These documents are issued by the shipping line, airline, international trucking company, railroad, freight forwarder or logistics company. To the shipping company and freight forwarder transport documents provide an accounting record of the transaction, instructions on where and how to ship the goods and a statement giving instructions for handling the shipment. The responsibility for the management and processing of shipping documents will depend on the sale conditions Incoterms agreed between de parties. We describe below the main transport documents explaining for each one: what are used for? CMR DOCUMENT The CMR transport document is an international consignment note used by drivers, operators and forwarders alike that govern the responsibilities and liabilities of the parties to a contract for the carriage of goods by road internationally.

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When it has more it is classified according to the evidence for each type of hazard, for example: CM: benzene is carc. However the current classification does not inlcude substances generated during work and natural substances; for workplace carcinogens see also the chapter on European legislation below. Hazards and mechanism of action Carcinogens and mutagens Carcinogenesis and mutagenesis processes and the relation between them are not completely understood but at present two mechanisms are considered: one inducing cancer by involving mutations caused by genotoxic substances and one that induces or promotes it by other means caused by non-genotoxic substances.

Genotoxic agents or their metabolites induce direct changes in the genetic material DNA while the non-genotoxic agents are considered to be involved in other types of mechanisms, for example acting as tumour promoters. Genotoxic and non-genotoxic substances may interact at the different stages of carcinogenicity. The body is normally programmed by encoded genetic information to control cell growth in order to insure development, functionality and repair of tissues.

A variety of factors including exposure to CMRs may disturb these mechanisms and transform normal cells into malignant ones. Malignant cells do not have the same functions, nor do they multiply or die as the cells from which they are derived.

They tend to proliferate fast and invade the neighbouring tissues or enter the bloodstream or lymphatic system and spread in distant parts of the body metastasis. This can lead to permanent changes: mutations. Numerous mutations occur in a lifetime. Many of them are neutral, but some can negatively affect the cells in which they occurred. When mutations occur in germ cells male or female reproductive cells the changes they cause are heritable.

Germ cell mutagenicity can act over several generations and cause problems like reduction of fertility, malformations, genetic diseases, embryonic death or genetically determined phenotypic alterations. Because of their mechanism of action germ cell mutagens are likely to have carcinogenic effects.

Mutations that occur in somatic cells non-reproductive cells can increase the likelihood of cancer, but somatic mutations are not passed along to the next generation. Non-genotoxic carcinogens are assumed to participate in the carcinogenesis process by a mechanism not related directly to the genetic material. They have been shown to act as tumour promoters, endocrine modifiers, immuno-suppressants or inducers of tissue-specific toxicity. An example of a non-genotoxic carcinogen is sulfuric acid mist IARC class 1 carcinogen.

At high concentrations it generates chronic irritation of the respiratory tract that results in reactive stimulation of growth and promotion of cancer. At lower exposure levels, which do not generate irritation, the carcinogen hazard has not been confirmed [5]. Some pesticides are also non-genotoxic carcinogens. There are differences in how each human individual responds to chemicals metabolic fingerprint.

Tissue specificity has also been noticed. Data show that certain CMRs can be associated to target organs organs that are most affected , like nasal cancer to exposure to chromium VI compounds, pleural mesothelioma to asbestos exposure, scrotal cancer from polycyclic aromatic hydrocarbons like benzo[a]pyrene from soot.

The mechanism of action is important when setting strategies for risk control. For genotoxic carcinogens a non-threshold approach is generally considered. Any exposure to a genotoxic carcinogen that reaches its biological target and reacts with it increases the probability of cancer and there is no safe range of exposure levels [6].

Exposure should be avoided or kept as low as possible. Non-genotoxic carcinogens may be treated as threshold toxicants. Reprotoxic substances Reproductive toxicity refers to direct and specific effects on sexual function and fertility.

This includes alterations to the reproductive system e. Effects transmissible via lactation to breastfed babies are also included. Health effects of reprotoxicants for pregnant women depend on when they are exposed. Exposure during the first three months of pregnancy might cause induction of metabolic disorders in the mother body, abnormal embryogenesis, birth defects or miscarriage. During the last six months, exposure could slow foetus growth, affect the development of its brain or cause premature labour.

Reprotoxics can affect e. There is some evidence of epigenetic effects or transgenerational effects of paternal exposure that can impact on the pregnancy outcome, e. These effects can be manifested at any point in the lifetime of the organism. The major manifestations of developmental toxicity include death of the developing organism, structural malformations, altered growth and functional deficiency.

In a survey carried out in France evaluated 50 potential reprotoxic substances scoring them for danger and exposure. The first ten substances according to this method were: di 2-ethylhexyl phthalate, benzyl butyl phthalate, dibutyl phthalate, cadmium, lead, hexachlorobenzene, toluene, nonylphenol, ethylene glycol ethyl ether, benomyl.

Alkylphenols and related chemicals have the effect of hormone mimicking imitating effects, and reduced male fertility, testicular size and sperm quality [9].

Endocrine disruptors Endocrine disruptors are chemicals that can act on the endocrine system to disturb its mechanisms or to initiate processes at abnormal times in the life cycle. Many of the endocrine disruptors affect reproductive functions are reprotoxicants , but some may influence other functions, like the thyroidal one, for example.

Phthalates and nonylphenols are examples of known endocrine disruptors affecting the reproductive functions. Hazard communication For substances or products classified as dangerous, the label is the most concise means of hazard communication.





Carcinogenic, mutagenic, reprotoxic (CMR) substances


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