Tarek Manasfi
email: tarek.manasfi@univ-amu.fr

Bruno Coulomb
email: bruno.coulomb@univ-amu.fr

Jean-Luc Boudenne
email: jean-luc.boudenne@univ-amu.fr

Jean - Luc

Occurrence, origin and toxicity of disinfection byproducts in chlorinated swimming pools: An overview

Disinfection treatments are critical to conserve the microbiological quality of swimming pool water and to prevent water-borne infections. The formation of disinfection byproducts (DBPs) in swimming pools is an undesirable consequence resulting from reactions of disinfectants (e.g. chlorine) with organic and inorganic matter present in pool water, mainly brought by bathers. A considerable body of occurrence studies has identified several classes of DBPs in swimming pools with more than 100 compounds detected, mainly in chlorinated freshwater pools.

Trihalomethanes (THMs), haloacetic acids (HAAs), haloacetaldehydes (HALs) are among the major DBPs in swimming pools. Other DBPs such as haloacetonitriles (HAN), haloamines, nitrosamines, and halobenzoquinones have also been detected. Researchers have been interested in identifying the precursors responsible for the formation of DBPs. In swimming pools, anthropogenic organic loads brought by swimmers increase the complexity of pool water chemistry. When human inputs (e.g. sweat, urine, hair, skin and personal care products) containing very diverse organic compounds are introduced to pools by swimmers, they react with chlorine resulting in the formation of complex mixtures of DBPs. The overwhelming majority of the total organic halide (TOX) content is still unknown in swimming pools. Exposure of swimmers to DBPs can take place through multiple routes, depending on the chemical properties of each DBP. Toxicological studies have shown that swimming pool water can be mutagenic with different potencies reported in different studies. Many DBPs have been shown to be genotoxic and carcinogenic. DBPs were also shown to induce reproductive and neurotoxic adverse effects in animal studies. Epidemiologic studies in humans have shown that exposure to DBPs increases the risk of respiratory adverse effects and bladder cancer. Association between DBPs and other health effects are still inconclusive. Data gathered in the present review (occurrence, toxicity, and toxicological reference values) could be used in conducting chemical risk assessment studies in swimming pools.

Introduction

Disinfection of drinking water was one of the major public health advances of the twentieth century. The adoption of water chlorination as a standard treatment technique caused a large drop in mortality from infectious disease around the world [START_REF] Boorman | Drinking water disinfection byproducts: review and approach to toxicity evaluation[END_REF]. The efficiency of chlorination in conserving the quality of drinking water from microbiological deterioration has contributed to the extrapolation of its application to include swimming pools and recreational water venues (WHO, 2006). Disinfection of swimming pool water is essential to kill pathogenic microorganisms and prevent outbreaks of infectious diseases (ANSES, 2012). Chlorination represents the most commonly used disinfection treatment in swimming pools [START_REF] Lakind | The good, the bad, and the volatile: Can we have both healthy pools and healthy people?[END_REF]. Chlorine can be added in the form of compressed chlorine gas, sodium hypochlorite solution (NaOCl), or solid calcium hypochlorite (Ca(OCl)2). Alternative disinfectants include other chlorine-based disinfectants (e.g. chlorine dioxide, stabilized chlorine), chloramines, and ozone. As in drinking water, disinfection of swimming pool water leads to the undesirable formation of disinfection byproducts (DBPs). Evidence from toxicological and epidemiological studies about adverse health effects for DBPs have raised concerns about the chemical safety of swimming pool waters. The first studies investigating the occurrence of DBPs in swimming pools date back to 1980 [START_REF] Beech | Nitrates, chlorates and trihalomethanes in swimming pool water[END_REF]Weil et al., 1980). Since then, many studies have been performed to examine the occurrence of DBPs in pools in different countries [START_REF] Aggazzotti | Survey of volatile halogenated organics (VHO) in Italy. Levels of VHO in drinking waters, surface waters and swimming pools[END_REF][START_REF] Chu | Distribution and determinants of trihalomethane concentrations in indoor swimming pools[END_REF][START_REF] Judd | Trihalomethane formation during swimming pool water disinfection using hypobromous and hypochlorous acids[END_REF][START_REF] Kim | Formation of disinfection by-products in chlorinated swimming pool water[END_REF]. Today, after more than 35 years of research, more than 100 DBP have been detected in swimming pools [START_REF] Chowdhury | Disinfection byproducts in swimming pool: Occurrences, implications and future needs[END_REF][START_REF] Daiber | Progressive Increase in Disinfection Byproducts and Mutagenicity from Source to Tap to Swimming Pool and Spa Water: Impact of Human Inputs[END_REF][START_REF] Richardson | What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water[END_REF][START_REF] Teo | Chemical contaminants in swimming pools: Occurrence, implications and control[END_REF]. The formation of DBPs in swimming pool waters is attributed to precursors that can be derived from the filling water as well as from pool users. Human inputs into swimming pools are diverse and include constituents of urine, sweat, rhino-pharyngeal secretions, skin particles, skin lipids (sebum), hair, cosmetics, sunscreens and other personal care products [START_REF] Keuten | Definition and quantification of initial anthropogenic pollutant release in swimming pools[END_REF][START_REF] Keuten | Quantification of continual anthropogenic pollutants released in swimming pools[END_REF][START_REF] Kim | Formation of disinfection by-products in chlorinated swimming pool water[END_REF][START_REF] Lakind | The good, the bad, and the volatile: Can we have both healthy pools and healthy people?[END_REF][START_REF] Richardson | What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water[END_REF][START_REF] Weisel | Childhood Asthma and Environmental Exposures at Swimming Pools: State of the Science and Research Recommendations[END_REF]. Chlorine, mainly in the form of hypochlorous acid and hypochlorite ions, reacts with these organic compounds resulting in the formation of complex mixtures of DBPs. Many classes of DBPs including haloamines, trihalomethanes (THMs), haloacetic acids (HAAs), haloacetonitriles (HANs), halodiacids, haloacetaldehydes (HALs), haloketones (HKs), haloaldehydes, haloamides, halophenols, halobenzoquinones and N-nitrosamines, have been identified in swimming pools [START_REF] Chowdhury | Disinfection byproducts in swimming pool: Occurrences, implications and future needs[END_REF][START_REF] Richardson | What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water[END_REF][START_REF] Teo | Chemical contaminants in swimming pools: Occurrence, implications and control[END_REF]Wang et al., 2013;[START_REF] Zwiener | Drowning in Disinfection Byproducts? Assessing Swimming Pool Water[END_REF]. However, the continuous inputs of organic loads by swimmers results in the formation of complex mixture of DBPs that have not been identified yet. In drinking water, more than 50% of the halogenated DBP material formed during chlorination are still not accounted for [START_REF] Krasner | Occurrence of a New Generation of Disinfection Byproducts[END_REF][START_REF] Richardson | Drinking Water Disinfection By-products[END_REF][START_REF] Weinberg | EPA The Occurrence of Disinfection By-Products (DBPs) of Health Concern in Drinking Water: Results of a Nationwide DBP Occurrence Study[END_REF]. Taking into consideration the complexity of anthropogenic inputs, the fraction of unidentified DBPs in swimming pools is even higher [START_REF] Kim | Formation of disinfection by-products in chlorinated swimming pool water[END_REF][START_REF] Lakind | The good, the bad, and the volatile: Can we have both healthy pools and healthy people?[END_REF][START_REF] Manasfi | Occurrence of brominated disinfection by-products in the air and water of chlorinated seawater swimming pools[END_REF]. The following sections present an overview of occurrence data for DBPs in swimming pools, the precursors that have been demonstrated to generate DBPs, and finally the toxicological and human health effects related to the exposure to DBPs.

Occurrence of DBPs in Swimming Pools

In the recent years, many studies have investigated the occurrence of DBPs in swimming pools.

The levels and nature of DBPs in swimming pools depend on several factors including the type of disinfectant, characteristics of the pool, pool users' hygiene [START_REF] Zwiener | Drowning in Disinfection Byproducts? Assessing Swimming Pool Water[END_REF], use of pools (competition, relaxation, recreational activities) [START_REF] Weng | Disinfection by-product dynamics in a chlorinated indoor swimming pool under conditions of heavy use : National swimming comptetition[END_REF][START_REF] Keuten | Quantification of continual anthropogenic pollutants released in swimming pools[END_REF], and nature of water used to fill the pools whether it is tap water, seawater or even thermal water (ANSES, 2013). Most of the studies analyzing the occurrence of DBPs investigated pools that were filled with municipal (tap) water and treated with chlorine [START_REF] Teo | Chemical contaminants in swimming pools: Occurrence, implications and control[END_REF]. Very few studies dealt with pools fed with seawater or with bromide-rich water [START_REF] Huang | Bromate ion formation in dark chlorination and ultraviolet/chlorination processes for bromide-containing waters[END_REF]Parinet et al., 2012;[START_REF] Manasfi | Identification of disinfection by-products in freshwatyer and seawater swimming pools and evaluation of genotoxicity[END_REF][START_REF] Font-Ribera | Environmental and personal determinants of the uptake of disinfection by-products during swimming[END_REF] or with pools treated with bromine for disinfection [START_REF] Lee | Production of various disinfection byproducts in indoor swimming pool waters treated with different disinfection methods[END_REF][START_REF] Hoffmann | Ozone-bromine treatment -Water treatment in public pools without chlorine : a new standard?[END_REF][START_REF] Chowdhury | Predicting bromide incorporation in a chlorinated indoor swimming pool[END_REF]. Two recent papers have reviewed the major disinfection by-products that have been commonly reported in chlorinated and brominated swimming pools [START_REF] Chowdhury | Disinfection byproducts in swimming pool: Occurrences, implications and future needs[END_REF][START_REF] Teo | Chemical contaminants in swimming pools: Occurrence, implications and control[END_REF]. The detected DBPs included haloamines, THMs, HAAs, haloaldehydes, halonitriles, haloketones (HKs), halonitromethanes, haloamides, haloalcohols, haloacids and other halogenated and nonhalogenated DBPs [START_REF] Chowdhury | Disinfection byproducts in swimming pool: Occurrences, implications and future needs[END_REF].

Haloamines

In terms of occurrence levels, chloramines (or bromamines in bromide-rich waters) are the disinfection by-products detected at the highest levels amongst DBPs, with monochloramine (NH2Cl) mainly found in water (up to 1180 µg L -1 ), followed by trichloramine (NCl3) (up to 800 µg L -1 ) and dichloramine (NHCl2) (up to 650 µg L -1 ) (Table 1). Trichloramine, which is four hundred-fold more volatile than its two congeners [START_REF] Chu | Occupational exposures of airborne trichloramine at indoor swimming pools in Taipei[END_REF], is also found in air with levels strongly inversely correlated to ventilation applied in indoor swimming pools [START_REF] Lévesque | Investigtaion of air quality problems in an indoor swimming pool : a case study[END_REF][START_REF] Gérardin | Modeling of variations in nitrogen trichloride concentration over time in swimming pool water[END_REF].

Table 1: Occurrence of haloamines in swimming pools around the world Chloramines are often determined as a global parameter (combined chlorine or total inorganic chloramines) by the use of the colorimetric N,N-diethyl-p-phenylenediamine (DPD). However, only membrane introduction mass spectrometry (MIMS) has demonstrated its performance not only to avoid interferences encountered using the DPD method (due to organic chloramines) [START_REF] Weaver | Volatile disinfection by-product analysis from chlorinated indoor swimming pools[END_REF] but also to discriminate the three inorganic chloramines (Kinani et al

2012

) and to analyze cyanogen halide compounds, such as cyanogen chloride (CNCl) and cyanogen bromide (CNBr) [START_REF] Yang | Quantification of aqueous cyanogen chloride and cyanogen bromide in environmental samples by MIMS[END_REF].

Trihalomethanes (THMs)

THMs have been detected at high concentrations in swimming pools, representing between 5 to 10% of total organohalogens as determined by the adsorbable organic halide (AOX) method, with chloroform (CHCl3) being the dominant species [START_REF] Aggazzotti | Survey of volatile halogenated organics (VHO) in Italy. Levels of VHO in drinking waters, surface waters and swimming pools[END_REF][START_REF] Beech | Nitrates, chlorates and trihalomethanes in swimming pool water[END_REF][START_REF] Erdinger | Pathways of trihalomethane uptake in swimming pools[END_REF][START_REF] Fantuzzi | Occupational exposure to trihalomethanes in indoor swimming pools[END_REF][START_REF] Lee | Characteristics of trihalomethane (THM) production and associated health risk assessment in swimming pool waters treated with different disinfection methods[END_REF][START_REF] Nieuwenhuijsen | Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review[END_REF][START_REF] Simard | Variability of chlorination by-product occurrence in water of indoor and outdoor swimming pools[END_REF][START_REF] Weaver | Volatile disinfection by-product analysis from chlorinated indoor swimming pools[END_REF], or bromoform (CHBr3) when bromide present in high concentrations or used as disinfectant [START_REF] Lourencetti | Trihalomethanes in chlorine and bromine disinfected swimming pools:air-water distributions and human exposure[END_REF]Parinet et al., 2012;[START_REF] Manasfi | Identification of disinfection by-products in freshwatyer and seawater swimming pools and evaluation of genotoxicity[END_REF]. THMs also include dichlorobromethane and bromodichloromethane. Table 2 gives an overview of the levels of THMs found in water and air of some swimming pools spread over the world.

Haloacetics acids (HAAs)

HAAs have also been detected as predominant DBPs (25 to 30% of total organohalogens, determined by the AOX method) with dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) occurring at the highest concentrations in most of the analyzed pools [START_REF] Cardador | Haloacetic acids in swimming pools: Swimmer and worker exposure[END_REF][START_REF] Lee | Production of various disinfection byproducts in indoor swimming pool waters treated with different disinfection methods[END_REF][START_REF] Sá | Analysis of haloacetic acids in water and air (aerosols) from indoor swimming pools using HS-SPME/GC/ECD[END_REF][START_REF] Wang | Haloacetic acids in swimming pool and spa water in the United States and China[END_REF][START_REF] Yeh | Bioanalytical and chemical evaluation of disinfection by-products in swimming pool water[END_REF] analyzed 39 outdoor and 15 indoor public pools in Canada and found that HAAs were higher in outdoor pools compared to indoor pools [START_REF] Simard | Variability of chlorination by-product occurrence in water of indoor and outdoor swimming pools[END_REF]. In bromide-rich waters, chlorinated

HAAs are shifted to their brominated analogues, with tribromoacetic acid (TBAA), chlorodibromoacetic acid (CDBAA) and dichlorobromoacetic acid (DCBAA) mostly found (Parinet et al., 2012;[START_REF] Manasfi | Occurrence of brominated disinfection by-products in the air and water of chlorinated seawater swimming pools[END_REF][START_REF] Manasfi | Identification of disinfection by-products in freshwatyer and seawater swimming pools and evaluation of genotoxicity[END_REF]. HAA concentrations reported in swimming pool water are always higher than those for THMs. This can be explained partially by the higher volatility of THMs as compared to HAAs (Table S1, in supporting information). In addition, the higher formation potential of bather organic loads to form HAAs than THMs and the stability of HAAs towards chlorine and pH variation tend to favor their accumulation in water [START_REF] Kanan | Formation of disinfection by-products in indoor swimming pool water: The contribution from filling water natural organic matter and swimmer body fluids[END_REF][START_REF] Lakind | The good, the bad, and the volatile: Can we have both healthy pools and healthy people?[END_REF]. Table 3 gives an overview of HAAs detected in chlorinated tap water swimming pools, chlorinated seawater swimming pools, and brominated swimming pools and spas.

Haloacetaldehydes (HALs)

HALs represent one of the major chemical class of DBPs found in swimming pools, accounting for 15 to 20% of total organohalogens, as determined by the AOX method (ANSES, 2011).

Among HALs, chloral hydrate (trichloroacetaldehyde, CH) is the most often encountered compound followed by dichloroacetaldehyde, in chlorinated swimming pools. CH is relatively stable in chlorinated swimming pools, with a hydrolysis rate of around 30% within 6-8 days at a pH of 7.6, resulting in chloroform and formic acid [START_REF] Freyfer | Sous-produits de chloration dans les eaux de piscine -Effet de l'ozonation[END_REF]. CH has been found in French swimming pools at levels varying from 31.8 and up to 497 µg L -1 (n=37; mean : 180.3 µg L -1 ; median: 118.9 µg.L -1 ) [START_REF] Freyfer | Sous-produits de chloration dans les eaux de piscine -Effet de l'ozonation[END_REF], in Korean Swimming pools between 5 and 35 µg L -1 [START_REF] Lee | Production of various disinfection byproducts in indoor swimming pool waters treated with different disinfection methods[END_REF], and in outdoor Australian swimming pools between 19.4 and 23.8 µg L -1 [START_REF] Yeh | Bioanalytical and chemical evaluation of disinfection by-products in swimming pool water[END_REF]. In chlorinated bromide-rich water or when bromine is used as disinfectant, bromal hydrate (BH) is the predominant trihaloacetaldehyde [START_REF] Daiber | Progressive Increase in Disinfection Byproducts and Mutagenicity from Source to Tap to Swimming Pool and Spa Water: Impact of Human Inputs[END_REF][START_REF] Manasfi | Occurrence of brominated disinfection by-products in the air and water of chlorinated seawater swimming pools[END_REF][START_REF] Manasfi | Identification of disinfection by-products in freshwatyer and seawater swimming pools and evaluation of genotoxicity[END_REF]. In a recent study, BH was detected as one of the degradation byproducts of benzophenone-3, a UV filter commonly used in sunscreens, in chlorinated swimming pools filled with seawater (Manasfi et al., 2015a). BH was detected in seawater swimming pools at low levels (0.35-2.22 µg L -1 ) (Manasfi et al., 2015b), probably due to its increased instability at the slightly basic pH of seawater (8.2-8.6) (Koudjonou and LeBel, 2006).

Haloacetonitriles (HANs)

The most commonly reported HANs include dichloroacetonitrile (DCAN, CNCHCl2), trichloroacetonitrile (TCAN, CNCCl3), bromochloroacetonitrile (BCAN, CNCHBrCl) and dibromoacetonitrile (DBAN, CNCHBr2). HANs are soluble substances, even if lipophilic, which are susceptible to degradation due to hydrolysis reaction or by reaction with the residual chlorine.

HANs are purgeable substances, so they are volatile, but they are less volatile than chloroform (Table S1). HANs are also byproducts of degradation of THMs and HAAs in certain conditions [START_REF] Weaver | Volatile disinfection by-product analysis from chlorinated indoor swimming pools[END_REF][START_REF] Lee | Production of various disinfection byproducts in indoor swimming pool waters treated with different disinfection methods[END_REF]. HAN production is directly related to the content of nitrogen compounds (urea, ammonium, creatine, amino acids) [START_REF] Li | Volatile disinfection byproduct formation resulting from chlorination of organic -Nitrogen precursors in swimming pools[END_REF][START_REF] Weaver | Volatile disinfection by-product analysis from chlorinated indoor swimming pools[END_REF]Deiber et al., 2016). DCAN and BCAN are the two compounds mostly encountered in freshwater swimming pools [START_REF] Tardif | Assessment of air and water contamination by disinfection by-products at 41 indoor swimming pools[END_REF]. DBAN is the predominant HAN in brominedisinfected swimming pools (Deiber et al., 2016) and in chlorinated seawater pools (Parinet et al., 2012;[START_REF] Manasfi | Occurrence of brominated disinfection by-products in the air and water of chlorinated seawater swimming pools[END_REF][START_REF] Manasfi | Identification of disinfection by-products in freshwatyer and seawater swimming pools and evaluation of genotoxicity[END_REF]. Table 4 presents HAN concentrations reported in swimming pools.

Table 4: Occurrence of haloacetonitriles (HAN) in swimming pools

Other (or emerging) DBPs

DBPs presented above account for the largest components of identified DBPs found in chlorinated swimming pools (by weight), as assessed by comparison of the sum of their concentrations with their adsorbable organic halide (AOX) concentrations [START_REF] Yeh | Bioanalytical and chemical evaluation of disinfection by-products in swimming pool water[END_REF].

However, few recent studies have revealed the presence of other compounds that could have a health impact, even at the ng L -1 level. Among these emerging compounds, nitrogenous DBPs are of the greatest concern for human health because of their higher genotoxicity, cytotoxicity, and carcinogenicity [START_REF] Richardson | What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water[END_REF]. Halonitromethanes (HNMs), including trichloronitromethane (TCNM or chloropicrin or nitrochloroform), bromonitromethane (BNM), bromochloronitromethane (BCNM) and dibromonitromethane (DBNM), have been detected in chlorinated swimming pools at concentrations between 0.8 and 7 µg L -1 , and up to 11 µg L -1 for BCNM (Kanan, 2010). Recently, TCNM was detected at levels varying between 0.07 and 1.43 µg L -1 [START_REF] Tardif | Assessment of air and water contamination by disinfection by-products at 41 indoor swimming pools[END_REF]. Among nitrosamines, N-nitrosodimethylamine (NDMA) has been reported in few studies at levels varying from 32 ng L -1 (Walse and Micth, 2008) to 210 ng L -1 (Kim and Han, 2011) and up to 310 ng L-1 in a hot tub [START_REF] Walse | Nitrosamine carcinogens also swim in chlorinated pools[END_REF]. NDMA has also been reported in Canada by [START_REF] Tardif | Assessment of air and water contamination by disinfection by-products at 41 indoor swimming pools[END_REF] with levels varying between 2.4 and 25.4 ng L -1 .

This compound may result either from the reaction between dichloramine and dimethylamine (present in urea and sweat), or by the reaction of N2O4 (resulting from the reaction of chlorine and nitrites) with dimethylamine [START_REF] Walse | Nitrosamine carcinogens also swim in chlorinated pools[END_REF]. Other nitrosamines (Nnitrosodiethylamine (NDEA), N-nitrosomorpholine (NMor), N-nitrosopyrrolidine (NPyr), Nnitrosopiperidine (NPip) and N-nitrosodibutylamine (NDBA) have also been reported but at very lower levels [START_REF] Teo | Chemical contaminants in swimming pools: Occurrence, implications and control[END_REF]. Cyanogen compounds (CNCl and CNBr) are also formed in swimming pools, due to the reaction of nitrogenous compounds of body fluids with chlorine, and from the reaction of chloramines with ammonium [START_REF] Lian | Volatile disinfection byproducts resulting from chlorination of uric acid: Implications for swimming pools[END_REF]. The reported levels ranged between 1 to 21 µg L -1 for CNCl and 1 to 25 µg L -1 [START_REF] Weaver | Volatile disinfection by-product analysis from chlorinated indoor swimming pools[END_REF]. Dichloromethylamine (DCMA, CH3NCl2) was detected as a byproduct of creatinine chlorination [START_REF] Li | Volatile disinfection byproduct formation resulting from chlorination of organic -Nitrogen precursors in swimming pools[END_REF]. DCMA was found in hot tub waters in USA by [START_REF] Weaver | Volatile disinfection by-product analysis from chlorinated indoor swimming pools[END_REF] at concentrations between 0.05 and 50.98 µg L -1 and in atmosphere of indoor pools in France at concentrations varying between 16 and 70 µg.m -3 [START_REF] Cimetiere | Henry's law constant of N,N-dichloromethylamine : application to the contamination of the atmosphere of indoor swimming pools[END_REF]. Recently, several halobenzoquinones were detected in chlorinated swimming pool waters (Wang et al., 2013).

Authors conducted chlorination experiments that showed that halobenzoquinones were formed from the chlorination of sunscreens and lotions. Very recently, an extensive study analyzed the occurrence of DBPs and the mutagenicity of water in pools and spas treated with chlorine, bromine or ozone [START_REF] Daiber | Progressive Increase in Disinfection Byproducts and Mutagenicity from Source to Tap to Swimming Pool and Spa Water: Impact of Human Inputs[END_REF]. Authors identified more than 100 DBPs including a new class of DBPs, bromoimidazoles. Occurrence data for these emerging DBPs in seawater pools are very limited.

Formation of DBPs in Swimming Pools

Reactivity of chlorine

Chlorine is used in the form of gaseous chlorine, liquid sodium hypochlorite (NaOCl), or solid calcium hypochlorite (Ca(OCl)2). The different forms of chlorine, when applied to water, generate hypochlorous acid (HOCl) which is a weak acid with a pKa of approximately 7.5 at 25 °C. The pH of water affects the dominating chlorine species such that HOCl dominates at pH below 7.5, while hypochlorite ions (OCl -) dominate at pH above 7.5. Of the two species, HOCl is the stronger oxidant (WHO, 2000). The reactivity of chlorine with inorganic compounds (e.g. ammonia, halides Br -and I -, Fe(II), As(III), Sulfates SO4 2-, CN -, NO2 -) usually results from an initial electrophilic attack. Reactions of chlorine with organic compounds may involve oxidation, addition, and electrophilic substitution reactions as possible pathways. However, only electrophilic attacks are significant from a kinetic point of view [START_REF] Deborde | Reactions of chlorine with inorganic and organic compounds during water treatment-Kinetics and mechanisms: A critical review[END_REF].

In water containing bromide ions, chlorination results in the formation of hypobromous acid, which is a weak acid (pKa = 8.7). The speciation of bromine between hypobromous acid and hypobromite ions depends on the pH of water. As a halogenating agent, bromine is usually more reactive than chlorine especially with phenolic compounds leading to the formation of brominated products [START_REF] Acero | Kinetics and mechanisms of formation of bromophenols during drinking water chlorination: Assessment of taste and odor development[END_REF][START_REF] Gallard | Rate constants of reactions of bromine with phenols in aqueous solution[END_REF][START_REF] Hua | Effect of Bromide and Iodide Ions on the Formation and Speciation of Disinfection Byproducts during Chlorination[END_REF]. Thus, bromide levels, pH, and other factors (e.g. temperature, organic content) can affect the composition and levels of DBPs in chlorinated swimming pools [START_REF] Teo | Chemical contaminants in swimming pools: Occurrence, implications and control[END_REF]WHO, 2000) Precursors of DBPs in swimming pools

Natural organic matter

Natural organic matter (NOM) was the first known precursors to be accounted for the formation of DBPs in chlorinated drinking waters [START_REF] Bellar | The Occurrence of Organohalides in Chlorinated Drinking Waters (PDF)[END_REF][START_REF] Rook | Formation of haloforms during chlorination of natural waters[END_REF]. Similar to drinking water, DBPs can be formed from reactions of chlorine with NOM present in the filling water of swimming pools [START_REF] Chowdhury | Disinfection byproducts in swimming pool: Occurrences, implications and future needs[END_REF][START_REF] Kanan | Formation of disinfection by-products in indoor swimming pool water: The contribution from filling water natural organic matter and swimmer body fluids[END_REF]. These reactions result in the formation of THMs, HAAs, HANs, HKs, and halofuranones [START_REF] Urbansky | Analyzing Drinking Water for Disinfection Byproducts[END_REF]. [START_REF] Kanan | Formation of disinfection by-products in indoor swimming pool water: The contribution from filling water natural organic matter and swimmer body fluids[END_REF] conducted a comparative formation potential study and showed that NOM in chlorinated swimming pools formed more THMs than HAAs.

Body fluids released by swimmers

Human body fluids are believed to be major precursors for the formation of DBPs in swimming pools [START_REF] Kim | Formation of disinfection by-products in chlorinated swimming pool water[END_REF]. It has been estimated that a swimmer releases approximately 25-77 mL in average [START_REF] De Laat | Concentration levels of urea in swimming pool water and reactivity of chlorine with urea[END_REF][START_REF] Weng | Effects of UV 254 irradiation on residual chlorine and DBPs in chlorination of model organic-N precursors in swimming pools[END_REF]. In addition, Seux (1985) estimated that every swimmer introduces into the pool 100 to 1000 ml/h of sweat depending on the physical activity.

Nitrogen-containing DBPs are generally attributed to nitrogenous organic precursors present in human body fluids (mainly urine and sweat) such as uric acid, urea, creatinine, L-arginine, Lhistidine, glycine, and ammonia [START_REF] Lian | Volatile disinfection byproducts resulting from chlorination of uric acid: Implications for swimming pools[END_REF][START_REF] Weng | Effects of UV 254 irradiation on residual chlorine and DBPs in chlorination of model organic-N precursors in swimming pools[END_REF]. The reaction pathways leading to the formation of DBPs from the chlorination of these organic compounds have been previously identified [START_REF] Blatchley | Reaction mechanism for chlorination of urea[END_REF][START_REF] De Laat | Concentration levels of urea in swimming pool water and reactivity of chlorine with urea[END_REF][START_REF] Freuze | Effect of chlorination on the formation of odorous disinfection by-products[END_REF][START_REF] Hureiki | Chlorination studies of free and combined amino acids[END_REF][START_REF] Jafvert | Reaction scheme for the chlorination of ammoniacal water[END_REF][START_REF] Joo | Nitrile, aldehyde, and halonitroalkane formation during chlorination/chloramination of primary amines[END_REF][START_REF] Li | Volatile disinfection byproduct formation resulting from chlorination of organic -Nitrogen precursors in swimming pools[END_REF][START_REF] Na | Mechanism and kinetics of cyanogen chloride formation from the chlorination of glycine[END_REF]. Trichloramine has been identified as a byproduct of chlorination of organic nitrogenous compounds present in body fluids [START_REF] Li | Volatile disinfection byproduct formation resulting from chlorination of organic -Nitrogen precursors in swimming pools[END_REF][START_REF] Lian | Volatile disinfection byproducts resulting from chlorination of uric acid: Implications for swimming pools[END_REF]. The highly toxic cyanogen chloride (CNCl) has been identified as a byproduct of chlorination of glycine [START_REF] Lee | Cyanogen chloride precursor analysis in chlorinated river water[END_REF][START_REF] Li | Volatile disinfection byproduct formation resulting from chlorination of organic -Nitrogen precursors in swimming pools[END_REF] and uric acid [START_REF] Lian | Volatile disinfection byproducts resulting from chlorination of uric acid: Implications for swimming pools[END_REF]. L-Histidine was found to act as precursor for the formation of dichloroacetonitrile (DCAN) and slightly to the formation of CNCl. Besides nitrogenous DBPs, reactions of chlorine with human body fluids also generates non-nitrogenous DBPs including HAAs, THMs, THA, and HK [START_REF] Kim | Formation of disinfection by-products in chlorinated swimming pool water[END_REF].

Formation potential studies conducted on body fluid analogs showed their tendency to form more HAAs than THMs [START_REF] Kanan | Formation of disinfection by-products in indoor swimming pool water: The contribution from filling water natural organic matter and swimmer body fluids[END_REF].

Particles released by swimmers

The potential of particles (e.g. skin cells, hair, and microorganisms) to form DBPs in swimming pools has been first demonstrated by [START_REF] Kim | Formation of disinfection by-products in chlorinated swimming pool water[END_REF]. Recently, Hansen et al. (2012b) examined the potential of particles captured by filters in swimming pools to form DBPs. The particles were collected from hot tubs and treated with chlorine in laboratory-controlled experiments. The formation of DBPs from human particles was found to be higher than that reported from other precursors including body fluid analogues (BFA) and natural organic matter (Table S2), probably due to high contents of nitrogenous precursors present in human particles. However, the formation of DBPs from particles released by bathers still merit further research since particles studied in previous investigations have not been fully characterized and discriminated. In the previously conducted studies, there has been no separation of skin and hair particles from microorganisms which themselves have been already shown to acts as precursors for DBPs (Wang et al., 2013).

Table S2: DBP formation from different chlorinated precursors at pH 7.0

Emerging precursors in swimming pools

Advances in analytical methods have allowed to detect and measure many emerging organic compound originating from human inputs in swimming pools [START_REF] Richardson | Water Analysis: Emerging Contaminants and Current Issues[END_REF].

Most of these compounds are ingredients of personal care products (PCPs) and sometimes of pharmaceuticals. Personal care products (PCPs) constitute a diverse group of products including lotions, sunscreens, perfumes, and cosmetic creams. Since PCPs are applied externally on the human body, their ingredients can be released upon immersion of swimmers into water. Among the ingredients that can be found in PCPs, there are disinfectants (e.g. triclosan), fragrances (e.g. musks), insect repellants (e.g. DEET), preservatives (e.g. parabens) and UV filters (e.g. methylbenzylidene camphor) [START_REF] Ternes | Peer Reviewed: Scrutinizing Pharmaceuticals and Personal Care Products in Wastewater Treatment[END_REF]. Parabens or their salts, which are widely used as preservatives in pharmaceuticals and PCPs, have been detected and quantified in swimming pool waters [START_REF] Alcudia-León | Determination of parabens in waters by magnetically confined hydrophobic nanoparticle microextraction coupled to gas chromatography/mass spectrometry[END_REF][START_REF] Terasaki | Determination of chlorinated by-products of parabens in swimming pool water[END_REF]. In addition, several pharmaceutical compounds including atenolol, carbamazepine, hydrochlorothiazide, metronidazole, ofloxacin, sulfamethoxazole, acetaminophen, ibuprofen, ketoprofen and phenazone were detected in swimming pools and spas in Spain [START_REF] Ekowati | Occurrence of pharmaceuticals and UV filters in swimming pools and spas[END_REF]. Teo et al.

(2016) reported the detection of ibuprofen and caffeine in Australian swimming pools. Urination in swimming pools can be a potential route for pharmaceuticals into the pool water, especially that certain pharmaceutical are secreted unchanged in urine [START_REF] Richardson | The fate of pharmaceutical chemicals in the aquatic environment[END_REF][START_REF] Weng | The Presence of Pharmaceuticals and Personal Care Products in Swimming Pools[END_REF]. Recently, Sharifan et al. ( 2016) estimated that considerable amounts of UV filters are introduced into pools, prompting a call for an urgent investigation regarding the potential toxic effects of UV filter transformation products and DBPs originating from them.

Organic UV filters are increasingly used due to concerns about adverse health effects of exposure to sunlight. Organic UV filters can be found in sunscreens and in other PCPs, such as cosmetics, beauty creams, skin lotions, lipsticks, hair sprays, hair dyes, and shampoos [START_REF] Ramos | Advances in analytical methods and occurrence of organic UV-filters in the environment -A review[END_REF][START_REF] Díaz-Cruz | Organic UV filters and their photodegradates, metabolites and disinfection by-products in the aquatic environment[END_REF]. Several studies conducted in different countries have reported the occurrence of UV filters in swimming pools. The concentrations of UV filters occurring in the pools varied considerably between different surveys with detected levels ranging from the sub nanogram to the microgram per liter orders [START_REF] Ekowati | Occurrence of pharmaceuticals and UV filters in swimming pools and spas[END_REF][START_REF] Lambropoulou | Gas chromatographic determination of 2-hydroxy-4-methoxybenzophenone and octyldimethyl-< i> p</i>-aminobenzoic acid sunscreen agents in swimming pool and bathing waters by solid-phase microextraction[END_REF][START_REF] Zwiener | Drowning in Disinfection Byproducts? Assessing Swimming Pool Water[END_REF]. The levels of UV filters quantified in pools in different countries so far are summarized in Table 5. PCPs and other emerging contaminants, similarly to other organic precursors, react with chlorine leading to the formation of DBPs. For this reason, the occurrence of pharmaceuticals and PCPs in swimming pool waters has raised concerns about their potentially toxic byproducts [START_REF] Bottoni | Emerging issues on degradation by-products deriving from personal care products and pharmaceuticals during disinfection processes of water used in swimming pools[END_REF]. Although several studies have analyzed the occurrence of these compounds in swimming pools, data about their degradation and transformation products in chlorinated media are very limited. [START_REF] Shen | Demonstration of 20 pharmaceuticals and personal care products (PPCPs) as nitrosamine precursors during chloramine disinfection[END_REF] demonstrated the potential of a group of pharmaceuticals and PCPs containing amine groups to serve as nitrosamine precursors during disinfection. [START_REF] Kuhlich | Transformations of polycyclic musks AHTN and HHCB upon disinfection with hypochlorite: two new chlorinated disinfection by-products (CDBP) of AHTN and a possible source for HHCB-lactone[END_REF] investigated the reactions of chlorine with the two polycyclic musks 6-acetyl-1,1,2,4,4,7-hexamethyltetraline (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopentag-2-benzopyran (HHCB), widely used as fragrances in cosmetics. AHTN chlorination generated two new chlorinated DBPs. Studies on the fate of UV filters in chlorinated waters such as swimming pools are rather scarce [START_REF] Santos | The degradation products of UV filters in aqueous and chlorinated aqueous solutions[END_REF]. [START_REF] Sakkas | Aqueous photolysis of the sunscreen agent octyl-dimethyl-p-aminobenzoic acid[END_REF] studied the behavior of the UV filter octyl-dimethyl-p-aminobenzoic acid (ODPABA) in various aqueous solutions and identified several chlorinated byproducts originating from the UV filter. [START_REF] Negreira | Study of some UV filters stability in chlorinated water and identification of halogenated by-products by gas chromatography-mass spectrometry[END_REF] investigated the fate of the UV filters ethylhexyl salicylate (EHS), ODPABA, and 2-hydroxy-4-methoxybenzophenone (BP-3, OXY) in chlorinated aqueous solutions. EHS showed an acceptable stability whereas BP-3 and ODPABA reacted with free chlorine at significant rates following pseudo-first-order kinetics. The reaction of chlorine with OXY and ODPABA involved electrophilic aromatic substitutions.

Monohalogenated and dihalogenated byproducts of OXY were detected. Halogenated 3methoxyphenol was also detected as a cleavage byproduct. filters were rapidly transformed by aqueous chlorine in a second-order reaction, first order with respect to each reactant. Authors detected chloroform as a stable transformation product resulting from the reaction of chlorine with OXY and DIOXY. Chloroform yields at pH 8 were 0.221 and 0.212 for OXY and DIOXY, respectively. These yields are similar to the average yields for phenols and substituted phenols [START_REF] Gallard | Chlorination of phenols: Kinetics and formation of chloroform[END_REF]. Wang et al. (2013) found that some sunscreens and PCPs produced halobenzoquinones when chlorinated swimming pool water. [START_REF] Li | Transformation of benzophenone-type UV filters by chlorine: Kinetics, products identification and toxicity assessments[END_REF] studied the reactivity of a group of benzophenone-type UV filters with chlorine in aqueous solutions. Second-order reactions were found to take place between chlorine and the UV filters OXY, 4-hydroxybenzophenone, and 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid.

Authors identified several transformation products and proposed transformation pathways that include electrophilic substitutions, methoxyl substitutions, ketone group oxidations, hydrolysis, decarboxylation, and ring cleavage reactions. Authors also tested the toxicity of the chlorinated UV filters on the luminescent bacteria Photobacterium phosphoreum. Most of the UV filters exhibited higher toxicities after chlorination.

Toxicity and Human Health Effects of DBPs

Swimming pool users can be exposed to DBPs through multiple routes: dermal absorption, inhalation, and ingestion [START_REF] Chowdhury | Disinfection byproducts in swimming pool: Occurrences, implications and future needs[END_REF][START_REF] Zwiener | Drowning in Disinfection Byproducts? Assessing Swimming Pool Water[END_REF]. Many in vitro and in vivo toxicological studies have provided evidence about toxic effects induced by DBPs.

Epidemiological studies have suggested associations between exposure to DBPs and adverse health effects in humans.

Toxicological studies

Toxicity of pool waters

Few studies have analyzed the mutagenic potential of swimming pool water. [START_REF] Honer | Mutagenic activity of swimming-pool water[END_REF] assessed the mutagenic potential of water samples obtained from three public indoor pools in Canada and detected positive mutagenic activity using the Ames test in Salmonella typhimurium TA100. [START_REF] Richardson | What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water[END_REF] tested the mutagenicity of water samples obtained from brominated and chlorinated pools. Samples of both pools exhibited mutagenic activity similar to the average mutagenicity of drinking waters. [START_REF] Glauner | Swimming pool water -Fractionation and genotoxicological characterization of organic constituents[END_REF] evaluated the genotoxicity of different fractions of DBPs present in swimming pool water and found that the strongest mutagenic activity was induced by the low-molecular-weight fraction. [START_REF] Liviac | Genotoxicity of water concentrates from recreational pools after various disinfection methods[END_REF] analyzed the genotoxicity of water concentrates of recreational pools under different disinfection treatments and that of source tap water used in filling the pools. Authors detected higher genotoxic activity induced by the recreational pool water compared to source tap water. Plewa et al. (2011) compared the mammalian cell cytotoxity of various recreational pool water samples issued from the same tap water source and showed that the whole disinfected waters samples (indoor and outdoor) were more cytotoxic than raw water. [START_REF] Daiber | Progressive Increase in Disinfection Byproducts and Mutagenicity from Source to Tap to Swimming Pool and Spa Water: Impact of Human Inputs[END_REF] studied the progressive increase of water mutagenicity from tap water to swimming pool and spa waters, disinfected by chlorine, ozone or bromine, using the Salmonella assay. In this latter study, the mutagenicity correlated very well with the heavy use of pools, and therefore with the levels of DBPs (especially the nitrogenous brominated compounds).

Toxicity of DBPs

Numerous studies have investigated the toxicological effects induced by DBPs. However, most of these studies focused on few toxicity endpoint, mainly genotoxicity, carcinogenicity, and reproductive effects [START_REF] Villanueva | Overview of Disinfection By-products and Associated Health Effects[END_REF]. Experimental evidence has been provided in many investigations regarding the genotoxicity of numerous DBPs [START_REF] Guha | Carcinogenicity of trichloroethylene, tetrachloroethylene, some other chlorinated solvents, and their metabolites[END_REF][START_REF] Villanueva | Overview of Disinfection By-products and Associated Health Effects[END_REF]. [START_REF] Richardson | Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research[END_REF] reviewed comprehensively the reported data about the genotoxicity and carcinogenicity of 85 DBPs. Table 6 summarizes of well-documented genotoxic and/or carcinogenic effects of THMs, HAAs, and trihaloacetaldehydes (ANSES, 2011). Table S3 presents the known Toxicological Reference Values (TRV) of several DBPs, defined as priority substances to be monitored in French swimming pools (ANSES, 2011). Generally, N-containing DBPs exhibit higher genotoxic potencies than C-containing DBPs [START_REF] Muellner | Haloacetonitriles vs. regulated haloacetic acids: Are nitrogen-containing DBFs more toxic?[END_REF][START_REF] Plewa | Comparative mammalian cell toxicity of N-DBPs and C-DBPs. Disinfection By-Products in Drinking Water[END_REF]. Furthermore, brominated DBPs are more genotoxic than the chlorinated compounds, while iodinated DBPs were the most genotoxic of all [START_REF] Jeong | Occurrence and Comparative Toxicity of Haloacetaldehyde Disinfection Byproducts in Drinking Water[END_REF][START_REF] Plewa | Mammalian cell cytotoxicity and genotoxicity of the haloacetic acids, a major class of drinking water disinfection byproducts[END_REF][START_REF] Plewa | Mammalian cell cytotoxicity and genotoxicity analysis of drinking water disinfection by-products[END_REF][START_REF] Richardson | Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research[END_REF][START_REF] Yang | Toxic Impact of Bromide and Iodide on Drinking Water Disinfected with Chlorine or Chloramines[END_REF]. In a recent study, CH was shown not to induce genotoxic effects, while BH induced mutations and DNA damage but not chromosomal aberrations (Manasfi et al., 2017a). [START_REF] Jeong | Occurrence and Comparative Toxicity of Haloacetaldehyde Disinfection Byproducts in Drinking Water[END_REF] compared the toxicity of six DBP classes by assessing their cytotoxicities to chinese hamster ovary (CHO) cells. The rank order of cytotoxicity was haloacetamides > HALs > halonitromethanes > HAAs > HANs > THMs. Among HALs the rank order of cytotoxicity was tribromoacetaldehyde (TBAL)

≈ chloroacetaldehyde (CAL) > dibromoacetaldehyde (DBAL) ≈ bromochloroacetaldehyde (BCAL) ≈ dibromochloroacetaldehyde (DBCAL) > IAL (iodoacetaldehyde) > bromoacetaldehyde (BAL) ≈ bromodichloroacetaldehyde (BDCAL) > dichloroacetaldehyde (DCAL) > trichloroacetaldehyde (TCAL). However, despite these studies, there are still data gaps with regard to the cytotoxicity and genotoxicity of DBPs [START_REF] Richardson | Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research[END_REF][START_REF] Richardson | Drinking Water Disinfection By-products[END_REF]. Experiments conducted in vivo have shown that certain DBPs are carcinogenic [START_REF] Boorman | Drinking water disinfection byproducts: review and approach to toxicity evaluation[END_REF][START_REF] Melnick | Toxicity and carcinogenicity of the water disinfection byproduct, dibromoacetic acid, in rats and mice[END_REF][START_REF] Richardson | Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research[END_REF]. In addition, investigations conducted in animals have provided evidence about the potential of DBPs to induce a range of adverse reproductive effects such as reduced fetal growth, sperm toxicity, and teratogenicity [START_REF] Tardiff | Updated weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection byproducts[END_REF]. Few studies focused on the neurotoxicity of DBPs. Dichloroacetic acid (DCAA) and dibromoacetic acid (DBAA) were found to induce neurotoxic effects in rats [START_REF] Moser | Neurotoxicity Produced by Dibromoacetic Acid in Drinking Water of Rats[END_REF][START_REF] Moser | Behavioral Evaluation of the Neurotoxicity Produced by Dichloroacetic Acid in Rats[END_REF]. More recently, THMs and tetrachloroethylene were shown to induce autistic-like behaviors in male mice [START_REF] Guariglia | Chlorination byproducts induce gender specific autistic-like behaviors in CD-1 mice[END_REF]. HAAs have been identified as being genotoxic and cytotoxic and able to induce cellular DNA damage and oxidative stress response via several pathways. Some toxicological studies showed that HAAs are more carcinogenic than THMs with DCAA and TCAA producing liver tumors in rodents [START_REF] Righi | Brmate, chlorite, chlorate, haloacetic acids, and trihalomethanes in indoor swimming pool waters in Italy[END_REF]. DCAA has been classified by IARC as possibly carcinogenic to humans (group 2B). Moreover, DCAA and TCAA induce both developmental and teratogenic effects in rats including low birthweight, cardiovascular and urogenital malformations and reproductive effects, such as lower sperm numeration [START_REF] Righi | Brmate, chlorite, chlorate, haloacetic acids, and trihalomethanes in indoor swimming pool waters in Italy[END_REF].

Epidemiological studies in Humans

Respiratory effects

Several epidemiological studies have investigated the respiratory effects of chronic swimming pool attendance for workers, elite swimmers, and children. Exposure to DBPs was associated with higher prevalence of adverse respiratory effects among pool workers [START_REF] Fantuzzi | Prevalence of ocular, respiratory and cutaneous symptoms in indoor swimming pool workers and exposure to disinfection by-products (DBPs)[END_REF][START_REF] Jacobs | Exposure to trichloramine and respiratory symptoms in indoor swimming pool workers[END_REF][START_REF] Massin | Respiratory symptoms and bronchial responsiveness in lifeguards exposed to nitrogen trichloride in indoor swimming pools[END_REF]. Some studies have described higher prevalence of asthma among elite swimmers [START_REF] Fisk | Asthma in swimmers: a review of the current literature[END_REF]. Some surveys have demonstrated associations between regular attendance at chlorinated pools and increased risk of asthma in children [START_REF] Bernard | Chlorinated pool attendance, atopy, and the risk of asthma during childhood[END_REF][START_REF] Bernard | Lung hyperpermeability and asthma prevalence in schoolchildren: unexpected associations with the attendance at indoor chlorinated swimming pools[END_REF]Langerkvist et al., 2004;[START_REF] Nickmilder | Ecological association between childhood asthma and availability of indoor chlorinated swimming pools in Europe[END_REF]. Also, investigations have suggested increased risk of recurrent respiratory tract infections and otitis media linked to baby swimming [START_REF] Nystad | Baby swimming increases the risk of recurrent respiratory tract infections and otitis media[END_REF]. Exposure to trichloramine, a volatile irritant DBP in indoor pools, has often been associated with an increased risk of respiratory effects in highly exposed populations [START_REF] Florentin | Health effects of disinfection by-products in chlorinated swimming pools[END_REF][START_REF] Villanueva | Overview of Disinfection By-products and Associated Health Effects[END_REF]. Recent studies clearly demonstrated uptake of DBPs during swimming, by measuring levels of THMs in exhaled breath of swimmers, before (0.5 µg.m -3 , median level found in 116 bathers) and after swimming (14.4 µg.m -3 , median level). Moreover, a direct correlation between levels of brominated THMs measured in air levels found in exhaled breath was detected, despite variations observed according to sex, physical activity and polymorphisms in key metabolic enzymes [START_REF] Marco | Influence of physical activity in the intake of trihalomethanes in indoor swimming pools[END_REF]Font-Ribera et al., 20 2016). Exposure of swimmers and workers to THMs had been also previously reported in several past studies (Caro and Gallego, 2008;Kogevinas et al., 2010;[START_REF] Lourencetti | New method for determination of trihalomethanes in exhaled breath : applicaions to swimming pool and bath environments[END_REF][START_REF] Nieuwenhuijsen | Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review[END_REF][START_REF] Xu | Dermal uptake of chloroform and haloketones during bathing[END_REF]. However, some studies have claimed that swimming is beneficial for children and adolescents with asthma [START_REF] Matsumoto | Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma[END_REF][START_REF] Rosimini | Benefits of Swim Training for Children and Adolescents with Asthma[END_REF]. Current evidence of an association between childhood swimming and new-onset asthma is suggestive but not conclusive [START_REF] Weisel | Childhood Asthma and Environmental Exposures at Swimming Pools: State of the Science and Research Recommendations[END_REF]. Inconsistent findings have been continuously reported in studies that are more recent. In a prospective longitudinal epidemiologic study, no significant association was found between increased risk of asthma or allergic symptoms and swimming pool attendance in British children. The study suggested that swimming was associated with increased lung function and lower risk of asthma symptoms, especially among children with preexisting respiratory conditions [START_REF] Font-Ribera | Swimming Pool Attendance, Asthma, Allergies, and Lung Function in the Avon Longitudinal Study of Parents and Children Cohort[END_REF]. On the other hand, a more recent study conducted in Sweden supported the proposed link between indoor swimming pool attendance and asthma in sensitized children [START_REF] Andersson | Swimming pool attendance is related to asthma among atopic school children: a populationbased study[END_REF].

Further well-designed studies with defined asthma outcomes are still needed to provide conclusive evidence about the relationship between swimming pool attendance and childhood asthma.

Cancer

Several epidemiological studies have demonstrated evidence for a relationship between exposure to DBPs and increased risks of bladder cancer [START_REF] Cantor | Polymorphisms in GSTT1, GSTZ1, AND CYP2E1, disinfection by-products, and risk of bladder cancer in Spain[END_REF][START_REF] Nieuwenhuijsen | Health impacts of long-term exposure to disinfection by-products in drinking water in Europe: HIWATE[END_REF][START_REF] Villanueva | Disinfection Byproducts and Bladder Cancer[END_REF]. Two studies evaluated specifically the exposure to DBPs through swimming pool attendance and found increased risk of bladder cancer among attending subjects mainly related to THM exposure through showering, bathing, and swimming [START_REF] Villanueva | Bladder cancer and exposure to water disinfection byproducts through ingestion, bathing, showering, and swimming in pools[END_REF]. [START_REF] Panyakapo | Cancer risk assessment from exposure to trihalomethanes in tap water and swimming pool water[END_REF] showed that the risk of developing cancer exists in swimmers exposed to THM from pool and tap water, and that the dermal route accounts for 94.2% of the total THM exposure for swimmers. Some studies have suggested associations between exposure to DBPs and other types of cancer including colorectal and skin cancer [START_REF] Nelemans | Swimming and the risk of cutaneous melanoma[END_REF][START_REF] Rahman | Disinfection by-products in drinking water and colorectal cancer: a meta-analysis[END_REF]. However, evidence about such associations remains inconclusive and inconsistent [START_REF] Hrudey | Chlorination disinfection by-products, public health risk tradeoffs and me[END_REF][START_REF] Nieuwenhuijsen | Health impacts of long-term exposure to disinfection by-products in drinking water in Europe: HIWATE[END_REF][START_REF] Villanueva | Overview of Disinfection By-products and Associated Health Effects[END_REF].

Reproductive effects

Because of toxicological studies detecting adverse reproductive effects in animals, reproductive health outcomes such as low birthweight, prematurity, spontaneous abortion, congenital anomalies and stillbirth have been the focus of epidemiological studies. Studies have provided some evidence for a relationship between exposure to DBPs and small for gestational age/intrauterine growth retardation and preterm delivery. However, evidence for other outcomes such as low birthweight, stillbirth, congenital anomalies and semen quality appears to be inconclusive and inconsistent [START_REF] Hinckley | Late pregnancy exposures to disinfection byproducts and growth-related birth outcomes[END_REF][START_REF] Hrudey | Chlorination disinfection by-products, public health risk tradeoffs and me[END_REF][START_REF] Nieuwenhuijsen | Health impacts of long-term exposure to disinfection by-products in drinking water in Europe: HIWATE[END_REF][START_REF] Nieuwenhuijsen | Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review[END_REF][START_REF] Tardiff | Updated weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection byproducts[END_REF][START_REF] Villanueva | Overview of Disinfection By-products and Associated Health Effects[END_REF].

Conclusion

This paper reviewed the occurrence, origin, and toxicity of DBPs in swimming pools disinfected with chlorine. In terms of occurrence, haloamines, HAAs, THMs, HANs and HALs are the byproducts largely present in water of swimming pools treated with chlorine. Recent studies have provided evidence about the occurrence of other emerging DBP that are toxic, even at low concentrations, including nitrogenous DBPs such as N-nitrosamines, HNMs, nitramines, nitramides, and cyanogen halides as well as carbonaceous DBPs such as halobenzoquinones, haloketones, halofuranones. Although more than 100 DBPs have been identified so far [START_REF] Richardson | What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water[END_REF], we have to keep in mind that these compounds represent only a small fraction of the total organic halide (TOX) contents detected in chlorinated swimming pool waters [START_REF] Richardson | What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water[END_REF][START_REF] Freyfer | Sous-produits de chloration dans les eaux de piscine -Effet de l'ozonation[END_REF][START_REF] Manasfi | Occurrence of brominated disinfection by-products in the air and water of chlorinated seawater swimming pools[END_REF]. It is thus important to continue to investigate the nature and levels of occurrence of DBPs in pool waters so that the unknown DBPs contributing to the TOX contents could be determined. In addition, further research is required to analyse the exposure of bathers to the emerging DBPs in swimming pools and to investigate their potential health effects. Indeed, if ocular, respiratory, and cutaneous irritations seem well correlated with the presence of trichloramine and dichloromethylamine in swimming pool water, relationships between pool attendance and other adverse health effects such as asthma, different cancers, and reproductive outcomes prompt further investigations (Kogevinas et al., 2010;[START_REF] Font-Ribera | Swimming Pool Attendance, Asthma, Allergies, and Lung Function in the Avon Longitudinal Study of Parents and Children Cohort[END_REF].

The identification and quantification of DBPs in swimming pools is analytically challenging given the complexity of swimming pool water chemistry. The nature of human inputs varies considerably not only as a function of bathers' hygiene but also as a function of activities carried out in pools (relaxing, sport, therapeutic pools ...). Furthermore, pool location (indoor ou outdoor)

as well as maintenance conditions applied by pool operators, such as ventilation, rates of water renewal, adjustment of chlorine or chlorine-based disinfectant levels (depending on local regulations), and use of additives (e.g. stabilizers) can all have an impact on the occurrence of DBPs in pool water and ambient air. Moreover, the nature and levels of DBPs are clearly modified when treatments other than chlorine-based disinfection, such as ozone, ozone/chlorine, ozone/UV or UV/chlorine, are applied. Few papers compared the impact of different disinfection treatment on the toxicity of generated DBPs in swimming pools. However, the reported findings with regard to toxicity variation from one treatment to another were often conflicting (Plewa et al., 2011;[START_REF] Hansen | Optimal pH in chlorinated swimming pools -balancing formation of by-products[END_REF]Solterman et al., 2013;[START_REF] Cimetiere | Effects of UV-dechloramination of swimming pool water on the formation of disinfection by-products : a lab-scale study[END_REF][START_REF] Spiliotopoulou | Secondary formation of disinfection by-products by UV treatment of swimming ool water[END_REF].

Data presented in this review with regard to the occurrence, toxicity, and toxicological reference values of DBPs could be used in conducting risk assessment studies for swimming pools.

However, to be robust, these studies need to be correlated to daily exposure doses, and to the characteristics of people attending swimming pools (occasional swimmers, elite swimmers, baby swimmers, pregnant women, technical staff …). Volatile DBPs can be inhaled and the inhaled amounts depend on the mode of breathing, oral or nasal (Bernard et al., 2007). Swimmers can be also exposed to DBPs when water is accidently ingested. The average ingested volume varies largely as a function of swimmer categories and for the same category considerable differences have been reported in different studies (from 25 mL h -1 to 50 mL h -1 for babies, from 20 to 25 mL h -1 for swimmers, and from 170 to 225 mL h -1 for elite swimmers) [START_REF] Dufour | Water ingestion during swimming activities in a pool: a pilot study[END_REF]WHO, 200). Another route of exposure of swimmers to DBPs is through dermal absorption. Some DBPs can cross the cutaneous barrier but the limited data available make difficult determining the contribution of the dermal exposure route to the overall exposure. Biomonitoring and investigations about the pharmacokinetic profiles of DBPs would provide data that is vital to improve risk assessment studies. In addition, a better understanding of the occurrence of DBPs in swimming pools, their formation and transformation mechanisms, and their toxicity, is required so that efficient preventive measures could be taken to reduce their formation and to minimize the exposure of swimmers to these chemical contaminants.

  .,

	Country	Air (µg.m -3 ) NCl 3	NCl 3	NHCl 2 Water (µg L -1 )	NH 2 Cl		References
	France	20-1260		5-1700*		indoor	Anses, 2010; Bessonneau et al., 2011
	Switzerland	38-520		-		indoor	Parrat et al., 2012
	Québec	300-510	102-568	38-206	171-948	indoor	Simard et al., 2013; Lévesque et al., 2015
		-	2.6-280	1.3-137	4-430	outdoor	Simard et al., 2013
		80-350	<LOD-650	<LOD-593	<LOD-450	indoor	Catto et al., 2012
	USA	-	<LOD-377	<LOD-147	<LOD-1180	indoor	Weaver et al., 2009
			100-800**	80-180	180-320	indoor	Weng et al., 2011
	Taïwan	17-150	100-1650*			indoor	Chu et al., 2013
	Sweden	1-640		-		indoor	Westerlund et al., 2015
	Italy	200-1020		-		indoor	Fantuzzi et al., 2013
	Spain	170-430	<LOD-377	<LOD-650	100-640	indoor	Richardson et al., 2010
		248-858	<lod-1600	<lod-700	<lod-700	indoor	Font-Ribera et al., 2016
	*these values represent the sum of inorganic chloramines determined using the DPD method
	** these high values can be explained because of sampling during a swimming competition
	<LOD : below the limit of detection

Table 2 :

 2 Occurrence of trihalomethanes (THM) in indoor swimming pools

  Simard et al.

						Water (µg.L -1 )			Air (µg.m -3 )		References
			n	CHCl 3	CHCl 2 Br	CHClBr 2	CHBr 3	CHCl 3	CHCl 2 Br	CHClBr 2	CHBr 3
		Italy	5	6.1-68.4	2-5.3	0.4-5.4	<lod	19-58.6	2.9-13	0.3-6	<lod-0.8	Fantuzzi et al., 2001
			1	8.5-20	9.4-25	6.7-23	3.1-16	18-61	8.2-23	6.4-22	5.9-22	Lourencetti et al., 2012
			24	2.5-122	1.4-18.3	0.2-11.7	<lod-3.6					Righi et al., 2014
		Korea	30	<lod-45.8	<lod-7	<lod	<lod			-		Lee et al., 2010
	Chlorine-	Spain	1	24-61.6	3.8-12.9	0.9-4.7	0.2-1.9			-		Font-Ribera et al., 2016
	based
	disinfectant		16	22.3-217	3.6-25.2	0.4-5.3	0.2-2.8			-		Font-Ribera et al., 2010
			12	8.4-20.8	9.3-26.8	6.5-22.6	3-16.5	11.9-61.6	7.5-23.4	6.1-26.2	4.4-22.6	Richardson et al., 2010
		USA	11	<lod-173	<lod-150	<lod-54	<lod-67.9			-		Weaver et al., 2009
		Canada 41	6.7-126.5	<lod-30.1	<lod-51.3	<lod-45.6	20.3-320.4	1.3-154.6	<lod-204.8 <lod-102.8	Tardif et al., 2016
			15	12.9-215	<lod-23.9	<lod-27.1	<lod-19.2					Simard et al., 2008
		France	8	0.03 -0.3	0.05-1.1	13.6-63.6	28-930			-		Parinet et al., 2012
	Bromine-		3	<lod	<lod	1.6-3.9	48.9-62.5			-		Manasfi et al., 2016
	based
	disinfectant or		3	<lod	<lod	2.1-5.5	49.7-101.3	<lod	<lod	3.6-20.7	21.7-240.1	Manasfi et al., 2017b
	chlorinated bromide-rich	Italy	1	0.08-0.29	0.23-0.6	2.1-2.6	52-61	1.8-6.9	1.9-4.2	6.4-8.7	55-92	Lourencetti et al., 2012
	waters	Spain	4	0.5-2	0.3-2.5	1.2-5.1	78.6-146.6			-		Font-Ribera et al., 2010
			7	0.08-0.3	0.22-0.43	2.1-2.5	52-64	1.7-4.8	1.7-2.8	6.0-7.7	53-77	Marco et al., 2015
		n = number of pools analyzed	-: not determined; <lod : below the limit of detection

Table 3 :

 3 Occurrence of haloacetic acids (HAA) in swimming pools

	Nature of water	Country	n	DCAA		TCAA
		Korea	30	14.1-246		19.7-636
		Switzerland	4	0.9-240		17.1-94.7
		USA	25	67-166		93-136
		France	8	12-247		16-461
	Freshwater
		Canada	41	27.4-500		24.1-249.6	Tardif et al., 2016
		Italy	24	<lod-291		<lod-403	Righi et al., 2014
		Spain	30	15.4-51.7		39.2-83.4	Font-Ribera et al., 2016
		Australia	11	230-2400		110-2600	Yeh et al., 2014
				BCAA	DBAA	BDCAA	CDBAA	TBAA
	Bromine-disinfectant USA	6	<lod-294 90.5-1795 6.3-117 2.5-13.5	26.2-175	Daiber et al., 2016
	Seawater	France	10	3.5-216.1 11.3-1088 1.1-20.2 4-427.6	39-53.2	Parinet et al., 2012; Manasfi et al., 2016
	<lod : below the limit of detection
	DCAA : dichloroacetic acid; TCAA : trichloroacetic acid; BCAA : bromochloracetic acid; BDCAA : bromodichloroacetic acid;
	CDBAA : Chlorodibromoacetic acid; TBAA : Tribromoacetic acid
	All concentrations are expressed in µg L -1

Table S1 :

 S1 Physico-chemical properties of main DBPs found in swimming pools

Table 5 :

 5 Levels of UV filters in swimming pools detected in previous studies

			UV filter Concentrations (ng L -1 )
	Country	Type of pool	OXY (BP3)	ODPABA	4-MBC	OMC	OC	PBS	Reference
	Greece	Swimming pool	2400-3300	2100					Lambropoulou et al. (2002)
	Greece	Swimming pool	4.2		6.9	4.5			Giokas et al. (2004)
		Game pool	5.7		5.4	3.0
	Germany	Swimmer pool				1800	7000	0.7	Zwiener et al. (2007)
		Non-swimmer pool				2700	11000	2
		Baby pool	1200			7000	25000	16
	Slovenia	swimming pool	400	17	330		15		Cuderman and Heath (2007)
	Spain	Swimming pool	<LOD-2326		43-4035	107-1462	1421-25967		Negreira et al. (2010)
	Italy	Swimming pool (seawater)	25-216			53-86			Nguyen et al. (2011)
	Czech Republic Swimming pool(outdoor)	26-620					240-13000	Grabicova et al. (2013)
	Spain	Swimming pool (Indoor)	<0.1-4.87	<0.1	<0.4-5.6				Ekowati et al. (2016)
		Swimming pool (outdoor)	<0.1-15.17	<0.1-2.0	<0.4-35.9
		Children pool (indoor)	<0.1-1.77	<0.1	8.6-12.1
		Children pool (outdoor)	<0.1-1.97	<0.1	8.1-45.4
		Spa	<0.1-1.07	<0.1	<0.4-69.3
	Nakajima et al., 2009 investigated the reactions of the UV filters ODPABA and octyl-4-
	methoxycinnamate (OMC) with chlorine in aqueous solution under conditions that simulate those
	found in swimming pools. ODPABA reacted rapidly with chlorine while OMC reacted slowly
	under the same conditions. The difference in reactivity was attributed to the effect of substituents
	present on the benzene ring. Both UV filters produced monochlorinated and dichlorinated
	transformation products. The structures of the chlorinated byproducts were not identified. The
	chlorination products of OMC exhibited weak mutagenic activity on Salmonella typhimurium

TA100 strain in the Ames test.

[START_REF] Duirk | Reaction of benzophenone UV filters in the presence of aqueous chlorine: Kinetics and chloroform formation[END_REF]

studied the transformation of the two benzophenone UV filters OXY and DIOXY in the presence of excess aqueous chlorine. Both UV

Table S3 :

 S3 Toxicological Reference Values (TRV) of main DBPs International Agency for Research on Cancer; EHESP : Ecole des Hautes Etudes en Santé Publique; Afsset : Agence française de sécurité sanitaire, de l'environnement et du travail; US EPA : Unites States Environmental Protection Agency (A)[START_REF] Richardson | Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research[END_REF] Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research. Mutat.

	Compound	#CAS	Genotoxicity	IARC evaluation	Carcinogenic risk Reprotoxic risk	Treshold (yes/no)	Route of exposureCritical effect	Origin and year of the constructed TRV	TRV	Critical dose	Species
	Chloroform	67-66-3	no	2B	yes (in the animal) Yes	yes yes	inhalation ingestion	renal cell proliferation, precursor of cancer hepatotoxicity	Afsset (2008) US EPA (1998)	63 µg.m -3 0.01 mg.kg -1 -d -1	NOAEL = 5 ppm or 25 mg.m -3 male miceBDF1 LOAEL = 15 mg.kg -1 .d -1 dog
	Chlorodibromethane	124-48-1	yes (IARC)	3	no	no	yes	force-feeding	hepatotoxicity	US EPA (1991)	2.10 -2 mg.kg -1 .d -1	NOAEL = 21.4 mg.kg -1 .d -1	Rats F344 et mices B6C3F1
							no	force-feeding	carcinoma and hepatocellular adenoma	US EPA (1991)	8.42.10 -2 mg.kg -1 .d -1 LMS model	Rats F344 et mices B6C3F1
	Bromodichloromethane 75-27-4	yes (A)	2B	yes (in animals)	No	yes	force-feeding	renal citomegalia	US EPA (1987)	2.10 -2 mg.kg -1 .d -1	LOAEL = 17.9 mg.kg -1 .d -1	Rats F344 et mices B6C3F1
							no	force-feeding	Adenoma and adenocarcinoma of renal tubular cells US EPA (1987)	6.2.10 -2 mg.kg -1 .d -1 LMS model	Rats F344 et mices B6C3F1
							no	inhalation	neoplastic lesion in the large intestine	US EPA (1991)	1.10 -6 µg.m -3	LMS model	Rats F344 et mices B6C3F1
	Bromoform	75-25-2	yes (A)	3	no	yes	yes	force-feeding	liver damages	US EPA (1991)	2.10 -2 mg.kg -1 .d -1	NOAEL : 17.9 mg.kg -1 .d -1	Rats F344 et mices B6C3F1
							no	force-feeding	neoplastic lesion in the large intestine	US EPA (1991)	7.9.10 -3 mg.kg -1 .d -1 LMS model	Rats F344 et mices B6C3F1
	Trichloramine	10025-85-1					yes	inhalation	increase in serum level of SPA and SPB pneuproteins	EHESP (2009)	4.10 -3 mg.m -3	0.355 mg.m -3	Human
	Chloral hydrate	302-17-0	ambiguous	3	yes (in mice)	yes (in animals) yes	ingestion	depression of the central nervous system and gastrointestinal irritations	US EPA (2000)	0.1 mg.kg -1 .d -1	LOAEL : 10.7 mg.kg -1 .d -1	Human
							yes	ingestion	Adenoma and hepatic carcinoma	Sante canada (2008) 0.0045 mg.kg -1 .d -1	13.5 mg.kg -1 .d -1	Rats F344 et mices B6C3F1
	N-nitrosodimethylamine 62-75-9	Yes	2A	yes (in mice)	yes (in animals) no	ingestion	induction of liver tumours	US EPA (1993)	51 mg.kg -1 .d -1	Weibull method	Colwoth female rats
	Chloroacetic acid	79-11-8	No		no	yes (in animals) yes	force-feeding	change in body, kidney, liver and testis weight	Sante canada (2008) 0.0117 mg.kg -1 .d -1	13.5 mg.kg -1 .d -1	Rats
						yes (in animals) yes	ingestion	testiuclar, liver and brain lesions	US EPA (2003)	4.10 -3 mg.kg -1 .d -1	LOAEL : 12.5 mg.kg -1 .d -1	Beagle dogs
	Dichloroacetic acid	79-43-6	yes (IARC)	2B	yes		no	ingestion	liver tumour and hepatocellular carcinoma	Sante canada (2008) 1.02.10-6 mg.kg -1 .d -1 model	BCF63F1 male mices
							no	ingestion	hepatoadenoma and hepatocarcinoma	US EPA (2003)	0.015 mg.kg -1 .d -1	BMD	BCF63F1 male mices
	Trichloroacetic acid	76-03-9	no (IARC)	3	yes (in mice)	yes (in animals) yes	ingestion	change in body weight and increase in hepatic enzymSante canada (2008) 0.0325 mg.kg -1 .d -1	32.5 mg.kg -1 .d -1	Rats
	Bromoacetic acid	79-08-3	no	3	no	yes (in animals)
	Dibromoacetic acid	631-64-1	yes		no	yes (in animals) no no	ingestion ingestion	malignant mesothelioma hepatoadenoma and hepatocarcinoma	Sante canada (2008) 4.26.10 -6 mg.kg -1 .d -1 LMS model Sante canada (2008) 0.14.10 -6 mg.kg -1 .d -1 LMS model	BCF63F1 male mices BCF63F1 male mices
	Dichloroacetonitrile	3018-12-0
	Dibromoacetonitrile	3252-43-5	yes (A)	3	no
	Trichloroacetonitrile	545-06-2
	NOAEL : No Observable Adverse Effect Level; LOAEL : Lowest Observed Adverse Effect Level
	IARC : Res. 636, 178-242

Table 6 :

 6 Genotoxicity and carcinogenicity of THMs and HAAs

			Genotoxicity
		Gene mutation		Chromosomal mutation	DNA damage
	Compounds	Bacteria	Mammalian	In vitro	In vivo	In vitro	In vivo
			cells
	Bromodichloromethane	+		-		+	-
	Bromoform	+	+	+	+	+	-
	Chlorodibromomethane	+	+	+		-
	Chloroform	-	-	-	-	+
	Monochloroacetic acid	-	+			-	-
	Monobromoacetic acid	+				+
	Dibromoacetic acid	+				+
	Dichloroacetic acid	+	+	+	+	-
	Trichloroacetic acid	-	-			-	-
	Chloral hydrate*	-	-	-		-
	Bromal hydrate*	+	+	-		+
			Carcinogenicity
		Rodents		Classification in Humans
	Compounds	Mices,	Rats F344	IARC		EPA
		B6C3F1
	Bromodichloromethane	+, -, -	+, -, -	2B		B2
	Bromoform	-	+	3		B2
	Chlorodibromomethane	+	-	3		C
	Chloroform	+, -	+, +, +	2B
	Monochloroacetic acid	-	-, -
	Monobromoacetic acid
	Dibromoacetic acid	+	+
	Dichloroacetic acid	+	+	2B		B2
	Trichloroacetic acid	+	-	3		C
	All references come from the ANSES' review, except for compounds marked with *, coming from Manasfi et al., 2017a