Occupational exposure to biocides (disinfectants and metal working fluids) - OSHwiki (original) (raw)

Introduction

Biocides are intended to combat harmful and unwanted organisms. They have a wide range of use: from disinfection and preservation up to pest control. Biocides are divided into 22 product types (table 1) and are used in everyday life in households and at work (e.g. food industry, agriculture, healthcare). They can have toxic, carcinogen, endocrine disrupting properties, and may have adverse effects on human and the environment. Biocides are used by workers in many industries and sectors. The use of biocides in the workplace (i.e. if substitution or elimination is not possible) requires adequate protection, information, and training for workers.

What are biocides?

Biocides are chemical substances or microorganisms which can deter, render harmless, and kill living organisms. They are used to control and kill harmful and unwanted organisms such as mould, bacteria, algae, insects, and rodents. They are used in everyday life in households (cleaning and disinfection) as well as at workplaces (e.g. in the food industry, agriculture, healthcare, metal industry). Biocides are dangerous if not used correctly - not only for unwanted organisms, but also for users and other living organisms.

Biocides are defined in EU Regulation No 528/2012 article 3 (1a)[1] as: “any substance or mixture, in the form in which it is supplied to the user, consisting of, containing or generating one or more active substances, with the intention of destroying, deterring, rendering harmless, preventing the action of, or otherwise exerting a controlling effect on, any harmful organism by any means other than mere physical or mechanical action" and “any substance or mixture, generated from substances or mixtures which do not themselves fall under the first indent, to be used with the intention of destroying, deterring, rendering harmless, preventing the action of, or otherwise exerting a controlling effect on, any harmful organism by any means other than mere physical or mechanical action." It also states that “A treated article that has a primary biocidal function shall be considered a biocidal product." Products intended to protect plants (Plant Protection Products - PPP) are not called biocides but pesticides.

What are the main uses of biocides?

Biocidal products can contain one or more active substances, and may be of biological or chemical origin. They are applied as chemicals or microorganisms, mixtures, or incorporated in products. Biocides are mainly used in:

What are the health effects of biocides?

Biocides are designed to control harmful, unwanted organisms and microorganisms and these effects are not necessarily limited to the targeted harmful organisms. Humans may be affected when using the products or using treated materials during their lifetime, especially if they are not stored, applied or disposed of properly. Non-target organisms in the environment can also be affected when the substances enter the environment[2]. There are a variety of different biocide substance classes; at least 30% of biocides are endocrine disruptive, persistent, toxic to water organisms or carcinogenic, according to PAN - the Pesticide Action Network, a collation of 600 NGOs.[3] Formaldehyde, for instance, a highly effective, broad spectrum disinfectant, is a known skin sensitizer and is classified by IARC as a human carcinogen. Rossmore describes biocides as “a necessary evil to prevent microbiological disasters".[4]

Workers may be exposed to biocides either directly (primary exposure) or indirectly (secondary exposure) Primary exposure occurs if the worker/operator actively uses the biocidal product. Secondary exposure may occur after the actual use or application of biocidal products, e.g. when cleaning contaminated work clothes.[5]

In general, biocide exposure may occur by inhalation or dermal contact. Inhalation exposure occurs during spray application or when biocides evaporate from products and treated articles. Dermal exposure occurs when biocides or treated articles are used, cleaned, transported, or stored.

Biocides pose a particular risk to pregnant women, unborn life, small children, or people with serious chronic illness. Health hazards caused by disinfectants or other dangerous biocides include effects on skin, eyes, respiratory system, nervous system, and other organs.

The French centre of poison control and toxicovigilance analysed all incidents related to biocides from 1999 to 2009 in France. 5312 persons were harmed from biocides, mainly from exposure to biocide product type PT 2 (disinfectants and algaecides not intended for direct application to human or animals), PT4 (food and feed area disinfectants) and PT14 (rhodenticides) (table 1).[6] Data from the Belgian poison centre (2018 – 2020) show that only a small percentage of incidents are work-related (2,3% of biocides PT 1 Human hygiene and 6,6% of biocides PT 2 Disinfectants and algaecides). In 2020 the number of reported cases increased significantly in comparison with the previous years due to the COVID-19 pandemic and the widespread use of disinfectants[7].

The increasing use of biocides in human medicine, livestock farming, food treatment, personal care, and households has resulted in a significant release of biocidal substances into the environment, and may be associated with an increase in antibiotic resistance in bacterial pathogens.[8] Workers most at risk of antibiotic resistant bacteria are healthcare workers including laboratory workers and hospital staff, workers in the food industry such as butchers, slaughterers, farmers or poultry workers.[9] Researchers at the John Hopkins Bloomberg School of Public Health found that poultry workers in the US are 32 times more likely to carry E. coli bacteria resistant to the commonly used antibiotics, than others outside the poultry industry.[10]

Laboratory experiments have demonstrated that biocides may lead to an increased selective pressure towards disinfectant and antibiotic resistance. According to Randall et al. [11], Salmonella enterica, which is associated with foodborne Salmonellosis, was able to tolerate relatively high concentrations of disinfectants and to develop cross-resistance to certain antibiotics. Antibiotics used in animal production could leave residues in milk, meat or eggs, and could have negative effects on consumers. Consequently, Regulation 470/2009/EC [12]on maximum residue levels in food states that all antimicrobials must obtain pre-marketing approval.

EU legislation and authorisation

Biocides are used in a wide range of application areas, and although they are usually only added in comparatively low quantities to the final product, they represent global sales of approx. 12.7billionin2019,andisexpectedtoreach12.7 billion in 2019, and is expected to reach 12.7billionin2019,andisexpectedtoreach20.7 billion by 2027. The halogen-based biocide segment holds the largest market share, owing to increase in demand from oil & gas sector, chemical, pulp & paper, and other industries[13].

Pesticides and biocides must be proven safe to humans, animals, and the environment before going to market (import, use, sell, store, supply or advertise). The European Union has developed a comprehensive regulatory framework, laying down rules for the authorisation of pesticides and biocides, as well as for risk assessment and the authorisation procedure. The Biocide Regulation 528/2012 (BPR) only affects biocidal products and active substances.[1]

EU legislation for entry to the market

The introduction of EU-wide biocide legislation was necessary because authorisation procedures for biocidal products had only been established in some countries (e.g. Sweden, UK, The Netherlands), whilst most Member States did not require authorisation for many biocidal products.[14]

The aim of the Biocidal Products Directive (Directive 98/8/EC - BPD) was to harmonise the European market for biocidal products and their active substances and to ensure high standards of protection for humans, animals and the environment. The Directive established positive lists of approved active substances in Annexes I, IA and IB.[14] The BPD, adopted in 1998, was revised and replaced by the Biocidal Products Regulation (EU 528/2012 – BPR) in 2012. The BPR is applicable as of 1 September 2013.

The revision of the BPD was necessary as a number of weaknesses had been identified during the 11 years of implementation. It was updated and adapted to recent policy developments for managing problems with the authorisation and mutual recognition procedure.[1] The BPD had been criticised as being too complicated and too expensive, especially for SMEs. The industry wanted to have simpler and faster authorisation procedures.[15]

BPR and BPD have similarities, such as a two-step approach to authorisation: active substances are first tested and approved and included in a list (Annex I), with subsequent authorisation of a product containing the active substance.[1] However, there are several important changes, such as the range of products covered, data generation requirements, and the data compensation framework. Other changes include:

Compared to the old system, where applications for authorisation had to be made to individual Member States, companies now have two options to apply for permission to sell biocides or treated products: Union authorisation and the approval for an active substance at national level.

Withdrawal notices and “non-inclusion" decisions can be found on the website of ECHA, as well as the positive list of approved substances (Annex I, IA and IB)https://echa.europa.eu/regulations/biocidal-products-regulation/approval-of-active-substances/list-of-approved-active-substances. The lists of non-inclusion decisions contain active substances that must be removed from the EU market, including the date from which biocidal products containing these active substances should no longer be sold.

The BPD introduced the substitution principle and the promotion of low-risk substances[3] in article 1 (5 i). The BPR has further extended and emphasised this principle, e.g. in its preamble (paragraph 14 and 15): “Active substances should be designated as candidates for substitution if they have certain intrinsic hazardous properties. In order to allow for a regular examination of substances identified as candidates for substitution, the approval period for those substances should not, even in the case of renewal, exceed seven years." Candidates for substitution are identified during the approval of active substance stage, which is further reflected in the product authorisation stage, where candidates for substitution trigger a comparative assessment of biocidal products. Following the comparative assessment, an authorisation may not be granted or may be restricted if another biocidal product is available showing a significantly lower risk while being sufficiently effective[16].

Classification and labelling

Biocides are divided into four main groups and 22 product types (PT) (i.e. application categories).[17] A list of the types of biocidal products and their descriptions is set out in Annex V of the BPR (Table 1). The list demonstrates the wide range of biocides, including products which aren’t so obviously harmful, such as hygiene sprays.

Table 1: Main groups of biocides and product types

1. Disinfectants 2. Preservatives
PT 1: Human hygiene (products for the primary purpose of disinfecting the skin or scalp) PT 2: Disinfectants and algaecides not intended for direct application to human or animals PT 3: Veterinary hygiene disinfectants PT 4: Food and feed area disinfectants PT 5: Drinking water disinfectants PT 6: Preservatives for products during storage (In-can preservatives) PT 7: Film preservatives PT 8: Wood preservatives PT 9: Fibre, leather, rubber and polymerised materials preservatives PT 10: Construction material preservatives PT 11: Preservatives for liquid-cooling and processing systems PT 12: Slimicides PT 13: Metalworking or cutting fluid preservatives
3. Pest control 4. Other biocidal products
PT 14: Rodenticides PT 15: Avicides PT 16: Molluscicides, vermicides and products to other invertebrates PT 17: Piscicides PT 18: Insecticides, acaricides and products to control other arthropods PT 19: Repellents and attractants PT 20: Control of vertebrates PT 21: Antifouling products PT 22: Embalming and taxidermist fluids

Source: BPR [1]

Labelling and classification requires the evaluation of the intrinsic hazard of a substance. Current classification and labelling is regulated by Regulation EC No 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP)[18]. Before going to market, suppliers of biocides are obliged to ensure that their classification, labelling and packaging is in accordance with the Regulation on Classification, Labelling and Packaging of Substances and Mixtures (CLP - EC No. 1272/2008).[18] Classification, packaging and labelling of biocidal products must be done in accordance with the approved summary of biocidal product characteristics, in particular the hazard statements and the precautionary statements, as referenced in BPR (article 22(2)). The Biocidal Products Regulation defines detailed rules for classifying and labelling preparations, including pesticide and biocides for human health and environmental hazards. The label must be clearly visible, easily legible, appropriately durable and “shall not be misleading or give an exaggerated impression of the product and, in any case, not mention the indications 'low-risk biocidal product`, 'non-toxic`, 'harmless` or similar indications".[1]

Safety Data Sheets for active substances and biocidal products shall be prepared and made available in accordance with Article 31 of Regulation (EC) No 1907/2006 (REACH)[19], where applicable.[1] The supplier of a treated article must, on request, provide the consumer with information on the biocidal treatment of the treated article, within 45 days, free of charge. Every advertisement for a biocidal product has to be accompanied by the sentence “Use biocides safely: Always read the label and product information before use" (BPR, Article 72(1)).

Acceptable operator exposure levels

Biocides are used by workers in many industries. Workers handling dangerous substances are protected by the Framework Directive 89/391/EEC[20] on the protection of workers safety and health with its daughter Directives 2004/37/EC[21] (carcinogens, mutagens and and reprotoxic substances) and 98/24/EC[22] (dangerous substances).

Member States are obliged to report on the implementation of the BPR which includes providing data on poisoning incidents. Most of the poisoning incidents are accidental and only a minority of the cases are due to occupational exposure. More detailed information on the occupational incidents is only available for Latvia where 24 cases of occupational exposures were registered between 2015 and 2017. They mostly involved disinfectants and the professionals concerned were generally healthcare professionals (e.g. nurses, anaesthesiologists)[23].

Manufactures of biocides have to supply information to facilitate risk assessment for the product, including information about the acute, short-term and chronic toxicity, as well as the operator exposure. For operators – i.e. workers involved in activities related to biocides, such as mixing, loading and transport, cleaning and maintenance tasks, the risks of using or coming into contact with biocides depend on:

The Acceptable Operator Exposure Level (AOEL) is a health-based limit value, and is defined as the maximum amount of active substances to which workers or operators may be exposed by all routes without any adverse effects. It is established on the basis of the full toxicological data (e.g. acute and chronic toxicity, CMR, neurotoxicity) and included in the assessment and review of pesticides and biocides within Europe.

Workers exposed to biocides

Workers who come into contact with dangerous substances as a consequence of their professional life are, in general, protected by the Framework Directive 89/391 EEC[20] and the daughter Directives related to dangerous substances (e.g. Chemical agents Directive 98/24/EC[22], Carcinogens, Mutagens and and Reprotoxic substances Directive 2004/37/EC[21] , Biological Agents at Work Directive 2004/37/EC[24]). People working with biocides may suffer from illnesses years later in life which were caused by incorrect management of biocide exposure. In order to reduce the risks, companies must ensure that they take full responsibility for minimising possible health problems.[25] The following chapters describe the use of biocides in two different occupations, covering two different substance groups: disinfectants and preservatives.

Biocides are heavily used in healthcare. They are used for surfaces, water, equipment, and antisepsis, and also to sterilise medical devices and for the preservation of pharmaceutical and medicinal products. Many healthcare products contain biocides, such as linen, curtains, mattresses, and mops. Healthcare workers come in contact with biocides in their daily work and may be at risk of adverse health effects.

Metalworking fluids (MWF) are used in all stages of metal processing and in large and small industries where metal working is done. They prevent parts from heating up, as well as corrosion and tool wear. Some MWFs contain biocides and may cause adverse health effects through skin contact and inhalation. A high number of workers in car manufacturing, farm equipment, aircraft, and heavy machinery are exposed to MWFs.[26]

Exposure to disinfectants in healthcare

Biocides are essential in preventing and controlling infections in the healthcare environment. Many disinfectants are non-specific and act against a broad spectrum of microorganisms. Biocides used in healthcare belong to product type PT 2 (table 1), which includes the most wide-ranging application areas, with about 165 substances. The annual consumption of PT2 substances represents 50% of total tonnage of all active substances in the EU.[27]

In terms of the production tonnage, the most important chemicals in PT 2 are chlorine, ethylene oxide, hydrogen peroxide, sodium hypochlorite, symclosene and troclosene sodium.[27]

Cleaning, crucial for preventing infections in healthcare, has a dual function: a) surface cleanliness and b) infection prevention and control. This requires intensive and frequent cleaning with a wide range of products, including disinfectants.[28] Waiting areas often need cleaning without disinfectants; patient rooms need cleaning with low level disinfection, operating theatres and the intensive care unit require high-hygienic standard disinfection, and the same applies to medical instruments.

Disinfection in the healthcare sector is carried out using different application methods. Typical methods include cleaning with a cloth, disinfectant towels or paper to distribute the disinfectant, and using sprays, or disinfection baths for instruments. Cleaning and disinfection work in the healthcare is done by different occupational groups. Medical doctors and nurses perform minor cleaning and disinfecting work, such as disinfection of hands and skin, as well as surface and instrument disinfection. Cleaning workers perform routine cleaning tasks throughout the day, such as surface disinfection, cleaning sanitary facilities and disinfecting beds.[29]

Prevention measures

All chemical disinfectants are, by their nature, potentially harmful or toxic to living organisms. Commonly used cleaners, disinfectants, and sterilising agents in healthcare facilities may directly or indirectly harm workers. Formaldehyde has a broad spectrum of activity and is highly effective, but it is a substance of high concern because it is classified as carcinogen by IARC and a known skin sensitizer. Glutaraldehyde, a widely used disinfectant, is a strong irritant to the skin, eyes, and respiratory system.

Employers are legally obliged to carry out a risk assessment, according to the Framework Directive 89/391 and its daughter Directives, and related National OSH legislation. The employer must ensure that the risk to workers’ health and safety from dangerous substances is eliminated or reduced to a minimum. In order to fulfil this obligation, the first priority for the employer is to substitute or eliminate the risk of biocides - the first step in the hierarchy of risk control. This can be done by using alternative disinfectants or replacing them with less harmful procedures, substances, preparations or products. Questions to be considered[30]:

Various databases support companies when they want to substitute hazardous substances:

If substitution is not possible, engineering control measures are the next level in the hierarchy. They help to prevent worker contact with biocides, or reduce it to a lower level, e.g. through the use of closed automatic cleaning systems, sterilisation machines, or technical ventilation systems.

The third level in the hierarchy are work-practice and administrative control measures. Employers should develop and implement a comprehensive safety and health programme as part of their management, which should include[31]:

The last priority in the hierarchy is the use of individual protective measures, including protective gloves, overalls, goggles or respiratory masks. The use of personal protective equipment is necessary when a danger for workers remains, after taking the necessary technical or organisational measures.[29]

Only a full understanding of the properties of biocides and the appropriate precautionary and protective measures will ensure safety and efficiency at work. Employers must ensure such measures are in place, and offer related occupational safety training.

Various guidelines provide help and instructions for working safely with disinfections, e.g.:

Exposure to Metalworking-fluid preservatives

Metalworking fluids (MWFs) are used in different sectors of the metal industry: In the metal forming, metal cutting and galvanic industry. The main functions of MWFs are: cooling, lubricating, flushing away chips and swarf from the cutting zone, and reducing the friction between tool and metal parts. Operations such as grinding, cutting, and drilling of metal parts generate a huge amount of heat and need to be cooled. In addition, MWFs provide corrosion protection for machines and tools.[26] They are necessary to ensure productivity, quality, and to prolong the lifetime of tools and machines. Table 2 gives examples of workers exposed to MWFs.

MWFs may be complex mixtures of oils, detergents, surfactants, biocides, lubricants, anti-corrosive agents, and other potentially toxic ingredients. Four different types of MWFs[31] exist:

Water-based fluids and fluids based on vegetable oils can be contaminated with bacteria and fungi. MWF preservatives (e.g. bactericides or fungicides) are added to the fluids to control microbial growth and deterioration. This is necessary to maintain the quality of the fluids and to protect workers from exposure to biological agents and endotoxins, causing machine operator’s lung (MOL), hypersensitivity pneumonitis or Legionnaire’s disease. MOL has been related to microorganisms growing in MWFs, especially Mycobacterium immunogenum.[32]Legionella pneumophila has been occasionally isolated from dilute metalworking fluids. These contaminated fluids have been associated with sporadic incidences of these diseases in workshop environments.[33] But according to new researches the risk of Legionella infection of MWF is extremely low.[34] MWFs based on pure mineral oils or solvent based fluids do not generally contain biocides.[35] The biocides on the market are ready-to-use MWF mixtures treated with active substance, or biocides (concentrate) intended for the direct treatment of large machine MWF systems. The ready-to-use MWF already treated with biocides are mainly used in small systems[36].

Formaldehyde and formaldehyde-releasing substances are very cost-effective biocides, and have been used for many years in metalworking fluids. The most common formaldehyde-donor is triazine, also known as hexahydrotriazine. However, as previously mentioned, formaldehyde is classified by IARC as a carcinogen. A binding occupational exposure limit for formaldehyde has been added to annex III of Directive 2004/37/EC Carcinogens, mutagens or reprotoxic substances at work (amending Directive 2019/983/EU)[21]. In 2020, following an evaluation by the German Government, formaldehyde was approved as a biocidal active substance for PT 2 and 3 for a reduced period of 3 years. Companies placing disinfectant biocidal products containing formaldehyde on the market, needed to apply for a marketing authorisation before 1 February 2022, with supporting arguments demonstrating that the products do not cause human or environmental exposure and why they are essential[37][38]. Formaldehyde is not approved as a biocide active substance PT 13 Metalworking or cutting fluid preservatives. The list of approved substances can be found on the ECHA website https://echa.europa.eu/information-on-chemicals/biocidal-active-substances?p_p_id=dissactivesubstances_WAR_dissactivesubstancesportlet&p_p_lifecycle=1&p_p_state=normal&p_p_mode=view&_dissactivesubstances_WAR_dissactivesubstancesportlet_javax.portlet.action=dissActiveSubstancesAction.

Exposure to MWF preservatives during machining operations can occur through inhalation and skin contact. Skin contact, which can cause irritation, may occur when workers dip their hands into the fluid, flood the machine/tool, or handle parts and tools covered with fluid. Inhalation exposures occur from breathing MWF mist or aerosol, and can cause occupational asthma, bronchitis, irritation of the upper respiratory tract, and other breathing difficulties, such as the machine operator’s lung (see above) or hypersensitivity pneumonitis (HP).[32]

Table 2: Workers exposed to MWF preservatives

Exposed workers
Engineering machinists
Machinery mechanics
Metalworkers
Machine operators and setters
Workers assembling components
Workers handling components

Source: Whittaker, 1997 [39]

Prevention measures

The hierarchy of control measures to prevent or reduce worker exposure to dangerous substances - European Directives 89/391[20] and 2000/54/EC[1] - indicates that the first priority and most effective control level is the elimination or substitution of hazardous substances with safe, less irritating or non-allergenic additives or MWF constituents.

Where risks to workers cannot be prevented by elimination or substitution, engineering controls should be next considered. Engineering controls are physical changes to the work area/process that effectively remove or reduce the risks to workers' health, such as process modification and isolation to limit the dispersal of MWFs (closed systems) or removing the hazard through effective ventilation. Large industries use MWFs in closed systems, but workers may be exposed during maintenance work.

The next step in the hierarchy are work-practice and administrative controls to assure proper MWF maintenance and workplace cleanliness. Employers should develop and implement a comprehensive safety and health programme as part of their management, including safety and health training, and a skin protection plan. NIOSH[31] recommends the implementation of a fluid management system to reduce MWF exposure.

The last priority (and least effective) are individual control measures: personal protective equipment, such as gloves, masks, overalls, etc.

Different guidelines provide help and instructions on how to work safely with MWFs, for example:

References

[1] Regulation (EU) No 528/2012 of the European Parliament and of the Council of 22 May 2012 concerning the making available on the market and use of biocidal products. Available at: https://echa.europa.eu/regulations/biocidal-products-regulation/legislation

[2] OECD, Organisation for Economic Co-operation and Development, Towards a Sustainable Use of Biocides, Series on Biocides No. 17, 2021. Available at https://one.oecd.org/document/ENV/CBC/MONO(2021)4/en/pdf

[3] PAN Germany – Pesticide Action Network Germany, ''The draft biocide regulation is not enough to adequately protect human and the environment'', Flyer, 2010, pp.1-2. Available at: http://www.pan-germany.org/download/biocides/fs_biocide_regulation.pdf

[4] Rossmore, H.W., ‘Introduction to Biocide use’. Handbook of Biocide and Preservative use. Blackie and Academic and Professional, Rossmore edit, 1995, p. 1.

[5] European Commission, ''Human exposure to biocidal products'', Technical Notes for Guidance TNsG, 2007, pp. 1-102. Available at: https://echa.europa.eu/documents/10162/983772/bpd_guid_tnsg-human-exposure-2007_en.pdf/3d59996f-b548-4bf0-876b-e04b5db04617

[6] Comité de coordination de toxicovigilance, ''Intoxications par les produits biocides. Données des centres antipoison et de toxicovigilance (1999-2009)'', Saisine de la Direction générale de la santé, à la demande du ministère chargé de l’écologie, 2010, pp. 1-67. Available at: https://centres-antipoison.net/biocides-2

[7] Centre Antipoisons. Toxicovigilance biocides 2020: Analyse de l'impact de l'épidémie de COVID-19 sur l'exposition aux désinfectants (TP1/TP2). Available at: https://www.health.belgium.be/sites/default/files/uploads/fields/fpshealth_theme_file/toxicovigilance_biocides_2020_fr.pdf

[8] European Commission, Directorate General for Health & Consumer, ''Research strategy to address the knowledge gaps on the antimicrobial resistance effects of biocides'', Scientific Committee on Emerging and Newly Identified Health Risks, SCENIHR, 2010, pp. 1-34. Available at: http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_028.pdf

[9] Reinert, D, Flaspöler, E., Hauke, A., Brun, E., Identification of emerging occupational safety and health risks, Safety Science Monitor, Issue 3, Vol. 1, Art. 3, 2007, p. 14.

[10] Johns Hopkins Bloomberg School of Public Health - news (2007). Poultry Workers at Increased Risk of Carrying Antibiotic-Resistant E. coli. Retrieved 19 Mai 2013, from: http://www.jhsph.edu/news/news-releases/2007/price-poultry-workers.html

[11] Randall L.P., Cooles S.W., Piddock L.J., Woodward M.J., ‘Effect of triclosan or a phenolic farm disinfectant on the selection of antibiotic-resistant Salmonella enteric’, ''J Antimicrob Chemother'', 2004, No 54, pp. 621-627.

[12] Regulation (EC) No 470/2009 of the European Parliament and of the Council of 6 May 2009 laying down Community procedures for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin, repealing Council Regulation (EEC) No 2377/90 and amending Directive 2001/82/EC of the European Parliament and of the Council and Regulation (EC) No 726/2004 of the European Parliament and of the Council. Available at: http://data.europa.eu/eli/reg/2009/470/oj

[13] Biocides Market Market by Type (Oxidizing Biocides, Non-Oxidizing Biocides), by Application (Water treatment, Personal care, Wood preservation, Paints and coating) and Region: Global Opportunity Analysis and Industry Forecast, 2021-2031. Available at https://www.alliedmarketresearch.com/biocides-market

[14] Buckle, A.P., Sharples, R., Prescott, C.V., Europe’s Biocidal Product Directive: Benefits and costs in urban pest management, Proceedings of the Fifth International Conference on Urban Pests, Chow-Yang Lee, William H. Robinson (edit.), 2005, pp.1-7. Available at: https://www.researchgate.net/publication/276950120_Europe%27s_biocidal_products_directive_benefits_and_costs_in_urban_pest_management

[15] Ziggers, D., Harmonisation needed for biocidal products, All about feed, Feed Tech, Vol 13, No.4, 2009. Available at: http://www.allaboutfeed.net/Home/General/2010/6/Harmonisation-needed-for-biocidal-products-AAF011482W/

[16] ECHA. Strategy to promote substitution to safer chemicals through innovation, 2018. Available at: https://echa.europa.eu/documents/10162/17228/250118_substitution_strategy_en.pdf/bce91d57-9dfc-2a46-4afd-5998dbb88500

[17] ECHA – European Chemical Agency (2012). Product Types. Available at: http://echa.europa.eu/regulations/biocidal-products-regulation/product-types

[18] Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. Available at: https://osha.europa.eu/en/legislation/directives/regulation-ec-no-1272-2008-classification-labelling-and-packaging-of-substances-and-mixtures

[19] Regulation (EC) No 1907/2006 - Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and establishing a European Chemicals Agency. Available at: https://osha.europa.eu/en/legislation/directives/regulation-ec-no-1907-2006-of-the-european-parliament-and-of-the-council

[20] 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. Available at: http://eur-lex.europa.eu/smartapi/cgi/sga_doc?smartapi!celexapi!prod!CELEXnumdoc&numdoc=31989L0391&model=guichett&lg=en

[21] Directive 2004/37/EC of 29 April 2004 on the protection of workers from the risks related to exposure to carcinogens or mutagens at work, available at: http://osha.europa.eu/en/legislation/directives/exposure-to-chemical-agents-and-chemical-safety/osh-directives/directive-2004-37-ec-indicative-occupational-exposure-limit-values

[22] Directive 98/24/EC - risks related to chemical agents at work of 7 April 1998 on the protection of the health and safety of workers from the risks related to chemical agents at work (fourteenth individual Directive within the meaning of Article 16(1) of Directive 89/391/EEC). Available at: https://osha.europa.eu/en/legislation/directives/75

[23] EU Commission. Commission Staff Working Document Accompanying the document Report from the Commission to the European Parliament and the Council on the implementation of Regulation (EU) No 528/2012 of the European Parliament and of the Council concerning the making available on the market and use of biocidal products. SWD/2021/128 final. Available at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A52021SC0128&qid=1662318792771

[24] bioexposure

[25] Durham, J., Working with Biocides, ''Workplace safety advice'', 13 Jan 2022. Available at: http://www.workplacesafetyadvice.co.uk/working-with-biocides.html

[26] Occupational Safety & Health Administration – OSHA, ''Metalworking Fluids: Safety and Health Best Practices Manual'', United States Department of Labor, 1999. Available at: http://www.osha.gov/SLTC/metalworkingfluids/metalworkingfluids_manual.html

[27] European Commission - Environment Directorate-General, ''Assessment of different options to address risks from the use phase of biocides'', Final report. 2009, pp. 1-131. Available at: https://ec.europa.eu/environment/archives/ppps/pdf/final_report0309.pdf

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