Press Area

Colistin is an antibiotic used in veterinary medicine, particularly in the livestock sector. In human medicine, because of its toxicity, it is only prescribed for the treatment of severe human infections involving bacteria resistant to all other therapeutic options (including bacteria resistant to last-generation cephalosporins and carbapenems). Because of the absence of any mechanism for transferring resistance to colistin between bacteria, recent opinions from both the European Medicines Agency (EMA) and ANSES have not previously recommended including colistin in the list of critically important antibiotics used in veterinary medicine. On 18 November 2015, the first transferable mechanism for resistance to colistin (the mcr-1 gene) was described in China in pigs and chickens, in meat sold at retail, and also among bacterial strains isolated in humans. In the light of this new scientific evidence, the EMA will convene its Antimicrobial Advice Ad Hoc Expert Group in order to revise its Opinion in the matter of the use of colistin in veterinary medicine, published in 2013. Accordingly, ANSES will revise the risk assessment it undertook in its scientific opinion on the classification of colistin as a veterinary antibiotic of critical importance. Colistin is an antibiotic used in veterinary medicine, particularly for treating colibacillosis infections in the livestock sector. In human medicine, colistin has long been avoided in therapeutic protocols because of renal toxicity. Since the global spread of resistance to last-generation cephalosporins and carbapenems, colistin has again come to be prescribed as an antibiotic for the treatment of severe human infections involving bacteria resistant to all other therapeutic options. Because of the renewed interest for colistin in human medicine, the scientific and medical community became concerned about the risk of the selection of resistance to colistin in humans, following its use in animals. Recent opinions published by both the European Medicines Agency (EMA) and ANSES recommended that colistin should not yet be included in the list of critically important antibiotics used in veterinary medicine, whose use requires supervision. In particular, the absence of a mechanism for transferring resistance to colistin between bacteria was a powerful scientific argument. November 2015: description of the first transferable mechanism for resistance to colistin On 18 November 2015, the first transferable mechanism for resistance to colistin (the mcr-1 gene) was described in China in pigs and chickens, in meat sold at retail, and also among bacterial strains isolated in humans 1 . The prevalence of this plasmidic gene has been estimated at approximately 20% in animals and around 1% in humans. The publication of the genetic sequence of the mcr-1 gene led several institutes to seek it in other bacterial collections around the world. To date, in Europe, the mcr-1 gene has been detected in bacterial strains of Escherichia coli and/or Salmonella enterica , by the European Reference Laboratory for Antimicrobial Resistance (DTU, Denmark) 2 , by the reference laboratory at Public Health England 3 and by the four ANSES laboratories involved in the monitoring of animal antimicrobial resistance 4 . In all these collections, the prevalence of the mcr-1 gene is particularly low. Moreover, no alarming increase in resistance to colistin in bacteria isolated from the poultry or pork sectors has been reported by the various ANSES surveillance networks in recent years. On 17 December 2015, additional data on the distribution of the mcr-1 gene in other world collections were published 4,5,6,7,8 . They confirm the low prevalence of this gene in humans and provide additional information about its molecular structure. Several studies are under way on this topic and several questions remain currently unanswered. They concern, most importantly: the prevalence of the mcr-1 gene in the different sectors, animals and humans, in France, in Europe and in the world. The different sampling programmes from the bacterial collections studied lead to the conclusion that the gene can be detected, but not yet at levels of prevalence validated from an epidemiological point of view. how long the mcr-1 gene has been circulating in animal and human bacterial flora. Most of the published data relate to relatively recent strains (post-2010). The length of time the gene has been circulating in livestock sectors is an important element of assessment in risk analysis. the levels of resistance to colistin (low or high) of bacteria possessing the mcr-1 gene, which directly affect its therapeutic impact. Also, the mcr-1 gene is not present in all colistin-resistant bacteria, which raises the question of the role played by this mechanism in a broader explanation of this resistance. the possibilities (or not) of co-selection of the mcr-1 gene by the use of antibiotics other than colistin, such as those widely used in veterinary medicine (e.g. tetracyclines, sulfonamides) or those of critical importance to humans and plasmid-mediated (last-generation cephalosporins). the diversity of the molecular characteristics of genetic supports (types of plasmids) and bacterial clones carrying the mcr-1 gene, on which depend the different capabilities of diffusion between bacterial species, between animal species, and from animals to humans. A new risk analysis is necessary related to the use of colistin The recently published scientific information on bacterial resistance to colistin will need to be taken into account in a new analysis of the risks related its use, especially in veterinary medicine. In this context, EMA has decided to convene its Antimicrobial Advice Ad Hoc Expert Group to revise its Opinion on the use of colistin in veterinary medicine, published in 2013. This Group includes experts from ANSES. For many years now, ANSES has played a key role in surveillance and alerts concerning phenomena of antimicrobial resistance in the animal world, and in connection with the possible consequences for public health. This work is carried out thanks to the responsiveness of all the schemes it runs, of regulatory monitoring at the slaughterhouse and in food, and in the framework of the activity of the Salmonella and Résapath networks that were set up several decades ago in France. In parallel, ANSES-ANMV, through its involvement with EMA and its annual survey on the consumption of veterinary antibiotics, provides essential data on the exposure of animals to antibiotics, which it is useful to compare with the levels of resistance observed. ANSES will therefore revise the risk assessment it undertook in its scientific opinion ( Opinion No 2015-SA-0118 , only in French) on the classification of colistin as a veterinary antibiotic of critical importance. Références Liu et al . Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2015; published online Nov 18. http://dx.doi.org/10.1016/S1473-3099(15)00424-7 Hasman et al . Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015. Eurosurveillance 2015; published online Dec 10. http://dx.doi.org/10.2807/15607917.ES.2015.20.49.30085 Public Health England (PHE). First detection of plasmid-mediated colistin resistance ( mcr-1 gene) in food and human isolates in England and Wales (Serial number 2015/090). London: Public Health England , 2015. Webb et al . Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 2015; published online Dec 17, 2015. http://dx.doi.org/10.1016/S1473-3099(15)00538-1 Arcilla et al . Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 2015; published online Dec 17, 2015. http://dx.doi.org/10.1016/S1473-3099(15)00541-1 Hu et al . Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 2015; published online Dec 17, 2015. http://dx.doi.org/10.1016/S1473-3099(15)00533- 2 Olaitan et al . Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 2015; published online Dec 17, 2015. http://dx.doi.org/10.1016/S1473-3099(15)00540-X Tse et al. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis 2015; published online Dec 17, 2015. http://dx.doi.org/10.1016/S1473-3099(15)00532-0

ANSES has published its conclusions on the risks to bees and other pollinators presented by insecticides based on neonicotinoids. It was asked to investigate this issue by the Ministers of Ecology, Agriculture and Health. The Agency recalls that in the absence of appropriate management measures, the use of neonicotinoids causes severe adverse effects in pollinator species.It emphasises the relevance of the European moratorium decided in 2013. It also notes that there is still a lack of knowledge concerning the impact of these products on bees and other pollinators. In its conclusions, the Agency first identifies all the uses for which the risk to honeybees, bumblebees and wild bees are considered to be low, subject to compliance with certain conditions of use. The Agency also emphasises that there is still considerable uncertainty concerning certain uses, in particular the treatment of seed for winter cereals or the spraying of orchards and vineyards. Pending the results of ongoing work at European level, the Agency recommends strengthening the conditions of use for all the uses about which there remains substantial uncertainty; it also recommends not planting a crop likely to attract pollinators immediately following a crop treated by neonicotinoids.

The Niort Laboratory, which specialises in diseases in ruminants, now has a new health mission contributing to the certification of French herds: it becomes the reference for detection of bovine hypodermosis (or "warble"). Bovine hypodermosis is a disease with a high economic impact, since it results in losses in dairy production, a significant degradation of animal hides, slower growth and occasional nervous disorders. This new mission supplements the laboratory's existing reference activities, in particular in the context of its two national and two international reference mandates. Located in the heart of a major cattle, sheep and goat farming area, the Niort Laboratory, co-financed by the Poitou-Charentes Region, carries out its main research missions on several viral, bacterial and parasitic diseases in ruminants that can have a high economic impact (such as herpesviruses, pestiviruses and paratuberculosis). Its work also focuses on resistance to anthelmintics used to treat intestinal strongyles in sheep and goats, and on animal welfare in the goat sector. Lastly, through its participation in the Observatory for Goat Diseases (OMACAP), the Laboratory contributes to the production of epidemiological data relating to the predominant health issues. All of its work is conducted in close collaboration with sector stakeholders, in particular within the Network of Excellence in Goat Production (Rexcap) and in a solid partnership established two years ago with GDS France. New recognition at national level The Niort Laboratory has had the mandate of National Reference Laboratory for infectious bovine rhinotracheitis since 2013 and for enzootic bovine leukosis since 2009. As such, it develops and validates the official analytical methods for the pathogens concerned and transfers them to the accredited laboratories. Furthermore, for the professionals represented by GDS France, the laboratory is also the expert laboratory responsible for the reference mission for bovine viral diarrhoea (BVD) and holds international mandates with the World Organisation for Animal Health (OIE) for retroviruses in small ruminants and paratuberculosis in ruminants. It now becomes responsible for the missions relating to its new mandate as National Reference Laboratory for bovine hypodermosis. Bovine hypodermosis or warble is a disease caused by the larvae of flies. These larvae, which come from eggs laid in summer in the limbs of cattle, pass through the skin and migrate through the body via either the oesophagus or the spinal cord. They emerge from the body through the animal's back, the following spring. In addition to the degradation of the hide that results from the larvae's exit, hypodermosis causes losses in dairy production, slower growth and sometimes nervous disorders. It has no impact on human health. The awarding of this new national reference mandate for bovine hypodermosis again testifies to the quality of the work of the Niort Laboratory and its commitment to ruminant health.

Following publication of the results of the assessment conducted at European level as part of the procedure to renew the approval granted to the active substance glyphosate, and the conflicting results of the International Agency for Research on Cancer (IARC) that concluded that this substance should be classified as "probably carcinogenic to humans", ANSES received a formal request to investigate the hazards posed by glyphosate to human health. In the Opinion it is publishing today, the Agency notes that in light of the limited level of evidence, it is not possible to propose a classification in Category 1A or 1B (respectively, known or presumed to be carcinogenic to humans, CLP Regulation), but that it could arguably be classified in Category 2 (substances suspected of being carcinogenic to humans, CLP). ANSES therefore believes that the classification of glyphosate should be rapidly reviewed by the European Chemicals Agency (ECHA). Besides the active substance, the co-formulants found in glyphosate preparations, tallowamine in particular, raise concerns. The Agency is therefore launching an assessment of the risks associated with the co-formulants found in all plant protection preparations, with priority given to glyphosate-based formulations. The Agency will also conduct an immediate reassessment of the marketing authorisations for preparations combining glyphosate and tallowamine.

Methylisothiazolinone (MIT) is a substance used as a preservative in many commercial mixtures such as detergents, paints and varnishes, and also in mixtures for professional use. It is also found in cosmetic products: its presence must then be mentioned on the packaging. Over the last few years, in France and elsewhere in Europe, an alarming increase in the number of cases of skin allergies to MIT has been observed. Work is currently being conducted on this substance with the aim of proposing a harmonised European classification under the CLP Regulation (on classification, labelling and packaging), as well as in the framework of the Regulation governing the marketing of biocidal products. In this context, ANSES issued an internal request to identify the categories of products entailing the most exposure, with a view to proposing recommendations to limit the exposure of people, whether or not they are already sensitised. In the Opinion it is publishing today, the Agency proposes stronger protection for consumers and workers in the framework of the regulatory work in progress at European level. Besides cosmetics and detergents, for which information is already mandatory, the Agency is recommending that information intended for the general population and professionals be systematically provided on the packaging of mixtures containing MIT. Lastly, ANSES is continuing its work to identify the sectors or jobs entailing the most exposure, with a view to better prevention and protection of exposed professionals. Methylisothiazolinone or MIT is mainly used for its preservative properties, particularly in paints and coatings, detergents, industrial processes, cosmetic products, etc. A recent study detected the presence of MIT in 93% of the paints tested. MIT can also be used for its fungicidal, bactericidal and disinfectant properties in a wide number of applications: varnishes, adhesives, detergents, textiles, etc. Over the last few years, in France and elsewhere in Europe, many publications have highlighted an alarming increase in the number of cases of skin allergies to this substance. In toxicological terms, MIT is recognised as a skin sensitiser, based on experimental data in animals and humans. Accordingly, following exposure to a high concentration of MIT, mainly via cosmetics, an allergic skin reaction may occur on re-exposure, even to low concentrations. In addition, the presence of MIT at high concentrations in many products for professional use is a cause of severe contact dermatitis in many professional categories. In this context, ANSES issued an internal request to conduct a review of the uses of MIT and describe the associated risks of dermal and respiratory sensitisation. The aim was to identify the categories of products entailing the most exposure, with a view to proposing possible recommendations to limit the exposure of people, whether or not they are already sensitised. The Agency’s recommendations In January 2015, a dossier for harmonised classification was submitted by Slovenia at European level in the framework of the "CLP" Regulation (on the classification, labelling and packaging of substances). This dossier proposes to classify MIT as a Category 1 skin sensitiser with a specific concentration limit of 0.06% (600 ppm). During the public consultation phase for this proposal, France indicated that it considered this limit of 600 ppm much too high in light of the available data and proposed a limit of 15 ppm. Other comments from European public institutions or Member States also support this view and propose a concentration limit offering greater protection. This proposal for classification is to be discussed shortly with all the Member States. The Agency also believes it is necessary to continue discussions at European level in the framework of the "Cosmetics" Regulation, in order to modify the concentrations of MIT as a preservative in cosmetic products. The Agency recommends that information intended for the general population and professionals be systematically provided on the packaging of mixtures containing MIT, regardless of the level of concentration in the mixture. This information is already mandatory for cosmetics and detergents. Providing, from the lowest concentration applicable, systematic information to the finished product as placed on the market, will enable sensitised individuals to avoid contact with the allergen. Moreover, as part of its work on the question of emissions of pollutants from construction materials, in 2009 ANSES had proposed a procedure for the qualification of volatile organic compound emissions. A lowest concentration of interest (LCI) had then been determined for MIT. This French value was also adopted by the European working group for the harmonisation of protocols and LCIs. In light of recent data, the Agency recommends taking MIT into account in the labelling specified for construction products, in order to inform consumers and workers about the emission levels of volatile pollutants. Lastly, the Agency is continuing its work on the analysis of occupational dermatitis in the framework of the National Network for Monitoring and Prevention of Occupational Diseases (RNV3P), which it coordinates. These studies will help describe the prevalence of these skin disorders according to the hazard, and identify the sectors or jobs at risk with a view to making recommendations for the implementation of appropriate preventive and protection measures in the workplace.

The World Health Organization recommends certain deltamethrin-impregnated mosquito nets to avoid the transmission of vector-borne diseases spread by mosquitoes. In France, these mosquito nets are not covered by any marketing authorisation, so they cannot be used in compliance with biocide regulations. In the context of the current Zika epidemic in the French départements of the Americas, the French High Council for Public Health recommends that France request a waiver from the European Union for the use of long-lasting deltamethrin-impregnated mosquito nets. In this context, ANSES has been asked by the Ministry of Ecology to urgently publish an opinion on the appropriateness of derogatory use of long-lasting deltamethrin-impregnated mosquito nets as provided for under Article 55.2 of the Biocidal Products Regulation. On the basis of available data, ANSES concludes that the use of such mosquito nets may be authorised. However, the Agency recommends attaching the net around the bed of infants and children so that it is difficult for them to reach, to ensure that they cannot put it into their mouths. It also recommends using mosquito nets whose efficacy has been validated by the World Health Organization and to restrict washes to a minimum given the toxicity of deltamethrin for the aquatic environment. Deltamethrin is an active biocidal substance approved within Europe to combat insects, mites and other arthropods. Deltamethrin-impregnated mosquito nets are recommended by the World Health Organization (WHO) to avoid the transmission of vector-borne diseases spread by mosquitoes. In France, long-lasting deltamethrin-impregnated mosquito nets are not covered by any marketing authorisation and cannot, therefore, be used. In the context of the current Zika epidemic in the French départements of the Americas, the French High Council for Public Health published an opinion on 18 January 2016 recommending that the competent French authority allow the derogatory use of deltamethrin-impregnated mosquito nets. ANSES was therefore requested by the French Ministry of Ecology to urgently publish an opinion on the appropriateness of derogatory use of deltamethrin-impregnated mosquito nets as provided for under Article 55.2 of the Biocidal Products Regulation. ANSES’s work ANSES based its work on WHO assessments as regards the technical characteristics and efficacy of long-lasting deltamethrin-impregnated mosquito nets. The use of nets meeting all WHO criteria should be preferred. These mosquito nets meet criteria of efficacy and resistance to washing, having proven effective after three years of use in the field. ANSES furthermore considers that despite mosquito resistance to deltamethrin, widely accepted in the literature and demonstrated in the French overseas départements , mosquito nets impregnated with a long-lasting insecticide still remain favourably effective to repel adult mosquitoes. The Agency’s recommendations On the basis of available data, in the opinion published today, ANSES considers that the risk related to the use of mosquito nets is acceptable for human health insofar as, for infants and young children, the mosquito net is attached around the bed so that children cannot grasp it and put it in their mouths. In addition, in the light of the highly toxic nature of deltamethrin for the aquatic environment, the Agency strongly recommends restricting the washing of nets to a minimum. As no data are available on the risk for human health and the environment and the efficacy of re-impregnation of nets with deltamethrin, ANSES does not recommend this practice. Finally, the Agency considers it necessary for the services responsible for distributing mosquito nets to inform users on the precautions to be taken as to their use and ensure the correct application of management measures. Currently, very few active larvicide and adulticide substances are used for vector control in France. The widespread use of deltamethrin, without alternating between other active substances, has led to the emergence of proven resistance among mosquitoes in the overseas départements . The agricultural and veterinary use of this compound accentuates this issue. There is therefore a vital need for a broader range of active substances not only in the short term but the medium term, because vector control actions against arbovirus and other pathogens are bound to spread throughout the French territory. Although authorised exceptionally by European regulations, the derogatory use of prohibited substances or products no longer appears a suitable and sustainable strategy. ANSES was asked on 3 June 2009 by the French Ministries of Ecology, Health and Labour to help select active substances that might be useful for vector control. In 2012, ANSES put forward a short-list of 32 active substances following multi-criteria analysis combining toxicity, eco-toxicity, exposure and environmental fate. These substances were then grouped into three classes corresponding to use in the short-, medium- or long-term. ANSES is today publishing an updated list of active substances that might be used for vector control with respect to their known usage and regulatory status within Europe. This is not a risk assessment but a list of active substances of interest that might be useful for vector control, upon which efforts should be concentrated in order to encourage manufacturers and foster research. ANSES also recommends developing efficacy trials and exposure models designed to estimate the exposure for operators, the general population and the environment, dedicated to the specific uses involved in vector control so as to conduct a detailed risk assessment and compare the different products.