Revised June 2009Revised June 2009

QUEEN'S UNIVERSITY BELFASTQUEEN'S UNIVERSITY BELFAST

GUIDELINES FOR WORK WITH CHEMICAL CARCINOGENSGUIDELINES FOR WORK WITH CHEMICAL CARCINOGENS

1.1. INTRODUCTIONINTRODUCTION

Cancer is the generic name for a group of diseases that affect humankind, animals and plants. InCancer is the generic name for a group of diseases that affect humankind, animals and plants. In humans, almost every organ in the body can be affected. It is a disease in which some of the cells ofhumans, almost every organ in the body can be affected. It is a disease in which some of the cells of the body have an unlimited power of disordered reproduction and show some loss of structuralthe body have an unlimited power of disordered reproduction and show some loss of structural differentiation. This usually results in the formation of malignant tumours, which are non-differentiation. This usually results in the formation of malignant tumours, which are non-encapsulated (i.e. not benign) and which are able to invade other parts of the body to form secondaryencapsulated (i.e. not benign) and which are able to invade other parts of the body to form secondary tumours or metastases that are commonly responsible for death.tumours or metastases that are commonly responsible for death.

In the UK on average each year from 1996 to 2000 there were more than 150,000 cancer deaths,In the UK on average each year from 1996 to 2000 there were more than 150,000 cancer deaths, making it second only to coronary heart disease as a major cause of death. Worldwide, it has beenmaking it second only to coronary heart disease as a major cause of death. Worldwide, it has been estimated that in excess of ten million new cases of cancer are diagnosed each year. These casesestimated that in excess of ten million new cases of cancer are diagnosed each year. These cases are split almost equally between the developed and developing world. It has also been estimated thatare split almost equally between the developed and developing world. It has also been estimated that cancer accounts for 40% of all deaths in the age range 20-64 years (i.e. the typical working years ofcancer accounts for 40% of all deaths in the age range 20-64 years (i.e. the typical working years of life).life).

Although this disorder remains far from well characterised, three environmental risk factors areAlthough this disorder remains far from well characterised, three environmental risk factors are implicated in the development of cancers : exposure to radiation, exposure to chemicals and exposureimplicated in the development of cancers : exposure to radiation, exposure to chemicals and exposure to biological agents. Also included are risk factors related to personal behaviour (in particularto biological agents. Also included are risk factors related to personal behaviour (in particular smoking and certain dietary factors) and to occupation. Since the time delay between first exposuresmoking and certain dietary factors) and to occupation. Since the time delay between first exposure to a carcinogenic agent and the onset of symptoms can vary from 5 to 40 years, it is extremely difficultto a carcinogenic agent and the onset of symptoms can vary from 5 to 40 years, it is extremely difficult to establish in retrospect the proportion of cancers attributable solely to occupational exposure.to establish in retrospect the proportion of cancers attributable solely to occupational exposure. However, this proportion is likely to be small. Sir Richard Doll estimated (1992) that about 4% (up toHowever, this proportion is likely to be small. Sir Richard Doll estimated (1992) that about 4% (up to maximum of 6%) of cancer deaths are occupationally related compared with 33-35% and 10-60% ofmaximum of 6%) of cancer deaths are occupationally related compared with 33-35% and 10-60% of cancer deaths related to tobacco and dietary factors respectively.cancer deaths related to tobacco and dietary factors respectively.

Irrespective of the "actual" proportion of cancers attributable to occupational exposure to known orIrrespective of the "actual" proportion of cancers attributable to occupational exposure to known or putative carcinogenic agents, it is widely accepted that they are largely avoidable by the adoption ofputative carcinogenic agents, it is widely accepted that they are largely avoidable by the adoption of good occupational practices.good occupational practices.

It is considered that if the practices set out in this guidance note are scrupulously adhered to, theIt is considered that if the practices set out in this guidance note are scrupulously adhered to, the potential risk to health from the use of carcinogenic agents in the laboratory should be reduced to apotential risk to health from the use of carcinogenic agents in the laboratory should be reduced to a level well below that commonly and unquestioningly accepted in everyday life outside the laboratorylevel well below that commonly and unquestioningly accepted in everyday life outside the laboratory environment.environment.

However there is no room for complacency. Although, recent (1990-1993) retrospective studies haveHowever there is no room for complacency. Although, recent (1990-1993) retrospective studies have confirmed that the overall cancer incidence rates in laboratory workers were lower than those found inconfirmed that the overall cancer incidence rates in laboratory workers were lower than those found in the general "age-matched" population, there was also a suggestion of elevated rates for certain typesthe general "age-matched" population, there was also a suggestion of elevated rates for certain types of cancer, notably lymphatic and haematopoietic cancers.of cancer, notably lymphatic and haematopoietic cancers.

1.11.1 Carcinogenic AgentsCarcinogenic Agents

Although the vast majority of recognised occupational carcinogens are chemical substances, variousAlthough the vast majority of recognised occupational carcinogens are chemical substances, various physical agents and some biological agents are capable of inducing cancer.physical agents and some biological agents are capable of inducing cancer.

1.21.2 Chemical CarcinogensChemical Carcinogens

This group includes reactive substances that are capable of directly binding to and mutating cellularThis group includes reactive substances that are capable of directly binding to and mutating cellular DNA e.g. bis (chloromethyl) ether, dimethyl sulphate; inert substances which are metabolised by theDNA e.g. bis (chloromethyl) ether, dimethyl sulphate; inert substances which are metabolised by the body into reactive species capable of exerting a carcinogenic effect e.g. benzo [a] pyrene isbody into reactive species capable of exerting a carcinogenic effect e.g. benzo [a] pyrene is metabolised into an epoxide and this functions as the active carcinogenic species; and substances metabolised into an epoxide and this functions as the active carcinogenic species; and substances

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which are not conveniently categorised by either chemical structure or mode of action e.g. polycyclicwhich are not conveniently categorised by either chemical structure or mode of action e.g. polycyclic aromatic hydrocarbons, aromatic amines, aromatic nitro compounds and N-nitroso compounds. aromatic hydrocarbons, aromatic amines, aromatic nitro compounds and N-nitroso compounds.

Some inorganic compounds are also known human carcinogens. These include compounds ofSome inorganic compounds are also known human carcinogens. These include compounds of arsenic, beryllium, cadmium, chromium and nickel. The mechanism of action of these largely remainsarsenic, beryllium, cadmium, chromium and nickel. The mechanism of action of these largely remains to be elucidated.to be elucidated.

1.31.3 Physical CarcinogensPhysical Carcinogens

This diverse group includes ionising and non-ionising radiation, (ultraviolet, x-rays and This diverse group includes ionising and non-ionising radiation, (ultraviolet, x-rays and -radiation)-radiation) and irritants such as hard wood dust and asbestos. Whilst the damaging effects of both types ofand irritants such as hard wood dust and asbestos. Whilst the damaging effects of both types of radiation can be linked to chemical modification of cellular DNA, the mode of action of other physicalradiation can be linked to chemical modification of cellular DNA, the mode of action of other physical carcinogens is less well understood.carcinogens is less well understood.

1.41.4 Biological CarcinogensBiological Carcinogens

Viral Agents: The proportion of all human cancers attributable to viral agents has proved difficult toViral Agents: The proportion of all human cancers attributable to viral agents has proved difficult to assess as the evidence is generally less conclusive than that for physical and chemical agents.assess as the evidence is generally less conclusive than that for physical and chemical agents. However, some associations have been clearly established. For example, the Epstein-Barr virus canHowever, some associations have been clearly established. For example, the Epstein-Barr virus can cause Burkitt's lymphoma in a subject whose immune system is stressed by malarial infection; acause Burkitt's lymphoma in a subject whose immune system is stressed by malarial infection; a human papilloma virus, which normally causes genital warts has been implicated as the cause ofhuman papilloma virus, which normally causes genital warts has been implicated as the cause of cervical cancer; and hepatitis B infection has been found to induce cancer of the liver.cervical cancer; and hepatitis B infection has been found to induce cancer of the liver.

Oncogene: This is a gene either present in a cell or carried by a virus (usually a homologue of theOncogene: This is a gene either present in a cell or carried by a virus (usually a homologue of the cellular oncogene) capable of progressing cells through a stage in the multistage cancer process.cellular oncogene) capable of progressing cells through a stage in the multistage cancer process. The Advisory Committee on Genetic Modification (ACGM) defines oncogenic DNA sequences asThe Advisory Committee on Genetic Modification (ACGM) defines oncogenic DNA sequences as those which induce tumours in experimental animals or which cause transformation of cells in vitrothose which induce tumours in experimental animals or which cause transformation of cells in vitro leading to an escape from normal growth control, immortalisation of cells or induce anchorageleading to an escape from normal growth control, immortalisation of cells or induce anchorage independent growth.independent growth.

In this Guidance Note only laboratory work with chemical carcinogens is considered. Those intendingIn this Guidance Note only laboratory work with chemical carcinogens is considered. Those intending to work with ionising or non-ionising radiation should consult Departmental local rules and seek adviceto work with ionising or non-ionising radiation should consult Departmental local rules and seek advice from their local Radiation Protection Supervisor and the University Radiation Protection Advisor.from their local Radiation Protection Supervisor and the University Radiation Protection Advisor. Others intending to work with oncogenes are referred to the publication, ACGM/HSEOthers intending to work with oncogenes are referred to the publication, ACGM/HSEGuidance Note 1: Guidance on construction of recombinants containing potentially oncogenic nucleicGuidance Note 1: Guidance on construction of recombinants containing potentially oncogenic nucleic acid sequences and should seek further guidance from their local Biological Safety Officer and theacid sequences and should seek further guidance from their local Biological Safety Officer and the University Biological Safety Advisor.University Biological Safety Advisor.

2.2. RECOGNITION OF CHEMICAL CARCINOGENSRECOGNITION OF CHEMICAL CARCINOGENS

In Reg 2(1) of The Control of Substances Hazardous to Health Regs (NI) 2003 ("COSHH") aIn Reg 2(1) of The Control of Substances Hazardous to Health Regs (NI) 2003 ("COSHH") a carcinogen is defined as:carcinogen is defined as:

(a)(a) any substance or preparation, which when classified in accordance with the classificationany substance or preparation, which when classified in accordance with the classification provided for by Reg 4 of the Chemicals (Hazard Information and Packaging) Regs (NI) 2002provided for by Reg 4 of the Chemicals (Hazard Information and Packaging) Regs (NI) 2002 ("CHiP"), would be in the category of danger, carcinogenic (category 1) or carcinogenic("CHiP"), would be in the category of danger, carcinogenic (category 1) or carcinogenic (category 2) whether or not the substance or preparation would be required to be classified(category 2) whether or not the substance or preparation would be required to be classified under those Regs;under those Regs;

These regulations have been replaced by the Chemicals (Hazard Information and PackagingThese regulations have been replaced by the Chemicals (Hazard Information and Packaging for Supply) Regs 2009. The Approved Supply List has been discontinued. The list offor Supply) Regs 2009. The Approved Supply List has been discontinued. The list of harmonised classifications and labelling requirements have been incorporated into Table 3.2harmonised classifications and labelling requirements have been incorporated into Table 3.2 of Part 3 of Annex VI of the CLP Regulation;of Part 3 of Annex VI of the CLP Regulation;

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(b)(b) any substance or preparation listed in Schedule 1 and any substance or preparation arisingany substance or preparation listed in Schedule 1 and any substance or preparation arising from a process specified in that Schedule which is a substance hazardous to health.from a process specified in that Schedule which is a substance hazardous to health.

Chemical substances which currently meet that definition are listed in Appendices 1, 2 and 3Chemical substances which currently meet that definition are listed in Appendices 1, 2 and 3 (respectively).(respectively).

It should be noted that under the CHiP Regs substances may be classified carcinogenic, mutagenic orIt should be noted that under the CHiP Regs substances may be classified carcinogenic, mutagenic or toxic to reproduction (formerly teratogenic) or combinations thereof. In addition these classificationstoxic to reproduction (formerly teratogenic) or combinations thereof. In addition these classifications are subdivided into 3 categories with corresponding risk phrases, (R45, R49 etc). For example,are subdivided into 3 categories with corresponding risk phrases, (R45, R49 etc). For example, carcinogenic substances are categorised as follows.carcinogenic substances are categorised as follows.

Category 1 (R45, may cause cancer and R49, may cause cancer by inhalation)Category 1 (R45, may cause cancer and R49, may cause cancer by inhalation)

- substances known to be carcinogenic to humans. There is sufficient epidemiological evidence to- substances known to be carcinogenic to humans. There is sufficient epidemiological evidence to establish a causal association between human exposure and the development of a cancer.establish a causal association between human exposure and the development of a cancer.

Category 2 (R45 and R49)Category 2 (R45 and R49)

- substances which should be regarded as carcinogenic to humans. The classification is based on- substances which should be regarded as carcinogenic to humans. The classification is based on appropriate long-term animal studies and other relevant information.appropriate long-term animal studies and other relevant information.

Category 3 (R40, little evidence of a carcinogenic effect)Category 3 (R40, little evidence of a carcinogenic effect)

- substances which may be carcinogenic to humans. This category includes substances, which have- substances which may be carcinogenic to humans. This category includes substances, which have been fully tested and which have failed to display sufficient carcinogenicity for a Category 2been fully tested and which have failed to display sufficient carcinogenicity for a Category 2 classification, as well as substances which have not been fully investigated.classification, as well as substances which have not been fully investigated.

Although Category 3 carcinogenic substances and substances, which have been classified asAlthough Category 3 carcinogenic substances and substances, which have been classified as exclusively mutagenic (Muta) or toxic to reproduction (Repr) (Appendices 4, 5 & 6) are not included inexclusively mutagenic (Muta) or toxic to reproduction (Repr) (Appendices 4, 5 & 6) are not included in the COSHH definition of "carcinogen", work with these substances should be controlled in accordancethe COSHH definition of "carcinogen", work with these substances should be controlled in accordance with this guidance note.with this guidance note.

Therefore it must be stressed that the substances in Appendices 1 - 6 Therefore it must be stressed that the substances in Appendices 1 - 6 do notdo not represent a definitive list represent a definitive list of chemical carcinogens. Of the 100,000 chemical substances registered in The European Inventoryof chemical carcinogens. Of the 100,000 chemical substances registered in The European Inventory of Existing Commercial Chemical Substances (EINECS) between 1.1.71 and 18.9.81, only a smallof Existing Commercial Chemical Substances (EINECS) between 1.1.71 and 18.9.81, only a small fraction have been fully tested for carcinogenicity and classified under CHiP. Similarly, "new"fraction have been fully tested for carcinogenicity and classified under CHiP. Similarly, "new" substances (ie those not listed in EINECS) remain to be tested and classified. To date about 3000substances (ie those not listed in EINECS) remain to be tested and classified. To date about 3000 substances have been shown to ellicit some kind of carcinogenic effect in man or animals, of whichsubstances have been shown to ellicit some kind of carcinogenic effect in man or animals, of which only 1% are universally regarded as definite human carcinogens. Obviously, the list of provenonly 1% are universally regarded as definite human carcinogens. Obviously, the list of proven chemical carcinogens will grow as results from epidemiological and other studies become available. chemical carcinogens will grow as results from epidemiological and other studies become available.

In addition, certain classes of substances (including medicines, drugs, pesticides, "new" substancesIn addition, certain classes of substances (including medicines, drugs, pesticides, "new" substances and substances either used or synthesised in research and development) are exempt fromand substances either used or synthesised in research and development) are exempt from classification under CHiP. Such substances may, however, be tested and/or classified under otherclassification under CHiP. Such substances may, however, be tested and/or classified under other schemes and legislation (Appendix 7). It is therefore vitally important to consult as many sources ofschemes and legislation (Appendix 7). It is therefore vitally important to consult as many sources of toxicological information as possible (Appendix 8) in assessing the possible carcinogenicity of a giventoxicological information as possible (Appendix 8) in assessing the possible carcinogenicity of a given substance. Unknown substances or new substances for which there is no toxicological data shouldsubstance. Unknown substances or new substances for which there is no toxicological data should be controlled as potential carcinogens until there is sufficient evidence to the contrary.be controlled as potential carcinogens until there is sufficient evidence to the contrary.

3.3. ASSESSMENT OF WORK WITH CHEMICAL CARCINOGENSASSESSMENT OF WORK WITH CHEMICAL CARCINOGENS

Under Reg 6 of COSHH, there is a requirement to conduct a 'suitable and sufficient' assessment ofUnder Reg 6 of COSHH, there is a requirement to conduct a 'suitable and sufficient' assessment of the health risks posed by work with substances hazardous to health prior to commencement of thatthe health risks posed by work with substances hazardous to health prior to commencement of that work. Advice and guidance on assessment is available from each Departmental COSHH Supervisor. work. Advice and guidance on assessment is available from each Departmental COSHH Supervisor.

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Detailed information, instruction and training in assessment is available through the University SafetyDetailed information, instruction and training in assessment is available through the University Safety Service.Service.

Although a project worker may conduct the assessment if deemed competent it is the duty of theAlthough a project worker may conduct the assessment if deemed competent it is the duty of the project supervisor to ensure that all his/her projects involving substances hazardous to health areproject supervisor to ensure that all his/her projects involving substances hazardous to health are properly assessed. (CVCP Guidance Note: Responsibilities of Supervisors towards Postgraduate andproperly assessed. (CVCP Guidance Note: Responsibilities of Supervisors towards Postgraduate and Undergraduate Students).Undergraduate Students).

In view of the insidious nature of cancer, the assessment of work with carcinogens must be rigorous.In view of the insidious nature of cancer, the assessment of work with carcinogens must be rigorous.

A rigorous assessment must be fully documented and include the following details:A rigorous assessment must be fully documented and include the following details:

-- duration and nature of the projectduration and nature of the project

-- persons at particular risk from exposure to the carcinogenpersons at particular risk from exposure to the carcinogen

-- nature and quantities of carcinogenic substances to be usednature and quantities of carcinogenic substances to be used e.g. e.g. physical state (vapour, powder, aqueous/non-aqueous solution), physicochemicalphysical state (vapour, powder, aqueous/non-aqueous solution), physicochemical

properties (volatility, lipophilic/lipophobic)properties (volatility, lipophilic/lipophobic)

-- nature, degree and route of possible exposure to the carcinogennature, degree and route of possible exposure to the carcinogen e.g. inhalation of gases/vapours, absorption of liquids/vapours through the skin or other e.g. inhalation of gases/vapours, absorption of liquids/vapours through the skin or other

mucosal surfaces, penetration of the skin, contamination of the eyes, accidentalmucosal surfaces, penetration of the skin, contamination of the eyes, accidental ingestioningestion

-- practicability of preventing exposure to the carcinogen by substitution with non-carcinogenicpracticability of preventing exposure to the carcinogen by substitution with non-carcinogenic substance or by total enclosure of the processsubstance or by total enclosure of the process e.g. e.g. use of glove-boxuse of glove-box

-- steps taken to achieve adequate control where prevention is not practicable steps taken to achieve adequate control where prevention is not practicable e.g. e.g. use of a fume cupboard, good laboratory practiceuse of a fume cupboard, good laboratory practice

-- use of personal protective equipmentuse of personal protective equipment e.g. e.g. laboratory coats, dust masks, gloves etc.laboratory coats, dust masks, gloves etc.

-- precautions to be adopted in an emergency precautions to be adopted in an emergency e.g e.g spills, fume cupboard failurespills, fume cupboard failure

-- safe storage and eventual disposal of the carcinogensafe storage and eventual disposal of the carcinogen

-- arrangements for monitoring exposure (below)arrangements for monitoring exposure (below)

-- arrangements for health surveillance (below)arrangements for health surveillance (below)

-- information, instruction, training and supervision arrangements for those involved in storage,information, instruction, training and supervision arrangements for those involved in storage, handling or use of carcinogenic substanceshandling or use of carcinogenic substances

-- assessment review periodassessment review period

3.13.1 Monitoring ExposureMonitoring Exposure

Routine exposure monitoring should not be necessary for most research projects provided that theRoutine exposure monitoring should not be necessary for most research projects provided that the reliability and suitability of chosen control measures are carefully considered and the controlreliability and suitability of chosen control measures are carefully considered and the control measures are properly used and maintained. Further information about monitoring may be obtainedmeasures are properly used and maintained. Further information about monitoring may be obtained from the University Safety Service.from the University Safety Service.

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3.23.2 Health SurveillanceHealth Surveillance

Health Surveillance is appropriate for all persons working with carcinogens unless their exposure toHealth Surveillance is appropriate for all persons working with carcinogens unless their exposure to the carcinogens is not significant. Therefore, all projects likely to entail significant exposure tothe carcinogens is not significant. Therefore, all projects likely to entail significant exposure to carcinogenic substances should be referred to the Occupational Health Physician, Occupationalcarcinogenic substances should be referred to the Occupational Health Physician, Occupational Health, by the project supervisor.Health, by the project supervisor.

3.33.3 Prohibited SubstancesProhibited Substances

Finally, it should be noted that work with the following chemical carcinogens is Finally, it should be noted that work with the following chemical carcinogens is prohibitedprohibited under Reg under Reg 4 of COSHH: 2-naphthylamine, benzidine, 4-aminodiphenyl, 4-nitrodiphenyl, their salts and4 of COSHH: 2-naphthylamine, benzidine, 4-aminodiphenyl, 4-nitrodiphenyl, their salts and substances containing the above compounds in a total concentration exceeding 0.1%. Only thesubstances containing the above compounds in a total concentration exceeding 0.1%. Only the Health and Safety Executive may grant exemptions to these prohibitions.Health and Safety Executive may grant exemptions to these prohibitions.

4.4. PREVENTION AND/OR CONTROL OF EXPOSURE TO CHEMICAL CARCINOGENSPREVENTION AND/OR CONTROL OF EXPOSURE TO CHEMICAL CARCINOGENS

Under Regulation 7(5) of COSHH, if it is not reasonably practicable to prevent exposure toUnder Regulation 7(5) of COSHH, if it is not reasonably practicable to prevent exposure to carcinogens by using alternative substances or processes, then adequate control of exposure to thecarcinogens by using alternative substances or processes, then adequate control of exposure to the carcinogen must be achieved by application of carcinogen must be achieved by application of allall of the following measures: of the following measures:

-- totally enclose the process and handling systems unless this is not reasonably practicabletotally enclose the process and handling systems unless this is not reasonably practicable e.g. e.g. use a glove-boxuse a glove-box

-- minimise generation of, or suppress and contain, spills, leaks, dusts and vapours fromminimise generation of, or suppress and contain, spills, leaks, dusts and vapours from carcinogens by partially enclosing the process and handling systems and using local exhuastcarcinogens by partially enclosing the process and handling systems and using local exhuast ventilationventilation e.g. e.g. work in a fume cupboard. Minimise aerosol production by avoiding, if possible, use ofwork in a fume cupboard. Minimise aerosol production by avoiding, if possible, use of

blenders, sonicators, vigorous mixing or shaking. Avoid grinding operations whichblenders, sonicators, vigorous mixing or shaking. Avoid grinding operations which generate dust. Use spill trays. Fit cold traps to vacuum lines.generate dust. Use spill trays. Fit cold traps to vacuum lines.

In addition, minimise the risk of exposure to carcinogens (via absorption through the skin,In addition, minimise the risk of exposure to carcinogens (via absorption through the skin, accidental ingestion and accidental injection) by wearing the appropriate personal protectiveaccidental ingestion and accidental injection) by wearing the appropriate personal protective equipment, by prohibiting mouth pipetting, by avoiding the use of sharps and by covering allequipment, by prohibiting mouth pipetting, by avoiding the use of sharps and by covering all cuts and abrasions.cuts and abrasions.

-- limit the quantities of carcinogens usedlimit the quantities of carcinogens used e.g. e.g. consider reaction scales. Keep stocks accurately but to a minimumconsider reaction scales. Keep stocks accurately but to a minimum

-- minimise the number of persons who may be exposed to carcinogensminimise the number of persons who may be exposed to carcinogens

e.g. e.g. restrict access to the laboratory to authorised personnel onlyrestrict access to the laboratory to authorised personnel only

-- prohibit eating, drinking, smoking and the use of cosmetics in areas that may beprohibit eating, drinking, smoking and the use of cosmetics in areas that may be contaminated with carcinogens. Exclude personal items (coats, bags, radios etc.) whichcontaminated with carcinogens. Exclude personal items (coats, bags, radios etc.) which would be difficult to decontaminate.would be difficult to decontaminate.

-- provide and maintain adequate hygiene measures, both general and personalprovide and maintain adequate hygiene measures, both general and personal

-- designate those areas and installations which may be contaminated by carcinogens, and usedesignate those areas and installations which may be contaminated by carcinogens, and use suitable and sufficient warning signssuitable and sufficient warning signs

-- store, handle and dispose of carcinogens safely. Carcinogens should be stored in tightlystore, handle and dispose of carcinogens safely. Carcinogens should be stored in tightly sealed and appropriately labelled containers. They should be segregated from othersealed and appropriately labelled containers. They should be segregated from other substances when not in use and should be stored securely in appropriately labelledsubstances when not in use and should be stored securely in appropriately labelled refrigerators, cupboards or rooms. Safe disposal of carcinogens should be arranged with therefrigerators, cupboards or rooms. Safe disposal of carcinogens should be arranged with the University Safety Service.University Safety Service.

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The application and use of the above control measures in work with carcinogens should beThe application and use of the above control measures in work with carcinogens should be incorporated into a written protocol, or local rules which contain standard operating procedures andincorporated into a written protocol, or local rules which contain standard operating procedures and give details of good laboratory safe working practices. Written protocols should be presented to thegive details of good laboratory safe working practices. Written protocols should be presented to the appropriate School Safety Committee for approval prior to commencement of the work.appropriate School Safety Committee for approval prior to commencement of the work.

5.5. MANAGEMENT OF WORK WITH CARCINOGENSMANAGEMENT OF WORK WITH CARCINOGENS

It is the supervisor's responsibility to ensure that his/her research workers receive adequateIt is the supervisor's responsibility to ensure that his/her research workers receive adequate information, instruction and training. Workers should be aware of the risks to health involved in theinformation, instruction and training. Workers should be aware of the risks to health involved in the work and the importance of using all the requisite control measures correctly.work and the importance of using all the requisite control measures correctly.It is also the supervisor's responsibility to ensure that the workers are following agreed proceduresIt is also the supervisor's responsibility to ensure that the workers are following agreed procedures and written protocols or working to agreed local rules.and written protocols or working to agreed local rules.Workers must not deviate from documented procedures or stray beyond the limits of the projectWorkers must not deviate from documented procedures or stray beyond the limits of the project without the supervisor's knowledge or consent.without the supervisor's knowledge or consent.

6.6. REFERENCESREFERENCES

Approved Code of Practice : Control of substances hazardous to health, 5th Edition, HSEApproved Code of Practice : Control of substances hazardous to health, 5th Edition, HSE

Hazardous Substances : Carcinogens Guide, CronerHazardous Substances : Carcinogens Guide, Croner

Occupational Carcinogens : Croner's Health and Safety Special Report 1994Occupational Carcinogens : Croner's Health and Safety Special Report 1994

EH40/0X Workplace Exposure Limits 200X, HSEEH40/0X Workplace Exposure Limits 200X, HSE

COSHH: Guidance for universities, polytechnics and colleges of further and higher education: COSHH: Guidance for universities, polytechnics and colleges of further and higher education: Education Services Advisory Committee, HSCEducation Services Advisory Committee, HSC

Laboratory Work with Chemical Carcinogens and Oncogenes, Specialist Inspector Reports No. 41, Laboratory Work with Chemical Carcinogens and Oncogenes, Specialist Inspector Reports No. 41, HSEHSE

Health and Safety Responsibilities of Supervisors towards Postgraduate and Undergraduate StudentsHealth and Safety Responsibilities of Supervisors towards Postgraduate and Undergraduate Students CVCPCVCP

Prepared by: Dr John Wilson, Radiation Protection Advisor/Occupational HygienistPrepared by: Dr John Wilson, Radiation Protection Advisor/Occupational HygienistApproved by: Chemical Agents Advisory CommitteeApproved by: Chemical Agents Advisory Committee

APPENDIX 1APPENDIX 1 CATEGORY 1CATEGORY 1 CARCINOGENSCARCINOGENS

Category 1 Carcinogens: R45 May cause cancerCategory 1 Carcinogens: R45 May cause cancer

4-aminobiphenyl and its salts4-aminobiphenyl and its saltsarsenic acid and its saltsarsenic acid and its saltsarsenic pentoxidearsenic pentoxidearsenic trioxidearsenic trioxideasbestosasbestosbenzene (+ Muta Cat 2)benzene (+ Muta Cat 2)benzidine and its acetate, dihydrochloride, sulphate saltsbenzidine and its acetate, dihydrochloride, sulphate saltsbis (chloromethyl) ether bis (chloromethyl) ether i.e. BCMEi.e. BCME1,3 – butadiene1,3 – butadienebutane containing butane containing >> 0.1% butadiene, isobutane containing 0.1% butadiene, isobutane containing >> 0.1% butadiene 0.1% butadienechloromethyl methyl ether (usually contaminated with BCME) chloromethyl methyl ether (usually contaminated with BCME) erioniteerionitelead hydrogen arsenate (+Repr. Cat 1 +Repr Cat 3)lead hydrogen arsenate (+Repr. Cat 1 +Repr Cat 3)2-naphthylamine and its acetate and hydrochloride salts2-naphthylamine and its acetate and hydrochloride saltspetroleum gases and substances (unrefined or mildly refined base oil)petroleum gases and substances (unrefined or mildly refined base oil)triethylarsenatetriethylarsenatevinyl chloridevinyl chloridezinc chromates, including zinc potassium chromatezinc chromates, including zinc potassium chromate

Category 1 Carcinogens: R49 May cause cancer by inhalationCategory 1 Carcinogens: R49 May cause cancer by inhalation

chromium trioxide (+ Muta Cat 2, + Repr Cat 3)chromium trioxide (+ Muta Cat 2, + Repr Cat 3)dinickel trioxidedinickel trioxidenickel dioxidenickel dioxidenickel monoxidenickel monoxidenickel subsulphidenickel subsulphidenickel sulphidenickel sulphide

*Additional classifications:*Additional classifications: Repr - Toxic to ReproductionRepr - Toxic to ReproductionMuta - MutagenicMuta - MutagenicCat - Category number 1,2 or 3Cat - Category number 1,2 or 3

APPENDIX 2 APPENDIX 2 CATEGORY 2CATEGORY 2 CARCINOGENSCARCINOGENS

Category 2 Carcinogens : R45 May cause cancerCategory 2 Carcinogens : R45 May cause cancer

acrylamide (+ Muta Cat 2, Repr Cat 3)acrylamide (+ Muta Cat 2, Repr Cat 3)acrylonitrileacrylonitrile4-aminoazobenzene4-aminoazobenzene2-amino-5-azotoluene2-amino-5-azotoluene4-amino-3-fluorophenol4-amino-3-fluorophenolp-aminophenylether and its salts (+ Muta Cat 2, + Repr Cat 3)p-aminophenylether and its salts (+ Muta Cat 2, + Repr Cat 3)ammonium dichromate (+ Muta Cat 2, + Repr Cat 2)ammonium dichromate (+ Muta Cat 2, + Repr Cat 2)aziridine (+ Muta Cat 2)aziridine (+ Muta Cat 2)azobenzene (+ Muta Cat 3)azobenzene (+ Muta Cat 3)Basic Red 9Basic Red 9Basic Violet 3 (> 0.1% of Michler’s ketone)Basic Violet 3 (> 0.1% of Michler’s ketone)benzidine based azo dyesbenzidine based azo dyesbenz(e) acephenanthyrlenebenz(e) acephenanthyrlenebenzo [a] anthracenebenzo [a] anthracenebenzo [b] fluoranthenebenzo [b] fluoranthenebenzo[j] fluoranthenebenzo[j] fluoranthenebenzo [k] fluoranthenebenzo [k] fluoranthenebenzo [a] pyrene (+ Muta Cat 2, Repr Cat 2) benzo [a] pyrene (+ Muta Cat 2, Repr Cat 2) benzo [e] pyrenebenzo [e] pyrenebenzyl chloridebenzyl chloride2,2’-bioxirane (+ Muta Cat 2)2,2’-bioxirane (+ Muta Cat 2)4,4'-bis (dimethylamino) benzophenone (+ Muta Cat 3), Michler’s keton4,4'-bis (dimethylamino) benzophenone (+ Muta Cat 3), Michler’s ketoncadmium chloride (+ Muta Cat 2, Repr Cat 2)cadmium chloride (+ Muta Cat 2, Repr Cat 2)cadmium oxide (+ Muta Cat 2, + Repr Cat 2)cadmium oxide (+ Muta Cat 2, + Repr Cat 2)cadmium sulphate (+ Muta Cat 2, + Repr Cat 2)cadmium sulphate (+ Muta Cat 2, + Repr Cat 2)cadmium sulphide (+ Muta Cat 2, + Repr Cat 2)cadmium sulphide (+ Muta Cat 2, + Repr Cat 2)cadmium fluoride (+ Muta Cat 2, Repr Cat 2)cadmium fluoride (+ Muta Cat 2, Repr Cat 2)calcium chromatecalcium chromatecaptafolcaptafolcarbadoxcarbadox4-chloroaniline4-chloroanilinep-chlorobenzotrichloride (+ Repr Cat 3)p-chlorobenzotrichloride (+ Repr Cat 3)chloroprenechloroprene4-chloro-o-toluidine and its hydrochloride (+ Muta Cat 3)4-chloro-o-toluidine and its hydrochloride (+ Muta Cat 3)chromium III chromatechromium III chromatechyrsene (+ Muta Cat 3)chyrsene (+ Muta Cat 3)coal tar productscoal tar productsp-cresidinep-cresidine2,4-diaminoanisole and its sulphate (+Muta Cat 3)2,4-diaminoanisole and its sulphate (+Muta Cat 3)4,4'-diaminodiphenylmethane (+ Muta Cat 3)4,4'-diaminodiphenylmethane (+ Muta Cat 3)2,4-diaminotoluene2,4-diaminotolueneo-dianisidine, its salts, azo based dyeso-dianisidine, its salts, azo based dyesdiazomethanediazomethanedibenz [a,h] anthracenedibenz [a,h] anthracene1,2-dibromo-3-chloropropane (+ Muta Cat 2, Repr Cat 1)1,2-dibromo-3-chloropropane (+ Muta Cat 2, Repr Cat 1)1,2-dibromoethane1,2-dibromoethane2,3 dibromo-1-propanol (+Repr Cat 3)2,3 dibromo-1-propanol (+Repr Cat 3)3,3'-dichlorobenzidine and its salts3,3'-dichlorobenzidine and its salts1,4-dichlorobut-2-ene1,4-dichlorobut-2-ene1,3-dichloro-2-propanol1,3-dichloro-2-propanoldiethyl sulphate (+ Muta Cat 2)diethyl sulphate (+ Muta Cat 2)dimethylcarbamoyl chloridedimethylcarbamoyl chloride1,1-dimethylhydrazine1,1-dimethylhydrazine1,2-dimethylhydrazine1,2-dimethylhydrazinedimethylnitrosaminedimethylnitrosaminedimethylsulfamoyl chloridedimethylsulfamoyl chloride

(ii)(ii)APPENDIX 2 (continued)APPENDIX 2 (continued)

dimethyl sulphate (+ Muta Cat 3)dimethyl sulphate (+ Muta Cat 3)2,3-dinitrotoluene (+ Muta Cat 2, Repr Cat 3)2,3-dinitrotoluene (+ Muta Cat 2, Repr Cat 3)2,4-dinitrotoluene (+ Muta Cat 2, Repr Cat 3)2,4-dinitrotoluene (+ Muta Cat 2, Repr Cat 3)2,5-dinitrotoluene (+ Muta Cat 3, Repr Cat 3)2,5-dinitrotoluene (+ Muta Cat 3, Repr Cat 3)2,6-dinitrololuene (+ Muta Cat 2, Repr Cat 3)2,6-dinitrololuene (+ Muta Cat 2, Repr Cat 3)3,4-dinitrololuene (+ Muta Cat 3, Repr Cat 3)3,4-dinitrololuene (+ Muta Cat 3, Repr Cat 3)3,5-dinitrololuene (+ Muta Cat 3, Repr Cat 3)3,5-dinitrololuene (+ Muta Cat 3, Repr Cat 3)Direct Black 38 (+ Repr Cat 3)Direct Black 38 (+ Repr Cat 3)Direct Blue 6 (+ Repr Cat 3)Direct Blue 6 (+ Repr Cat 3)Direct brown 95Direct brown 95Direct Red 28 (+ Repr Cat 3)Direct Red 28 (+ Repr Cat 3)Disperse Blue 1Disperse Blue 1epichlorohydrinepichlorohydrin2,3-epoxypropan-1-ol (+ Muta Cat 3, Repr Cat 2)2,3-epoxypropan-1-ol (+ Muta Cat 3, Repr Cat 2)1,2 epoxy propane-3-phenoxy propane (+ Muta Cat 3)1,2 epoxy propane-3-phenoxy propane (+ Muta Cat 3)ethylene dibromideethylene dibromideethylene dichlorideethylene dichlorideethylene oxide (+ Muta Cat 2)ethylene oxide (+ Muta Cat 2)furan (+ Muta Cat 3)furan (+ Muta Cat 3)hexachlorobenzenehexachlorobenzenehexamethylphosphoramide (+ Muta Cat 2)hexamethylphosphoramide (+ Muta Cat 2)hydrazine and its saltshydrazine and its saltshydrazine bis (3-carboxy-4-hydroxybenzenesulphonate)hydrazine bis (3-carboxy-4-hydroxybenzenesulphonate)hydrazine trinitromethanehydrazine trinitromethanehydrazobenzenehydrazobenzene6-hydroxy-1-(3-isopropoxy propyl)-4-methyl-2-oxo-5-[4-(phenylazo)phenylazo]-1,2-dihydro-3- 6-hydroxy-1-(3-isopropoxy propyl)-4-methyl-2-oxo-5-[4-(phenylazo)phenylazo]-1,2-dihydro-3- pyridinecarbonitrile pyridinecarbonitrile(6-(4-dhyroxy-3-(2-methoxyphenylazo)-2-sulphonato-7-naphthylamino)-1,3,5-triazin-2,4-(6-(4-dhyroxy-3-(2-methoxyphenylazo)-2-sulphonato-7-naphthylamino)-1,3,5-triazin-2,4-diyl)bis[(amino-1-diyl)bis[(amino-1- methylethyl) ammonium] formate methylethyl) ammonium] formateisobutyl nitrite (+ muta Cat 3)isobutyl nitrite (+ muta Cat 3)2-methoxyaniline (+ Muta Cat 3)2-methoxyaniline (+ Muta Cat 3)methoxy-m-phenylenediamine (+ Muta Cat 3)methoxy-m-phenylenediamine (+ Muta Cat 3)methylacrylamidomethoxy acetate (containing) methylacrylamidomethoxy acetate (containing) 0.1% acrylamide) (+ Muta Cat 2) 0.1% acrylamide) (+ Muta Cat 2)methylacrylamidoglycolate (containing methylacrylamidoglycolate (containing 0.1% acrylamide (+ Muta Cat 2) 0.1% acrylamide (+ Muta Cat 2)2-methylaziridine2-methylaziridinemethylazoxymethanol acetate (+ Repr Cat 2)methylazoxymethanol acetate (+ Repr Cat 2)4-methylbenzene-sulphonate(s)-oxiranemethanol (+ Muta Cat 3)4-methylbenzene-sulphonate(s)-oxiranemethanol (+ Muta Cat 3)4,4'-methylenebis (2-chloroaniline) and its salts4,4'-methylenebis (2-chloroaniline) and its salts4,4'-methylene-di-o-toluidine4,4'-methylene-di-o-toluidine1-methyl-3-nitro-1-nitrosoguanidine1-methyl-3-nitro-1-nitrosoguanidine5-nitroacenophthene5-nitroacenophthene2-nitroanisole2-nitroanisole4-nitrobiphenyl4-nitrobiphenylnitrofen (+ Repr Cat 2)nitrofen (+ Repr Cat 2)2-nitronaphthalene2-nitronaphthalene2-nitropropane2-nitropropanenitrosodiethanolaminenitrosodiethanolaminenitrosodimethylaminenitrosodimethylamine2,22,211-(nitrosoimino) bisethanol-(nitrosoimino) bisethanolnitrosodipropylaminenitrosodipropylamine2-nitrotoluene (+ Muta Cat 2, Repr Cat 3)2-nitrotoluene (+ Muta Cat 2, Repr Cat 3)Petroleum Distillation ProductsPetroleum Distillation Productsphenylhydrazine and its chloride and sulphate salts (+ Muta Cat 3)phenylhydrazine and its chloride and sulphate salts (+ Muta Cat 3)potassium bromatepotassium bromate1,3-propanesultone1,3-propanesultone

(iii)(iii)APPENDIX 2 (continued)APPENDIX 2 (continued)

1,3-propiolactone1,3-propiolactonepropylene oxide (+ Muta Cat 2)propylene oxide (+ Muta Cat 2)safrole (+ Muta Cat 3)safrole (+ Muta Cat 3)strontium chromatestrontium chromatestyrene oxidestyrene oxidesulfallatesulfallateN,N,N',N'-tetramethyl-4,4'-methylenedianilineN,N,N',N'-tetramethyl-4,4'-methylenedianilinethioacetamidethioacetamide4,4'thiodianiline and its salts4,4'thiodianiline and its saltso-tolidine, its salts, its azo based dyeso-tolidine, its salts, its azo based dyes2,4-toluenediammine2,4-toluenediamminetoluene-2,4-diammonium sulphatetoluene-2,4-diammonium sulphateo-toluidineo-toluidinetrichloroethylene (+ Muta Cat 3)trichloroethylene (+ Muta Cat 3)1,2,3,-trichloropropane (+ Repr Cat 2)1,2,3,-trichloropropane (+ Repr Cat 2)2,4,5-trimethylaniline and its hydrochloride2,4,5-trimethylaniline and its hydrochloride,,,,-trichlorotoluene-trichlorotolueneurethane (INN)urethane (INN)vinyl bromidevinyl bromide

Category 2 Carcinogens : R49 May cause cancer by inhalationCategory 2 Carcinogens : R49 May cause cancer by inhalation

berylliumberylliumberyllium compounds except aluminium beryllium silicateberyllium compounds except aluminium beryllium silicateberyllium oxideberyllium oxidecadmium oxide (+ Muta Cat 3, Repr Cat 3)cadmium oxide (+ Muta Cat 3, Repr Cat 3)chromic oxychloridechromic oxychloridechromium (VI) compounds except barium chromatechromium (VI) compounds except barium chromatecobalt dichloridecobalt dichloridecobalt sulphatecobalt sulphatepotassium chromate (+ Muta Cat 2)potassium chromate (+ Muta Cat 2)potassium dichromate (+ Muta Cat 2, Repr Cat 2)potassium dichromate (+ Muta Cat 2, Repr Cat 2)refractory ceramic fibresrefractory ceramic fibressodium chromate (+ Muta Cat 2, Repr Cat 2)sodium chromate (+ Muta Cat 2, Repr Cat 2)sodium dichromate and its dihydrate (+ Muta Cat 2, Repr Cat 2)sodium dichromate and its dihydrate (+ Muta Cat 2, Repr Cat 2)

APPENDIX 3APPENDIX 3 COSHH COSHH Schedule 1Schedule 1

Other substances and processes to which the definition of “carcinogen” relates.Other substances and processes to which the definition of “carcinogen” relates.

AflatoxinsAflatoxinsArsenicArsenicAuramine manufactureAuramine manufactureCalcining, sintering or smelting of nickel copper matte or acid leaching or electrorefining of roasted Calcining, sintering or smelting of nickel copper matte or acid leaching or electrorefining of roasted matte matteCoal soots, coal tar, pitch and coal tar fumesCoal soots, coal tar, pitch and coal tar fumesHard wood dustsHard wood dustsIsopropyl alcohol manufacture (strong acid process)Isopropyl alcohol manufacture (strong acid process)Leather dust (shoe manufacture)Leather dust (shoe manufacture)Magenta manufactureMagenta manufactureMustard gas (β, β’ - dichlorodiethyl sulphide)Mustard gas (β, β’ - dichlorodiethyl sulphide)Rubber fume and dust during processingRubber fume and dust during processingUsed engine oilsUsed engine oils

Polychlorodibenzodioxins:Polychlorodibenzodioxins:

2,3,7,8 – TCDD*2,3,7,8 – TCDD*1,2,3,7,8 – PeCDD1,2,3,7,8 – PeCDD1,2,3,4,7,8 – HxCDD1,2,3,4,7,8 – HxCDD1,2,3,6,7,8 – HxCDD1,2,3,6,7,8 – HxCDD1,2,3,7,8,9 – HxCDD1,2,3,7,8,9 – HxCDD1,2,3,4,6,7,8 – HpCDD1,2,3,4,6,7,8 – HpCDD

Polychlorodibenzofurans:Polychlorodibenzofurans:

2,3,7,8 – TCDF2,3,7,8 – TCDF2,3,4,7,8 – PeCDF2,3,4,7,8 – PeCDF1,2,3,7,8 – PeCDF1,2,3,7,8 – PeCDF1,2,3,4,7,8 – HxCDF1,2,3,4,7,8 – HxCDF1,2,3,7,8,9 – HxCDF1,2,3,7,8,9 – HxCDF2,3,4,6,7,8 – HxCDF2,3,4,6,7,8 – HxCDF1,2,3,4,6,7,8 – HpCDF1,2,3,4,6,7,8 – HpCDF1,2,3,4,7,8,9 – HpCDF1,2,3,4,7,8,9 – HpCDF

*Where T=tetra, Pe=penta, Hx=hexa, Hp=hepta & O=octa*Where T=tetra, Pe=penta, Hx=hexa, Hp=hepta & O=octa

APPENDIX 4APPENDIX 4 CATEGORY 3CATEGORY 3 CARCINOGENSCARCINOGENS

Category 3 Carcinogens: R40 Limited evidence of a carcinogenic effectCategory 3 Carcinogens: R40 Limited evidence of a carcinogenic effect

acetaldehydeacetaldehydeacetamideacetamidealachloralachloraldrinaldrinallyl chloride (+ Muta Cat 3)allyl chloride (+ Muta Cat 3)allyl 2,3-epoxypropylether (+ Muta Cat 3, Repr Cat 3)allyl 2,3-epoxypropylether (+ Muta Cat 3, Repr Cat 3)allyl glycidyl ether (+ Muta Cat 3, Repr Cat 3allyl glycidyl ether (+ Muta Cat 3, Repr Cat 34-aminotoluene4-aminotolueneamitroleamitroleaniline and its saltsaniline and its saltsantimony trioxideantimony trioxideANTUANTUatrazine (+ Repr Cat 3)atrazine (+ Repr Cat 3)auramine and its saltsauramine and its saltsBasic Violet 3Basic Violet 3benzal chloridebenzal chloridebenzyl chloridebenzyl chloridebenzyl violet 4Bbenzyl violet 4Bbiphenyl-2-aminebiphenyl-2-aminebromoethanebromoethane1-bromo-3,4,5-trifluorobenzene1-bromo-3,4,5-trifluorobenzene2-butanone oxime2-butanone oximebutyl 2,3-epoxypropyletherbutyl 2,3-epoxypropylethercadmium sulphidecadmium sulphidecamphechlorcamphechlorcaptancaptancarbarylcarbarylcarbon tetrachloridecarbon tetrachloridechlordanechlordanechlordeconechlordeconechlordimeform and hydrochloridechlordimeform and hydrochloridechloroalkanes Cchloroalkanes C1010 – C – C1313

chloroacetaldehydechloroacetaldehydechloroethanechloroethanechloroformchloroform1-chloro-4-nitrobenzene1-chloro-4-nitrobenzenechlorotoluron (+Repr Cat 3)chlorotoluron (+Repr Cat 3)chlozolinatechlozolinatedaminozidedaminozideDDTDDTdi-allatedi-allate2,2-dibromo-2-nitroethanol2,2-dibromo-2-nitroethanol1,4-dichlorobenzene1,4-dichlorobenzene(+/-)2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl) propyl-1,1,2,2-tetrafluoroethylether(+/-)2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl) propyl-1,1,2,2-tetrafluoroethyletherdichloroacetylenedichloroacetylenedichloromethanedichloromethanedieldrindieldrindiethylcarbamoyl chloridediethylcarbamoyl chloridedihydroxybenzenedihydroxybenzene4-(4-(1,3-dihydroxyprop-2-yl) phenylamino)-1,8-dihydroxy-5-nitroanthraquinone4-(4-(1,3-dihydroxyprop-2-yl) phenylamino)-1,8-dihydroxy-5-nitroanthraquinoneN,N-dimethylanilineN,N-dimethylaniline2,6-dimethylaniline2,6-dimethylanilineN,N-dimethylanilinium tetrakis (pentafluorophenyl) borateN,N-dimethylanilinium tetrakis (pentafluorophenyl) borate3,5-dinitro-2,6-dimethyl-43,5-dinitro-2,6-dimethyl-4t t butylacetophenone (Musk ketone)butylacetophenone (Musk ketone)1,4-dioxane1,4-dioxane

(ii)(ii)APPENDIX 4 (continued)APPENDIX 4 (continued)

Disperse Yellow 3Disperse Yellow 3diurondiuronepoxiconazole (+ Repr Cat 3)epoxiconazole (+ Repr Cat 3)1,2 epoxybutane1,2 epoxybutane5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole5-ethoxy-3-trichloromethyl-1,2,4-thiadiazoleflusilazole (+ Repr Cat 2)flusilazole (+ Repr Cat 2)folpetfolpetformaldehydeformaldehyde2-furaldehyde2-furaldehydefurmecycloxfurmecycloxheptachlor and its epoxideheptachlor and its epoxidehexachlorocyclohexanehexachlorocyclohexanehydroquinone (+ Muta Cat 3)hydroquinone (+ Muta Cat 3)iprodioneiprodioneisoproturonisoproturonkresoxim-methylkresoxim-methyllead acetate (+ Repr Cat 1, Repr Cat 3)lead acetate (+ Repr Cat 1, Repr Cat 3)lead chromate (+ Repr Cat 1, Repr Cat 3)lead chromate (+ Repr Cat 1, Repr Cat 3)lead chromate molybdate sulphate red (+ Repr Cat 1, Repr Cat 3)lead chromate molybdate sulphate red (+ Repr Cat 1, Repr Cat 3)linuron (+ Repr Cat 2, Cat 3)linuron (+ Repr Cat 2, Cat 3)methyl chloridemethyl chloridemethyl iodidemethyl iodide4,4’-methylenebis (2-ethylaniline)4,4’-methylenebis (2-ethylaniline)mineral woolmineral woolMirex (+ Repr Cat 3)Mirex (+ Repr Cat 3)MolinateMolinatemonuron and monuron – TCAmonuron and monuron – TCAmorpholine-4-carbamoyl chloridemorpholine-4-carbamoyl chlorideMusk xylene (5Musk xylene (5tt butyl-2,4,6-trinitro-m-xylene) butyl-2,4,6-trinitro-m-xylene)naphthalenenaphthalene1,5 naphthalene diamine1,5 naphthalene diamineN-2-naphthylanilineN-2-naphthylaniline1-(1-naphthylmethyl) quinolinium chloride (+ Muta Cat 3)1-(1-naphthylmethyl) quinolinium chloride (+ Muta Cat 3)nickelnickelnickel carbonatenickel carbonatenickel dihydroxidenickel dihydroxidenickel sulphatenickel sulphatenickel tetracarbonyl (+ Repr Cat 2)nickel tetracarbonyl (+ Repr Cat 2)nitrobenzene (+ Repr Cat 3)nitrobenzene (+ Repr Cat 3)5-nitro-o-toluidine and its hydrochloride5-nitro-o-toluidine and its hydrochloridepentachloroethanepentachloroethanepentachlorophenol and its alkali saltspentachlorophenol and its alkali saltso-phenylenediamine and its hydrochlorideo-phenylenediamine and its hydrochlorideN-phenyl-2-naphthylamineN-phenyl-2-naphthylaminePigment Red 104 (+ Repr Cat 1, Repr Cat 3)Pigment Red 104 (+ Repr Cat 1, Repr Cat 3)Pigment Yellow 34 (+ Repr Cat 1, Repr Cat 3)Pigment Yellow 34 (+ Repr Cat 1, Repr Cat 3)PropargitePropargitepropazinepropazinepropyzamidepropyzamidepymetrazinepymetrazineresorcinol diglycidylether (+ Muta Cat 3)resorcinol diglycidylether (+ Muta Cat 3)(2RS,3RS) -3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane(2RS,3RS) -3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxiranesimazinesimazinesodium pentachlorophenate and potassium saltssodium pentachlorophenate and potassium saltssolvent yellow 14 (+ Muta Cat 3)solvent yellow 14 (+ Muta Cat 3)tetrachloroethylenetetrachloroethylene

(iii)(iii)APPENDIX 4 (continued)APPENDIX 4 (continued)

tetrachloroisophthalonitriletetrachloroisophthalonitrilethiourea (+ Repr Cat 3)thiourea (+ Repr Cat 3)TDITDIp-toluidine and chloride and sulphate saltsp-toluidine and chloride and sulphate saltstributyl phosphatetributyl phosphate2,3,4-trichlorobut-1-ene2,3,4-trichlorobut-1-ene1,1,2-trichloroethane1,1,2-trichloroethanetrichloroethylenetrichloroethylene3,5,5-trimethylcyclohex-2-enone3,5,5-trimethylcyclohex-2-enone2,4,6-trichlorophenol2,4,6-trichlorophenoltriphenyl tin and its acetate and hydroxide (+ Repr Cat 3)triphenyl tin and its acetate and hydroxide (+ Repr Cat 3)tris (2-chloroethyl) phosphatetris (2-chloroethyl) phosphatevinclozolin (+ Repr Cat 2)vinclozolin (+ Repr Cat 2)vinylidene chloridevinylidene chloride1-vinyl-2-pyrrolidone1-vinyl-2-pyrrolidone

APPENDIX 5APPENDIX 5 MUTAGENIC SUBSTANCESMUTAGENIC SUBSTANCES

Category 1: Substances known to be mutagenic to humansCategory 1: Substances known to be mutagenic to humans

R46R46 May cause heritable genetic damage.May cause heritable genetic damage.

NoneNone

Category 2: Substances which should be regarded as if they are mutagenic to humans.Category 2: Substances which should be regarded as if they are mutagenic to humans.

R46R46 May cause heritable genetic damage.May cause heritable genetic damage.

benomyl (+ Repr Cat 2)benomyl (+ Repr Cat 2)carbendazim (+ Repr Cat 2)carbendazim (+ Repr Cat 2)TGIC-triglycidyl isocyanurateTGIC-triglycidyl isocyanurate1,3,5-tris-[(2S and 2R)-2,3-epoxypropyl]-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione1,3,5-tris-[(2S and 2R)-2,3-epoxypropyl]-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione

Category 3: Substances which cause concern for humans owing to possible mutagenicCategory 3: Substances which cause concern for humans owing to possible mutagenic effects. effects.

R68R68 Possible risk of irreversible effects.Possible risk of irreversible effects.

allyl epoxypropylphenol mixturesallyl epoxypropylphenol mixtures2-aminophenol2-aminophenol4-aminophenol4-aminophenol1,3-bis (vinylsulphonylacetamido) propane1,3-bis (vinylsulphonylacetamido) propanebromomethanebromomethane2 butenal2 butenal(3-chlorophenyl)-(4-methoxy-3-nitrophenyl) methanone(3-chlorophenyl)-(4-methoxy-3-nitrophenyl) methanonecresylglycidyl ethercresylglycidyl ethercrotonaldehydecrotonaldehydecycloheximide (+ Repr Cat 2)cycloheximide (+ Repr Cat 2)2,3-dichloropropene2,3-dichloropropene5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidine)-3-fluoro-2-hydroxymethyltetrahydrofuran5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidine)-3-fluoro-2-hydroxymethyltetrahydrofuranDNOCDNOC2,3-epoxypropyl-o-tolyl ether2,3-epoxypropyl-o-tolyl ether4-ethoxyaniline4-ethoxyaniline4411-ethoxy-2-benzimidazoleanilide-ethoxy-2-benzimidazoleanilide1-ethyl-1-methylmorpholium bromide1-ethyl-1-methylmorpholium bromide1-ethyl-1-methylpyrrolidinium bromide1-ethyl-1-methylpyrrolidinium bromideFenthionFenthionGlyoxalGlyoxalhexahydrocyclopenta[c]pyrolle-1-(1H)-ammonium N-ethoxy carbonyl-N-(p-tolylsulphonyl) azanidehexahydrocyclopenta[c]pyrolle-1-(1H)-ammonium N-ethoxy carbonyl-N-(p-tolylsulphonyl) azanide(4-hydrazinophenyl)-N-methylmethanesulphonamide hydrochloride(4-hydrazinophenyl)-N-methylmethanesulphonamide hydrochloride2-(isocyanatosulphonylmethyl) benzoic acid methyl ester2-(isocyanatosulphonylmethyl) benzoic acid methyl ester2-methyl-m-phenylenediamine2-methyl-m-phenylenediaminemonocrotophosmonocrotophos4-nitrosophenol4-nitrosophenolphenolphenolm-phenylenediamine and its hydrochloridem-phenylenediamine and its hydrochloridephosphamidonphosphamidonpyrogallolpyrogallolN,N,NN,N,N11,N,N11-tetraglycidyl-4,4-tetraglycidyl-4,411diamino-3,3diamino-3,311-diethyldiphenylmethane-diethyldiphenylmethane(+/-) tetrahydrofurfuryl (R)-2-[4-(6-chloroquinoxalin-2-yloxy)phenyloxy]propionate(+ Repr Cat 2, (+/-) tetrahydrofurfuryl (R)-2-[4-(6-chloroquinoxalin-2-yloxy)phenyloxy]propionate(+ Repr Cat 2, Repr Cat 3) Repr Cat 3)2,22,211-((3,3-((3,311,5,5,5,511-tetramethyl-(1,1-tetramethyl-(1,111-biphenyl)-4,4-biphenyl)-4,411-diyl)-bis(oxymethylene))-bis-oxirane-diyl)-bis(oxymethylene))-bis-oxiranethiophanate-methylthiophanate-methylm- and p-tolyloxy methyl oxiranem- and p-tolyloxy methyl oxiranetrifluoroiodomethanetrifluoroiodomethanetrisodium bis (7-acetamido-2-(4-nitro-2-oxidophenylazo)-3-sulphonato-1-naphthalato) chromatetrisodium bis (7-acetamido-2-(4-nitro-2-oxidophenylazo)-3-sulphonato-1-naphthalato) chromate

(ii)(ii)

APPENDIX 5 (Continued)APPENDIX 5 (Continued)

vanadium pentoxide (+ Repr Cat 3)vanadium pentoxide (+ Repr Cat 3)9-vinylcarbazole9-vinylcarbazole

APPENDIX 6APPENDIX 6 SUBSTANCES TOXIC TO REPRODUCTIONSUBSTANCES TOXIC TO REPRODUCTION

Category 1: Substances known to impair fertility in humans.Category 1: Substances known to impair fertility in humans. Substances known to cause developmental toxicity in humans.Substances known to cause developmental toxicity in humans.

R60R60 May impair fertility and may cause harm to the unborn child.May impair fertility and may cause harm to the unborn child.

2-bromopropane2-bromopropanetri lead bis (orthophosphate) (+ Repr Cat 3)tri lead bis (orthophosphate) (+ Repr Cat 3)

R61R61 May cause harm to the unborn child.May cause harm to the unborn child.

carbon monoxidecarbon monoxide4-hydroxy-3-(3-oxo-1-phenylbutyl)-2-benzopyrone4-hydroxy-3-(3-oxo-1-phenylbutyl)-2-benzopyronelead alkyls (+ Repr Cat 3)lead alkyls (+ Repr Cat 3)lead azide (+ Repr Cat 3)lead azide (+ Repr Cat 3)lead di (acetate) (+ Repr Cat 3)lead di (acetate) (+ Repr Cat 3)lead hexafluorosilicate (+ Repr Cat 3)lead hexafluorosilicate (+ Repr Cat 3)lead methanesulphonatelead methanesulphonatelead styphnate (+ Repr Cat 3)lead styphnate (+ Repr Cat 3)lead 2,4,6-trinitroresorcinoxide (+ Repr Cat 3)lead 2,4,6-trinitroresorcinoxide (+ Repr Cat 3)WarfarinWarfarin

Category 2: Substances which should be regarded as if they impair fertility in humans.Category 2: Substances which should be regarded as if they impair fertility in humans. Substances which are regarded as if they cause developmental toxicity. Substances which are regarded as if they cause developmental toxicity.

R60R60 May impair fertility and may cause harm to the unborn child.May impair fertility and may cause harm to the unborn child.

2,2-bis(42,2-bis(411-hydroxyphenyl)-4-methylpentane-hydroxyphenyl)-4-methylpentanebis (2-methoxyethyl) etherbis (2-methoxyethyl) etherdi –(2-ethylhexyl) phthalatedi –(2-ethylhexyl) phthalatedi-n-pentylphthalatedi-n-pentylphthalate3-ethyl-2-methyl-2-(3-methybutyl)-1,3-oxazolidine3-ethyl-2-methyl-2-(3-methybutyl)-1,3-oxazolidine2-ethoxyethanol2-ethoxyethanolmethoxyacetic acidmethoxyacetic acid2-methoxyethanol2-methoxyethanol2-ethoxyethyl acetate2-ethoxyethyl acetatefluazifop-butyl(ISO)fluazifop-butyl(ISO)formamideformamide2-methoxyethyl acetate2-methoxyethyl acetateN-methylacetamideN-methylacetamiden-pentyl-isopentyl phthalaten-pentyl-isopentyl phthalaten-propyl bromide (+ Repr Cat 3)n-propyl bromide (+ Repr Cat 3)

R61R61 May cause harm to the unborn child.May cause harm to the unborn child.

azafenden (+ Repr Cat 3)azafenden (+ Repr Cat 3)benzene butyl phthalate (+ Repr Cat 3)benzene butyl phthalate (+ Repr Cat 3)1,2-benzenedicarboxyli acids and dipentyl esters1,2-benzenedicarboxyli acids and dipentyl estersbinapacrylbinapacrylbis (2-methoxyethyl) phthalate (+ Repr Cat 3)bis (2-methoxyethyl) phthalate (+ Repr Cat 3)dibutyl phthalate (+ Repr Cat 3)dibutyl phthalate (+ Repr Cat 3)N,N-dimethylacetamideN,N-dimethylacetamidedimethylformamidedimethylformamidedinocapdinocapdinoseb, and its salts and esters (+ Repr Cat 3)dinoseb, and its salts and esters (+ Repr Cat 3)dinoterb, and its salts and estersdinoterb, and its salts and estersdiphenyl ether, octabromo derivativediphenyl ether, octabromo derivative2-ethylhexyl 3,5-bis(1,1-dimethyl)-4-hydroxyphenyl methylthioacetate2-ethylhexyl 3,5-bis(1,1-dimethyl)-4-hydroxyphenyl methylthioacetateethylene thioureaethylene thiourea

(ii)(ii)APPENDIX 6 (continued)APPENDIX 6 (continued)

etacelasiletacelasilflumioxazinflumioxazin2-[2-hydroxy-3-(2-chlorophenyl) carbamoyl-1-naphthylazo]-7-[2-hydroxy-3-(3-chlorophenyl)carbamoyl-2-[2-hydroxy-3-(2-chlorophenyl) carbamoyl-1-naphthylazo]-7-[2-hydroxy-3-(3-chlorophenyl)carbamoyl-1-1-

naphthylazo] fluorene-9-onenaphthylazo] fluorene-9-one2-methoxypropanol2-methoxypropanol2-methoxypropyl acetate2-methoxypropyl acetateN-methylformamideN-methylformamidetetrahydrothiopyran-3-carboxaldehydetetrahydrothiopyran-3-carboxaldehydetridemporphtridemporphtriethylene glycol dimethyl ethertriethylene glycol dimethyl ether

Category 3: Substances which cause concern for human fertility.Category 3: Substances which cause concern for human fertility. Substances which cause concern for humans owing to possible developmental Substances which cause concern for humans owing to possible developmental toxic effects. toxic effects.

R62R62 Possible risk of impaired fertility.Possible risk of impaired fertility.

N-[2-(3 acetyl-5-nitrothiophen-2-ylazo)-5-diethylaminophenol] acetamideN-[2-(3 acetyl-5-nitrothiophen-2-ylazo)-5-diethylaminophenol] acetamidebenzyl 2,4-dibromobutanoatebenzyl 2,4-dibromobutanoatebis(eta 5-cyclopentadienyl)-bis(2,6-difluoro-3[pyrrol-1-yl]-phenyl)titaniumbis(eta 5-cyclopentadienyl)-bis(2,6-difluoro-3[pyrrol-1-yl]-phenyl)titaniumbisphenol Abisphenol AR-5-bromo-3-(1-methyl-2-pyrrolidmylmethyl)-1H-indoleR-5-bromo-3-(1-methyl-2-pyrrolidmylmethyl)-1H-indole2-(4-2-(4-ttbutylphenyl) ethanolbutylphenyl) ethanolbutylmethyl ketonebutylmethyl ketone2-(4-tert-butylphenyl) ethanol2-(4-tert-butylphenyl) ethanolchinomethionatchinomethionat2-chloroacetamide2-chloroacetamidechloro 1,3-dihydro-2H-indol-2-onechloro 1,3-dihydro-2H-indol-2-onechlorotoluranchlorotoluran1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acidN,NN,N11-dihexadecyl-N,N-dihexadecyl-N,N11-bis(2-hydroxylethyl) propanediamide-bis(2-hydroxylethyl) propanediamide(S)-2,3-dihydro-1H-indole-2-carboxylic acid(S)-2,3-dihydro-1H-indole-2-carboxylic acid1,3-diphenylguanidine1,3-diphenylguanidine(ethylmethylsilylene) di [(4-methylpentan-2-one)oxime](ethylmethylsilylene) di [(4-methylpentan-2-one)oxime]n-hexanen-hexanehexan-2-onehexan-2-one2-(2-hydroxy-3,5-dinitroanilino) ethanol2-(2-hydroxy-3,5-dinitroanilino) ethanolnonylphenolnonylphenoloctamethylcyclotetrasiloxaneoctamethylcyclotetrasiloxane(R) –a-phenylethylammonium(-)-(1R,2S)-(1,2-epoxypropyl) phosphonate monohydrate(R) –a-phenylethylammonium(-)-(1R,2S)-(1,2-epoxypropyl) phosphonate monohydrate5,6,12,13-tetrachloroanthra (2,1,9-def: 6,5,10-d5,6,12,13-tetrachloroanthra (2,1,9-def: 6,5,10-d11ee11ff11) diisoquinoline-1,3,8,10(2H,9H)-tetrone) diisoquinoline-1,3,8,10(2H,9H)-tetronetrans-4-cyclohexyl-L-proline monohydrochloridetrans-4-cyclohexyl-L-proline monohydrochloridetrans-4-phenyl-L-prolinetrans-4-phenyl-L-prolinevalinamidevalinamide

R63R63 Possible risk of harm to the unborn child.Possible risk of harm to the unborn child.

amitroleamitrolebromoxynil and its octanoatebromoxynil and its octanoate1-(4-chlorophenyl)-4,4-dimethyl-3-(1,2,4-triazol-1-ylmethyl) pentan-3-ol1-(4-chlorophenyl)-4,4-dimethyl-3-(1,2,4-triazol-1-ylmethyl) pentan-3-olcyproconazolecyproconazolediethylene glycol monomethyl etherdiethylene glycol monomethyl ether2-ethylhexanoic acid2-ethylhexanoic acid

(iii)(iii)APPENDIX 6 (continued)APPENDIX 6 (continued)

fenpropimorphfenpropimorphfluazifop-P-butyl(ISO)fluazifop-P-butyl(ISO)ioxynil and its octanoateioxynil and its octanoateisoxaflutoleisoxaflutolemalachite green and its oxalatemalachite green and its oxalatemethylisocyanatemethylisocyanatemyclobutanilmyclobutaniloxadiargyloxadiargylpropylenethioureapropylenethioureatoluenetoluene1,2,4-triazole1,2,4-triazole1,2,5-trioxan1,2,5-trioxan

R62 and R63 R62 and R63 (as above)(as above)

carbon disulphidecarbon disulphidefenarimolfenarimol5-(3-butyryl-2,4,6-trimethylphenyl)-2-[1-(ethoxyimino) propyl]-3-hydroxycyclohex-2-en-1-one5-(3-butyryl-2,4,6-trimethylphenyl)-2-[1-(ethoxyimino) propyl]-3-hydroxycyclohex-2-en-1-one

APPENDIX 7APPENDIX 7 IARC CLASSIFIED CARCINOGENS*IARC CLASSIFIED CARCINOGENS*

Group 1: Carcinogenic to humans. Groups 2A: Probably carcinogenic to humans.Group 1: Carcinogenic to humans. Groups 2A: Probably carcinogenic to humans.

adriamycinadriamycinaristolochic acidaristolochic acidazacitidineazacitidineazathioprineazathioprinebischloroethyl nitrosoureabischloroethyl nitrosoureachlorambucilchlorambucilchloramphenicolchloramphenicolchlornaphazinechlornaphazine1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)chlorozotocinchlorozotocincisplatincisplatincyclophosphamidecyclophosphamidecyclosporincyclosporindibenzo[a,l] pyrenedibenzo[a,l] pyreneN-ethyl-N-nitrosoureaN-ethyl-N-nitrosoureaetoposideetoposidegallium arsenidegallium arsenideglycidolglycidolindium phosphideindium phosphideIQ(2-amino-3-methylimidazo[4,5-f]quinolineIQ(2-amino-3-methylimidazo[4,5-f]quinolinemelphalanmelphalanmethoxypsoralenmethoxypsoralenmethoxysalenmethoxysalenmethyl-CCNUmethyl-CCNUmethyl methanesulphonatemethyl methanesulphonateN-methyl-N-nitrosoureaN-methyl-N-nitrosoureamustard gasmustard gasmyleranmylerannitrogen mustardnitrogen mustardN-nitrosodiethylamineN-nitrosodiethylaminephenacetinphenacetinprocarbazine hydrochlorideprocarbazine hydrochloridetamoxifentamoxifenteniposideteniposidetetrachloroethylenetetrachloroethylenethiopetathiopetatreosulphantreosulphantris(2,3-dibromopropyl)phosphatetris(2,3-dibromopropyl)phosphatevinyl fluoridevinyl fluoride

Group 2B: Possibly carcinogenic to humans.Group 2B: Possibly carcinogenic to humans.

A-A-αα-C(2-amino-9H-pyrido[2,3-b]indole-C(2-amino-9H-pyrido[2,3-b]indoleAF-2AF-2amino-α-carbolineamino-α-carboline2-amino-5-(5-nitro-2-furyl)-1,3,4-thiadiazole2-amino-5-(5-nitro-2-furyl)-1,3,4-thiadiazoleamsacrineamsacrineo-anisidineo-anisidineantimony trioxideantimony trioxidearamitearamiteazaserineazaserinebenzofuranbenzofuranbenzo[c]phenanthrenebenzo[c]phenanthrene2,2-bis(bromoethyl)propane-1,3-diol2,2-bis(bromoethyl)propane-1,3-diol

*International Agency for Research on Cancer. Only substances not previously listed are included.*International Agency for Research on Cancer. Only substances not previously listed are included.

(ii)(ii)APPENDIX 7 (continued)APPENDIX 7 (continued)

bleomycinsbleomycinsbromodichloromethanebromodichloromethanebutylated hydroxyanisolebutylated hydroxyanisoleβ-butyrolactoneβ-butyrolactonecaffeic acidcaffeic acidcarbon blackcarbon blackcatecholcatecholchlorendic acidchlorendic acid3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone1-chloro-2-methylpropene1-chloro-2-methylpropenechlorophenoxy herbicideschlorophenoxy herbicides4-chloro-o-phenylenediamine4-chloro-o-phenylenediaminechloroprenechloroprenechlorothalonilchlorothalonilCI Acid Red 114CI Acid Red 114CI Direct Blue 15CI Direct Blue 15Citrus Red No 2Citrus Red No 2cobalt and its compoundscobalt and its compoundsp-cresidinep-cresidinedacarbazinedacarbazinedantrondantrondaunomycindaunomycinNN’-diacetylbenzidineNN’-diacetylbenzidine2,4-diaminoanisole2,4-diaminoanisole4,4’-diaminodiphenyl ether4,4’-diaminodiphenyl etherdibenz [a,h] acridinedibenz [a,h] acridinedibenz [a,j] acridinedibenz [a,j] acridine7H-dibenzo [c,g] carbazole7H-dibenzo [c,g] carbazoledibenzo [a,e] pyrenedibenzo [a,e] pyrenedibenzo [a,h] pyrenedibenzo [a,h] pyrenedibenzo [a,i] pyrenedibenzo [a,i] pyrenedichloroacetic aciddichloroacetic acid1,2-dichloroethane1,2-dichloroethane2,3-dibromopropan-1-ol2,3-dibromopropan-1-olp-dichlorobenzenep-dichlorobenzene3,3’-dichloro-4,4’-diaminodiphenyl ether3,3’-dichloro-4,4’-diaminodiphenyl ether1,3-dichloropropene1,3-dichloropropeneDichlorvosDichlorvosdiepoxybutanediepoxybutane1,2-diethylhydrazine1,2-diethylhydrazinediglycidyl resorcinol etherdiglycidyl resorcinol etherdihydrosafroledihydrosafrolediisopropyl sulphatediisopropyl sulphate4-dimethylaminoazobenzene4-dimethylaminoazobenzenetrans-2-[(dimethylamino) methylimino]-5-[2-(5-nitro-2-furyl)-vinyl]-1,3,4-oxadiazoletrans-2-[(dimethylamino) methylimino]-5-[2-(5-nitro-2-furyl)-vinyl]-1,3,4-oxadiazole3,7-dinitrofluoranthene3,7-dinitrofluoranthene3,9-dinitrofluoranthene3,9-dinitrofluoranthene1,6-dinitropyrene1,6-dinitropyrene1,8-dinitropyrene1,8-dinitropyreneethyl acrylateethyl acrylateethylbenzeneethylbenzeneethyl methanesulphonateethyl methanesulphonate2-(2-formylhydrazino)-4-(5-nitro-2-furyl)thiazole2-(2-formylhydrazino)-4-(5-nitro-2-furyl)thiazolefumonisin B1fumonisin B1furothiazolefurothiazoleGlu-P-1Glu-P-1

(iii)(iii)APPENDIX 7 (continued)APPENDIX 7 (continued)

Glu-P-2Glu-P-2glycidaldehydeglycidaldehydegriseofulvingriseofulvinHC Blue No 1HC Blue No 1hexachloroethanehexachloroethane1-hydroxyanthraquinone1-hydroxyanthraquinoneindeno[1,2,3-cd]pyreneindeno[1,2,3-cd]pyreneiron-dextran complexiron-dextran complexisopreneisoprenelasiocarpinelasiocarpineMeA-α-CMeA-α-Cmedroxyprogesterone acetatemedroxyprogesterone acetateMeIQMeIQMeIQxMeIQx5-methylchrysene5-methylchrysenemethy mercury cpdsmethy mercury cpds2-methyl-1-nitroanthraquinone2-methyl-1-nitroanthraquinoneN-methyl-N-nitrosourethaneN-methyl-N-nitrosourethanemethylthiouracilmethylthiouracilmetronidazolemetronidazolemitomycin Cmitomycin Cmitoxantronemitoxantronemonocrotalinemonocrotaline5-(morpholinomethyl)-3-[(5-nitrofurfurylidene)amino]-2-oxazolidinone5-(morpholinomethyl)-3-[(5-nitrofurfurylidene)amino]-2-oxazolidinonenafenopinnafenopinnaphthalenenaphthalenenifuradenenifuradeneniridazoleniridazolenitrilotriacetic acidnitrilotriacetic acid6-nitrochyrsene6-nitrochyrsene2-nitrofluorene2-nitrofluorene1-[C5-nitrofurfurylidene)]-2-imidazolidinone1-[C5-nitrofurfurylidene)]-2-imidazolidinoneN-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamideN-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamidenitromethanenitromethanenitrogen mustard N-oxidenitrogen mustard N-oxide1-nitropyrene1-nitropyrene4-nitropyrene4-nitropyreneN-nitrosodi-n-butylamineN-nitrosodi-n-butylamine3-(N-nitrosomethylamino) propionitrile3-(N-nitrosomethylamino) propionitrile4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanoneN-nitrosomethylethylamineN-nitrosomethylethylamineN-nitrosomethylvinylamineN-nitrosomethylvinylamineN-nitrosomorpholineN-nitrosomorpholineN’-nitrosonornicotineN’-nitrosonornicotineN-nitrosopiperidineN-nitrosopiperidineN-nitrosopyrrolidoneN-nitrosopyrrolidoneN-nitrososarcosineN-nitrososarcosineochratoxin Aochratoxin Aoil orange SSoil orange SSoxazepamoxazepampalygorskitepalygorskitepanfuran Spanfuran Sphenazopyridine hydrochloridephenazopyridine hydrochloridephenobarbitalphenobarbitalphenolphthaleinphenolphthaleinphenoxybenzamine hydrochloridephenoxybenzamine hydrochloride

(iv)(iv)APPENDIX 7 (continued)APPENDIX 7 (continued)

phenyl glycidyl etherphenyl glycidyl etherphenytoinphenytoinPhIPPhIPpolychloropenols and their sodium saltspolychloropenols and their sodium saltsPonceau MXPonceau MXPonceau 3RPonceau 3Rprogestinsprogestinspropylthiouracilpropylthiouracilriddellineriddellinesodium-o-phenylphenatesodium-o-phenylphenatesterigmatocystinsterigmatocystinstreptozotocinstreptozotocinstyrenestyrenetetrafluoroethylenetetrafluoroethylenetetranitromethanetetranitromethane4,4’-thiodianiline4,4’-thiodianilinethiouracilthiouraciltitanium dioxidetitanium dioxideTDITDItrichlormethinetrichlormethineTrp-P-1Trp-P-1Trp-P-2Trp-P-2Trypan blueTrypan blueuracil mustarduracil mustardvanadium pentoxidevanadium pentoxidevinyl acetatevinyl acetate4-vinylcyclohexene4-vinylcyclohexene4-vinylcyclohexene diepoxide4-vinylcyclohexene diepoxidezalcitabinezalcitabinezidovudinezidovudine

APPENDIX 8APPENDIX 8

Toxicity Data: Sources of InformationToxicity Data: Sources of Information

Databases:Databases:

Registry of Toxic Effects of Chemical Substances (NIOSH)Registry of Toxic Effects of Chemical Substances (NIOSH)Chemical Safety Newsbase (RSC)Chemical Safety Newsbase (RSC)Occupational Safety and Health (NIOSH)Occupational Safety and Health (NIOSH)Toxline (National Library of Medicine)Toxline (National Library of Medicine)Medline (National Library of Medicine)Medline (National Library of Medicine)Sigma-Aldrich-Fluka, Material Safety Data Sheets on CD-RomSigma-Aldrich-Fluka, Material Safety Data Sheets on CD-Rom

Bibliography:Bibliography:

Sigma-Aldrich Library of Chemical Safety Data, Vols I and IISigma-Aldrich Library of Chemical Safety Data, Vols I and IIHandbook of Identified Carcinogens and Noncarcinogens, vols I and II, Soderman,Handbook of Identified Carcinogens and Noncarcinogens, vols I and II, Soderman, CRC Press CRC PressDangerous Properties of Industrial Materials, Vols I, II and III, Von Nostrand, ReinholdDangerous Properties of Industrial Materials, Vols I, II and III, Von Nostrand, ReinholdThe Merck Index, Merck and Co IncThe Merck Index, Merck and Co IncRegistry of Toxic Effects of Chemical Substances, Vols I and II, NIOSHRegistry of Toxic Effects of Chemical Substances, Vols I and II, NIOSHDictionary of Substances and their Effects (DOSE) Vols 1-7, Richardson and Gargoli, RSCDictionary of Substances and their Effects (DOSE) Vols 1-7, Richardson and Gargoli, RSCBiochem Coc, Special Publication No 5 “Safety in Biological Laboratories”Biochem Coc, Special Publication No 5 “Safety in Biological Laboratories” D B Cater and E Hartree, 1977 D B Cater and E Hartree, 1977