A

carcinogen

is a substance that may cause cancer or increase its incidence by inhalation, ingestion or skin absorption. Cancer is a disease characterized by uncontrolled growth and division of cells. These cells have the ability to invade the organ where they originate, to travel through the blood and lymph fluid to other organs and grow in them. More than 200 different types of diseases (malignant tumours) are included under the term cancer. The latency period of the disease, i.e. the time that elapses between exposure to a carcinogen and clinical detection of resulting cancer can extend for several years.

Mutagens

are substances and mixtures which, if inhaled, swallowed or absorbed through the skin, may induce heritable genetic damage or increase its incidence. Former

Dangerous Substances Directive

, known as DSD (67/548/EEC) and the new

Regulation 1272/2008

(commonly known as CLP) identify carcinogenic and mutagenic substances with the following risk phrases (R) and hazard statements (H):

There is not a safe environmental or occupational exposure dose to carcinogens. Due to the severity of harm from exposure to carcinogens and mutagens they should be regarded as substances of very high concern, and their elimination/substitution should be promoted as a precautionary measure, following the principles of preventive action according to

Directive 89/391/EEC

on the safety and health of workers at work. In addition,

Directive 2004/37/EC

on the protection of workers from the risks related to exposure to carcinogens at work, establishes the employers’ obligation to substitute carcinogens and mutagens by other non hazardous or less hazardous substances whenever it is technically feasible. This obligation applies only to chemicals that meet the criteria for classification as carcinogens or mutagens of categories 1A or 1B (according to CLP Regulation) or 1 or 2 (according to DSD). Substances that meet the classification criteria as 1 and 2A according to the International Agency for Research of Cancer (IARC), are also substances of particular concern, and should be substituted. If the substitution of the carcinogen or mutagen is not technically possible, the employer shall ensure then the prevention and reduction of workers’ exposure (Article 5, Directive 2004/37/EC) and shall include specific measures of personal hygiene and individual protection (Article 10, Directive 2004/37/EC), such as:

Occupational exposure limit values assigned to some carcinogens do not constitute a reference to guarantee health protection. Additionally, when pregnant or breastfeeding workers are in risk of exposure, the employer must:

1. Take the necessary measures to prevent exposure through the adaptation of working conditions of affected workers.
2. Transfer the affected workers to a workstation compatible with her condition whenever the adaptation of working conditions is not possible.
3. Subsidised job suspension due to risks during pregnancy or breast feeding when changes of the workplace are not technically feasible.

Many national authorities, international agencies and even professional associations have developed lists of carcinogens according to their own classification criteria, which often do not coincide.

It defines as a

carcinogen

: a substance or a mixture of substances which induce cancer or increase its incidence. Substances which have induced benign and malignant tumours in well performed experimental studies on animals are also considered to be presumed or suspected human carcinogens unless there is strong evidence that the mechanism of tumour formation is not relevant for humans.

Carcinogenic

substances are classified in three categories according to the following criteria (see Annex I, point 3.6.2.)

Regulation 1272/2008 (CLP) defines mutation as a permanent change in the amount or structure of the genetic material in a cell. The term ‘mutation’ applies both to heritable genetic changes that may be manifested at the phenotypic level and to the underlying DNA modifications when known (including specific base pair changes and chromosomal translocations). The term ‘mutagenic’ and ‘mutagen’ will be used for agents giving rise to an increased occurrence of mutations in populations of cells and/or organisms. For the purpose of classification for germ cell mutagenicity, substances are allocated to one of two categories:

1. Positive result(s) from in vivo heritable germ cell mutagenicity tests in mammals; or
2. Positive result(s) from in vivo somatic cell mutagenicity tests in mammals, in combination with some evidence that the substance has potential to cause mutations to germ cells. It is possible to derive this supporting evidence from mutagenicity/genotoxicity tests in germ cells in vivo, or by demonstrating the ability of the substance or its metabolite(s) to interact with the genetic material of germ cells; or
3. Positive results from tests showing mutagenic effects in the germ cells of humans, without demonstration of transmission to progeny; for example, an increase in the frequency of aneuploidy in sperm cells of exposed people.

Category 2Substances which cause concern for humans owing to the possibility that they may induce heritable mutations in the germ cells of humans The classification in Category 2 is based on: Positive evidence obtained from experiments in mammals and/or in some cases from in vitro experiments, obtained from:

1. Somatic cell mutagenicity tests in vivo, in mammals; or

1. Other in vivo somatic cell genotoxicity tests which are supported by positive results from in vitro mutagenicity assays.

Note: Substances which are positive in invitro mammalian mutagenicity assays, and which also show chemical structure activity relationship to known germ cell mutagens, shall be considered for classification as Category 2 mutagens. Warning H341 Suspected of causing genetic defects (state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard)

1. Former Directive 67/548/EEC relating to the classification, packaging and labelling of dangerous substances (DSD, in force until 1^st December of 2010, with the exemption of substances already in the market before the cited date, for these substances, there will be no obligation to re-label or repackage until 1^st December, 2012).

DSD defines as carcinogenic substances and mixtures: substances or preparations which, if they are inhaled or ingested or if they penetrate the skin, may induce cancer or increase its incidence; DSD classifies carcinogens in three categories according to the following criteria (see Annex VI, section 4.2.1.): Category 1Substances known to be carcinogenic to man. There is sufficient evidence to establish a causal association between human exposure to a substance and the development of cancer.T: Tóxic R45 May cause cancer R49 May cause cancer by inhalation Category 2Substances which should be regarded as if they are carcinogenic to man. There is sufficient evidence to provide a strong presumption that human exposure to a substance may result in the development of cancer, generally on the basis of: appropriate long-term animal studies, other relevant information. T: Tóxic R45 May cause cancer R49 May cause cancer by inhalation

Substances which cause concern for man owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment.

DSD classifies mutagens in three categories according to the following criteria (see Annex VI, section 4.2.2.):

Substances known to be mutagenic to man.

Substances which should be regarded as if they are mutagenic to man.

There is sufficient evidence to provide a strong presumption that human exposure to the substance may result in the development of heritable genetic damage, generally on the basis of:

1. appropriate animal studies,
2. other relevant information.

Substances which cause concern for man owing to possible mutagenic effects.

Annex I of DSD includes a list of carcinogen and mutagen substances classified according to the previous criteria.

1. International Agency for Research on Cancer (IARC)

The International Agency for Research on Cancer is part of the World Health Organization. It is the international reference organization for this topic and publishes and regularly updates a list of carcinogens and a list of activities that may cause cancer, according to the following criteria:

Others agencies that have developed lists of carcinogens are:

1. American Conference of Governmental Industrial Hygienists (ACGIH)

The American hygienists’ professional association is an international recognised organization whose threshold limit values (TLV) are used as a reference all over Europe.

1. Occupational Safety and Health Administration (OSHA)

Carcinogenic list of the U.S Occupational Safety and Health Administration.

1. National Toxicology Program (NTP)

The National Toxicology Program of the U.S. Department of Health and Human Services is mandated to produce a biennial Report on Carcinogens. It classifies carcinogens into two groups:

1. California Proposition 65 (CP65)

List of chemicals known by the California state to cause cancer.

1. Substances that cause breast cancer

These substances are included at the database

Environment and Breast Cancer: Science Review

developed by the US Silent Spring Institute. The Science Review database includes information on 216 chemicals that increase mammary gland tumours in animal studies conducted by the US National Toxicology Program (NTP) or included in the International Agency for Research on Cancer (IARC) Monographs, 11th Report on Carcinogens (11th ROC), Carcinogenic Potency Database (CPDB), or Chemical Carcinogenesis Research Information System (CCRIS) database.

For each chemical, the database Environment and Breast Cancer: Science Review includes:

1. carcinogenic potential

1. ability to cause gene mutations

1. exposure in the general population and for women at work

1. other characteristics of chemical use, sources, and regulation.

1. Council Directive 89/391/EEC, of 12 June 1989 on the introduction of measures to encourage improvements in the safety and health of workers at work.

1. Regulation 1272/2008 (CLP), on classification, labelling and packaging of substances and mixtures.

1. Council Directive 67/548/EEC, of 27 June 1967 on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances.

1. Council Directive 98/24/EC of 7 April 1998 on the protection of the health and safety of workers from the risks related to chemical agents at work.

1. Directive 2004/37/EC of 28 June 1990 on the protection of workers from the risks related to exposure to carcinogens at work

1. Council Directive 97/42/EC of 27 June 1997 amending for the first time Directive 90/394/EEC on the protection of workers from the risks related to exposure to carcinogens at work

1. Council Directive 1999/38/EC of 29 April 1999 amending for the 2nd time Directive 90/394/EEC on the protection of workers from the risks related to exposure to Carcinogens at work and extending it to Mutagens

1. Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006, concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)

1. Council Directive 92/85/EEC of 19 October 1992 concerning the implementation of measures to encourage improvements in the safety and health of pregnant workers, workers who have recently given birth and women who are breastfeeding (Tenth individual Directive within the meaning of Article 16(1) of Directive 89/391/EECT)

The sources consulted for the preparation of this list are:

July 2010