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Toxicological data requirements (1/2)
Within the context of REACH, toxicological information is required for the specific purposes of classification and labelling, determination of the Persistent, Bioaccumulative and Toxic (PBT) status, Chemical Safety Assessment (CSA) and Report (CSR) and determination of any need for risk management measures. The toxicological information that shall be submitted for registration and substance evaluation purposes is specified in REACH annexes VI to XI. For an overview, see information requirements for registration. The health effects to be considered by registrants are detailed below.
Health effects considered
Skin and eye irritation/corrosion and respiratory irritation
Irritation and corrosion are local effects, i.e. changes occur at the site of first contact of the substance with the skin, eye, or mucous epithelia such as the respiratory tract. Corrosive substances may destroy living tissues with which they come into contact after single exposure. Irritant substances are non-corrosive substances which, through immediate contact with the tissue under consideration may cause inflammation after single exposure. Substances that cause irritant effects only after repeated exposure are not classified as irritants. Skin and/or eye irritation refers to the production of fully reversible changes following application of a substance (in the case of eye irritation, when application is performed to the anterior surface of the eye). Corrosive substances produce irreversible effects such as necrosis through the epidermis and into the dermis, ocular tissue damages or decay of vision. Chemicals which are classified for respiratory irritation may provoke irritations similar to skin or eye irritations. They may also cause other toxic effects, in relation with interactions with the vegetative nervous system and leading to reflex responses (sneezing, coughing, respiratory symptoms, etc). These effects are reversible. Testing for respiratory irritation is not required under REACH as no validated guidelines are available. Nevertheless, existing and available data that provide evidence of the respiratory irritation potential of a substance should be taken into account.
Skin and respiratory sensitisation
A sensitiser is an agent that is able to cause an allergic response in susceptible individuals. The allergic reaction occurs if a previous exposure has led to the development of immunity against the substance (i.e. sensitisation step). The effects arise on the occasion of later contact: allergic contact dermatitis, allergic rhinitis, asthma.,etc. No information requirements are present under REACH for respiratory sensitisation. However, respiratory sensitisers are indicated for harmonised classification and labelling in article 36 of regulation (EC) no 1272/2008.
Acute toxicity concerns the adverse effects, which may result from a single exposure or multiple exposures within 24 hours to a substance. Exposure relates to the oral, dermal or inhalation routes. Assessment of the acute toxic potential of a chemical is necessary to determine the adverse health effects that might occur following accidental or deliberate short-term exposure: the types of toxic effects, their time of onset, duration and severity, the dose-response relationships, and the sex differences in response. The investigated damages can be clinical signs of toxicity, abnormal body weight changes, and/or pathological changes in organs and tissues, which in some cases may result in death.
Repeated dose toxicity
The repeated dose toxicity comprises the general toxicological effects occurring as a result of repeated daily exposure to a substance for a part of the expected lifespan (sub-acute or sub-chronic exposure) or for the major part of the lifespan (chronic exposure).
Reproductive toxicity is of obvious high concern because the continuance of the human species is dependent on the integrity of the reproductive cycle. It is characterised by multiple diverse endpoints, such as impairment of male and female reproductive functions or capacity (fertility), induction of non-heritable harmful effects on the progeny (developmental toxicity) and effects on or mediated via lactation.
Mutagenicity and carcinogenicity
Mutagenicity refers to the induction of permanent transmissible changes in the amount or structure of the genetic material of cells or organisms. These changes may involve a single gene or gene segment, a block of genes or chromosomes.
Chemicals are defined as carcinogenic if they induce tumours, increase tumour incidence and/or malignancy or shorten the time to tumour occurrence. Carcinogenic chemicals have conventionally been divided into two categories according to the presumed mode of action. Non-genotoxic modes of action include epigenetic changes, i.e., effects that do not involve alterations in DNA but that may influence gene expression, altered cell-cell communication, or other factors involved in the carcinogenic process. The objective of investigating the carcinogenicity of chemicals is to identify potential human carcinogens, their mode(s) of action, and their potency.
The expression of toxicity arising from exposure to a substance is a consequence of a chain of events that results in the affected tissues of an organism receiving the ultimate toxicant in amounts that cause an adverse effect. The concentration of the ultimate toxicant at the biological target site depends on the absorption, distribution, metabolism and excretion. According to REACH annexe VIII, the assessment of these processes, i.e. the toxicokinetics behaviour is required from the relevant available information. There is no obligation to generate new data.