Commission Regulation (EC) No 429/2008Show full title

3.3. Studies concerning the safety of use of the additive for users/workers

Workers can be exposed mainly by inhalation or topical exposure while manufacturing or handling or using the additive. For example, farm workers are potentially exposed when handling or mixing the additive. Additional information on how the substances are handled shall be provided.

An assessment of risk to workers shall be included. Where available, experience in the manufacturing plant is often an important source of information in evaluating the risks to workers from exposure to the additive itself by both airborne and topical routes. Of particular concern are additives/additive-treated feeds and/or animal excreta, which are in, or may give rise to, a dry powdery form, and feed additives which may have allergenic potential.

3.3.1. Toxicological risk assessment for user/worker safety

Risks to workers shall be assessed in a series of studies using the additive in the form for which the application has been submitted. Acute inhalation toxicity studies shall be performed unless the product is unlikely to form a respirable dust or mist. Studies on skin irritancy must be performed, and if these give negative results, mucous membrane (e.g. eye) irritancy shall be assessed. Allergenic potential/skin sensitisation potential shall also be assessed. The toxicity data generated to meet consumer safety (see 3.2.2) shall be used to assess the potential systemic toxicity of the additive. All these shall be assessed, if necessary, by direct measurement and specific studies.

3.3.1.1. Effects on the respiratory system

Evidence shall be provided that airborne levels of dust or mist of the additive will not constitute a hazard to the health of users/workers. This evidence shall include, where necessary:

• inhalation tests in laboratory animals;

• published epidemiological data and/or the applicants own data on its work plant and/or irritancy; and

• respiratory system sensitisation tests.

Acute inhalation toxicity studies shall be performed if particles or droplets with a diameter of less than 50 μm constitute more than 1 % on a weight basis of the product.

Protocols for acute inhalation toxicity studies should be in line with OECD Guideline 403. If sub-chronic toxicity studies are considered necessary, they should follow OECD Guidelines 412 (Repeated Dose Inhalation Toxicity: 28-day or 14-day study) or 413 (Sub-chronic Inhalation Toxicity: 90-day study).

3.3.1.2. Effects on the eyes and skin

Where available, direct evidence of absence of irritancy and/or sensitisation shall be provided from known human situations. This shall be supplemented by findings from validated animal tests for skin and eye irritation, and for sensitisation potential using the appropriate additive. Allergic potential — skin sensitisation potential shall also be assessed. Protocols for these studies should be in line with OECD Guidelines 404 (Dermal Irritation/Corrosion), 405 (Eye Irritation/Corrosion), 406 (Skin Sensitisation), 429 (Skin Sensitisation — local lymph-node assay).

If corrosive properties are known, either from published data or specific in vitro tests, then further in vivo tests shall not be performed.

Dermal toxicity must be considered, if the additive is toxic by inhalation. Studies must be in line with OECD Guideline 402 (Acute Dermal Toxicity).

3.3.1.3. Systemic toxicity

The toxicity data generated to meet consumer safety and other requirements (including repeated dose toxicity, mutagenicity, carcinogenicity and reproductive testing and metabolic fate) shall be used to assess systemic toxicity.

3.3.1.4. Exposure assessment

Information shall be provided on how the use of the additive is likely to give rise to exposure by all routes (inhalation, through the skin or by ingestion). This information shall include a quantitative assessment, where available, such as typical airborne concentration, dermal contamination or ingestion. Where quantitative information is not available, sufficient information shall be given to enable an adequate assessment of exposure to be made.

3.3.2. Measures to control exposure

Using the information from the toxicology and exposure assessment, a conclusion shall be drawn about the risks to health of the users/workers (inhalation, irritancy, sensitisation and systemic toxicity). Precautionary measures may be proposed to reduce or eliminate exposure. However, use of personal protective devices shall only be regarded as a measure of last resort to protect against any residual risk once control measures are in place. It is preferable, for example, to consider reformulation of the product.