exposure to flammable chemicals, combustion products, foams

and recycled fire water

The result is summarized as

The high group had a statistically significantly increased overall cancer incidence

despite small numbers. We found significant increases in brain and nervous system,

melanoma and testicular cancer in the cohort.

However, though the ‘high group’ might be supposed to have reference to PFAS, in fact

The Country Fire Authority assigned firefighters into three groups: high (practical

areas for drills operators and paid Fiskville instructors), medium (volunteer and paid

regional staff instructors) or low (paid practical firefighting trainees)



27

Thus the high group might be supposed to have high exposure to flammable chemicals,

combustion products, foams and re-cycled water. In the whole of this publication, PFAS or

any chemical synonym for this term is not mentioned because no scientific basis exists to do

so. Far from being caricatured as confirming the cause of a cancer cluster, the Conclusion of

the study (quoted in full) was

Dealing with supplied records can be problematic but despite the small numbers, we

identified an increased risk of cancer for the high group. The mortality data suggested

that there was under-ascertainment for the medium and low groups which

underestimated risk and a possible reporting bias for brain cancer. Small cohorts can

still provide statistically significant findings when investigating locations for cancer

risk.

The possibility that contact with PFAS increased cancer incidence at Fiskville cannot be

excluded. Thus far, in common with the overwhelming majority of cancer clusters, there is no

direct evidence that it did. As occurred for the ABC breast cancer cluster, passage of time

will clarify the situation.

Concluding remarks

As explained further in Appendix 2, cancer clusters (meaning perceptions of increased cancer

cases reported to health authorities by those affected) warrant scientific investigation in order

to provide reassurance to relevant communities. For the relatively few examples of cancer

clusters which are subject to scientific investigation, unequivocal resolution of the matter

may only be possible after years or decades.

Scientific investigation may confirms that an increased incidence of cancer has indeed

occurred, but this is not always the case; for some clusters which are reported, no increased

incidence of cancer is evident. Regardless of the matter of increased cancer incidence,

scientific investigation almost invariably confirms that no recognized carcinogen(s) is

responsible. Such investigations may take one or two years. In subsequent years, there are

rarely any reported circumstances subject to scientific investigation which tend to confirm the

original concerns about cancer causation.

Media interest is focused on the initial expression of concern and/or rejection by the affected

communities of the assessment made by health authorities. There is never any media interest

in a definitive assessment which comes after years or decades. Almost invariably, on a

worldwide basis, that assessment provides that chance is the likely explanation.



28

Appendix 2. Cancer clusters as contributing to the discovery of carcinogens Cancer clusters have never revealed a new cause of cancer

The whole point of reporting a cancer cluster to health authorities is that a specific factor may

be shown to account for the perceived greater-than-expected number of cancer cases.

Identification and removal of the factor responsible for a cluster will presumably halt an

otherwise inexorable increasing number of cancer cases. More widely, controlling relevant

exposure will prevent such events occurring elsewhere.

Such goals are implicit in the reporting of a cancer cluster. They have never been realized

consequential to the reporting of a cancer cluster, though in theory, this could occur.

That reporting of a cancer cluster to health authorities has not resulted in cancer causation

being identified is counter intuitive, particularly since, for infectious disease, the

corresponding causative agent(s) is identified as a matter of standard practice [38]. A key

factor in the distinction being made is that infectious disease may be evident with 24 hours of

exposure, whereas cancer following point-source pollution, where such cancer does occur,

may take decades, with decades also separating the first and last cases.

Cancer clusters have never revealed a new cause of cancer

Cancer only occurs in a minority of people known to be exposed to a particular carcinogen.

The carcinogenic exposure may occur over several years or decades, and resultant cancers

may be diagnosed while exposure is ongoing or be diagnosed decades after exposure ceased..

Consequently, cancer causation by an otherwise unrecognised carcinogenic exposure is never

self-evident, but evident once certain findings have been analysed. The epidemiologist, (the

late) Sir Richard Doll, who was among the first to prove that smoking causes lung cancer was

a smoker as he oversaw initial results of an ongoing survey of British doctors regarding lung

cancer development [39]. Doll is on record as saying that smoking was not his prediction as

the causative agent; he ceased smoking immediately the numbers were crunched.

Some epidemiological studies which have resulted in carcinogens being identified have been

prompted by an astute physician reporting more of a particular tumour type than would be

expected [40]. A gynaecologist in USA reported on eight adolescent girls with vaginal cancer

(a malignancy which is extremely rare in this age), noting that theit mothers had all been

treated with diethylstilbestrol during pregnancy [41].

Hence the only known human transplacental carcinogen was discovered. Later studies proved

that approximately one woman in a hundred treated with diethylstilbestrol had a daughter

who developed vaginal cancer. Was the carcinogenicity of diethylstilbestrol discovered

because two (or more) mothers with afflicted daughters met and had concerns? The odds

against such a meeting would be thousands to one against, even presuming all such tumours

developed within months rather than years of one another [42].

Chance did play a role in this piece of carcinogen history. Doll [42]records that the

carcinogenicity of diethylstilbestrol owes its discovery to a power failure at the

Massachusetts General Hospital which trapped a gynaecologist and a pathologist in an

elevator for 3 hours and they had no option but to talk.



29

Scenarios involving astute physicians triggering epidemiological studies involve multiple

carcinogen discoveries including asbestos and vinyl chloride. None of the corresponding

publications refer to ‘clusters’, but decades late, some would.

Recognition of ‘true’ cancer clusters

Review of the outcome of cancer cluster investigations in USA [43] involved 428

investigations evaluating 567 cancer organ sites of concern from among the thousands of

clusters reported to 50 state authorities over the period 1990=2010. Of the 567 cancer sites or

categories investigated, a perceived increased incidence was confirmed for 72 (13%). Of

these, three (3) reports (0.5% of the original 567) indicated at least some evidence of an

association between disease and hypothesised causal exposures.

In short, a perception of increased cancer incidence may be confirmed in a cancer cluster

investigation. However demonstrating a credible cause is almost unknown. Commentaries on

cancer cluster investigations refer to the obligation of health authorities to investigate such

reports as the basis for providing reassurance. However there is complete agreement that

cluster investigations do not provide insight regarding cancer causation [44-47].

Cancer cluster investigations can result in epidemiological studies which stand alone [30;37]

rather than being presented in the context of a cluster investigation. The last cancer cluster

investigation conducted in Australia and described in the peer-reviewed literature occurred in

1999[34] prompting an editorial entitled ‘Cluster investigations: are they worth it?’[48] with

the by-line ‘The odds are against finding a cause, but we must address community concerns’.

No report or commentary about cancer cluster investigation(s) in the peer-reviewed literature

has ever specified ‘This is a confirmed/true cancer cluster’ or words to that effect with the

exception of a single scenario. In a discussion of cancer clusters for practitioners, Thun and

Sinks [49] suggest one context in which a true cancer cluster may be recognized. They note

that initial case reports that ultimately resulted in carcinogen discovery often involved a local

community. The cases of vaginal cancer mention earlier were treated at Massachusetts

General Hospital; the patients were residents of Boston. To that extent, a true cluster based on

diethylstilbestrol-induced vaginal cancer might be said to have existed in Boston during the

1960s. This notion has not been endorsed by others. However, in the initial reports

concerning diethylstilbestrol, asbestos or vinyl chloride, the word ‘cluster’ was never used.

Cancer clusters have no place in cancer epidemiology or cancer science

Cancer clusters represent a focus for community concern and health authorities must respond

[44-47]. This need to provide assurance is exercised despite such authorities being aware that

cancer clusters – that is perceived increased cancer incidence prompting community members

to notify authorities – have no place in the discovery of new carcinogens. If formal testimony

were needed to establish what is common knowledge to relevant professionals, IARC

Monographs could be cited in the following context.

In excess of a thousand agents and circumstances (such as work as a painter) have been

subject to Monograph evaluation as published in over one hundred and twenty volumes. All

monographs, possible excluding some of those which are re-evaluations, outline accrual of

initial findings that prompted extensive epidemiological and/or comprehensive animal

bioassays. In the whole of those one hundred and twenty volumes, there has never been a



30

single instance of a cancer cluster being cited as contributing to, let alone establishing,

carcinogenicity of the matter under evaluation.

There is no chapter on ‘Clusters’ in any textbook on cancer epidemiology. In such texts as are

immediately available to me [50-52] the word ‘cluster’ does not appear in the index of any

(except for one reference to genes predisposing to leukaemia being clustered on a particular

chromosome).

The word ‘cluster’ does not appear in the Preamble to IARC Monographs which outlines

which relevant research publications are taken into account. The same may be said of other

authoritative assessments of carcinogenicity exemplified by World Cancer Research Fund

[53] or the US Report on Carcinogens [54].

Again, it must be emphasised that the absolute statements above concern cancer clusters; they

do not necessarily apply to clusters involving other diseases, and the exact opposite is true for

infectious disease clusters.

Concluding remarks

The fundamentals covered in this appendix will never be widely communicated. Cancer

clusters are a major focus for media and the legal profession. Cancer is overwhelmingly the

disease feared most by Australians [55] and media reports about insidious cancer causation

are winners. For the legal profession, the benefit from cancer clusters is equally clear.

In identifying the media and the legal profession as making adverse effects from cancer

clusters widely recognized, there is no suggestion made here of conspiracy and no suggestion

of any intent to mislead or defraud. There is also no imputation of improper conduct or lack

of professionalism by any category of persons, and certainly not in respect of any particular

person(s). Rather, the situation described is the outcome of how our community functions.

Communication is fundamental to the perception of cancer clusters and the related failure to

understand what (apart from smoking and asbestos) causes cancer [56].

Health authorities can declare what is proven to cause cancer but can’t list what is proven not

to. Whether it be in relation to media enquiry, or in the course of giving sworn evidence,

when faced with

Can you assert that it is impossible for the exposure in question to have resulted in, or

contributed to cancer causation?

Are you able to inform us that this product is absolutely safe?

the response ‘No, but it is extremely unlikely that…’ simply don’t deliver.



31

Appendix 3. WHO carcinogen evaluation procedures IARC Monographs on Evaluation of Carcinogenic Risks to Humans

Medico-scientific findings about the carcinogenicity (ability to cause cancer) of specific

agents, or of particular circumstances of exposure to multiple agents, are evaluated by

International Agency for Research on Cancer (IARC), an arm of the World Health

Organization (WHO). These evaluations, published in the context of a multi-volume series

called IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, are the most

authoritative available worldwide. In relation to such evaluations involving circumstances of

exposure, the most common situations addressed in this context involve particular

employment categories (for example, work as a painter or as a hairdresser).

This appendix is an ad hoc summation of IARC Monograph procedures, and as such is not

definitive in every aspect. The definitive statement on procedure is the Preamble to the

Monographs. The Preamble, and indeed all the IARC Monograph evaluations are available on

the corresponding website http://monographs.iarc.fr

If it is determined that the agent or circumstance of exposure definitely causes cancer in

humans, the agent or circumstance of exposure is listed as carcinogenic to humans (Group 1).

Group 1 currently includes tobacco smoke, asbestos and work as a painter. If the data

available are evaluated as being less than definitive but nonetheless compelling, the agent or

circumstance of exposure may be evaluated as probably carcinogenic to humans (Group 2A.)

Group 2A evaluations currently include work as a hairdresser involving exposure to hair dyes

and some specific pesticides including dieldrin and DDT. If the evidence is less clear still,

Group 2B involves agents and exposures deemed possibly carcinogenic to humans (Group

2B). Group 2B currently includes work as a dry cleaner and the herbicide 2,4-D. If all the

available data are not adequate to indicate that the agent or circumstance of exposure is

possibly carcinogenic to humans, an evaluation of not classifiable as to its carcinogenicity to

humans (Group 3) is made. Group 3 currently includes drinking coffee. (Italics in this

paragraph are as used in the original IARC evaluations to indicate terms are defined within

the Monograph procedure).

Allocation of agents to particular Groups is predicated on consideration of the relevant

epidemiological (cancer in humans) and experimental (cancer in animals) data, such evidence

both humans and animals being separately evaluate as sufficient, limited or inadequate

(italics used in the original). Overall evaluation (allocation to Group 1, 2A, 2B or 3 as

described earlier) takes account of the epidemiological and experimental data, together with

mechanistic (that is evidence from laboratory studies) and any other relevant information that

is available.

Cancer epidemiological investigations are of two types: case-control studies and prospective

or cohort studies.

Case-control studies are based on identifying individuals diagnosed with a particular tumour

type (the cases, typically numbering several hundred) and an equal number of persons of the

same age, sex (where relevant), racial background, and social situation (the controls). Both

cases and controls are then assessed in respect of their exposure to particular chemicals some

decades earlier, as best each individual may recall.


http://monographs.iarc.fr/


32

If the cases were, as a group, more frequently exposed or exposed to a greater extent to the

chemical of interest than the controls, increased carcinogenic risk associated with such

exposure.

In studies referred to as either prospective or cohort studies, circumstances specifically

including known exposure to particular chemicals are documented for a large number of

individuals (typically numbering a million or more). After 15, 20 or many more years,

persons in this sub-population diagnosed with particular cancers are identified. Risk of cancer

may be inferred from such information. A ‘nested’ case-control study may involve those

diagnosed with a particular cancer and then identifying persons in the original sub-population

who have not been diagnosed with cancer, matched as described for ‘controls’ in the

paragraph above. Review of records will then establish whether the persons diagnosed with

cancer are more exposed to any particular chemicals. Increased risk of cancer may then be

associated with exposure to those chemicals.

In general, greater confidence that a chemical may cause cancer in humans is vested in

findings from prospective studies than from case-control studies since the former are not

subject to what is termed ‘recall bias’: the scenario in which a cancer patient is more

conscious of contact with chemicals than is a control.



33

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Documents

An evaluation of the plausibility that exposure to certain