Linéarité de l’élimination sanguine de la chlordécone

PARTIE 1:Cinétiques sanguines, urinaires et fécales après administration

de chlordécone ou de chlordécol

1. Linéarité de l’élimination sanguine de la chlordécone

Un des objectifs du protocole 1 était de déterminer l’effet de la dose administrée de CLD sur l’élimina-tion chez la brebis. Les résultats de cette étude sont présentés à l’aide du manuscrit de l’article intitulé « Linear Toxicokinetic of chlordecone in ewe’s serum » et soumis dans la revue Chemosphere.

2

Maïlie Saint-Hilaire1, Guido Rychen1, Jean-Pierre Thomé2, Célia Joaquim-Justo2, Yves Le Roux1, 3

Cyril Feidt1, Agnès Fournier1*

4

Mailie.saint-hilaire@univ-lorraine.fr; guido.rychen@univ-lorraine.fr; jp.thome@ulg.ac.be; 5

celia.joacquim-gusto@ulg.ac.be; yves.leroux@univ-lorraine.fr; cyril.feidt@univ-lorraine.fr; 6 agnes.fournier@univ-lorraine.fr 7 8 9 10

1 Université de Lorraine, INRA, USC 340, UR AFPA, 2 avenue de la Forêt de Haye, TSA 40602, 11

54518, Vandœuvre-lès-Nancy Cedex, France 12

13

2 Université de Liège, LEAE-CART, Allée du 6 Août, 11, 4000, Liège, Belgium 14

15 16 17 18

*Corresponding author: Agnès Fournier 19

E-mail address: agnes.fournier@univ-lorraine.fr 20 21 Tél: 03 72 74 41 60 22 23 24 25 26 27 28 29 30 31 32

34

Chlordecone (CLD) is an organochlorine pesticide used in banana fields of the French West Indies 35

between 1972 and 1993. This use resulted in a long-term pollution of soils and the possible 36

contamination of farm animals. Indeed, after involuntary ingestion of soil, CLD is absorbed and 37

consequently leads to contaminated animals. The aim of this study was the determination of CLD half-38

life and the establishment of the linearity of CLD disappearance kinetics in non-lactating adult’s ewes. 39

CLD diluted in cremophor was intravenously administrated to ewes at different doses: 0.04; 0.2 or 1 40

mg kg-1 body weight (n=5 for each dose). Blood samples were collected from time t = 0 to time t = 84 41

days. Serum samples were extracted with a solid-phase extraction and analyzed by electron capture 42

detection gas chromatography. A two-compartmental model was applied to the serum CLD kinetics. An 43

additional statistical analysis was applied to the observed elimination parameters in serum according to 44

the administrated dose and no significant differences were detected. The linear elimination of CLD 45

between 0.04 and 1 mg kg-1 body weight allowed the possibility of ewe’s extrapolation half-life in this 46

dose range. The estimated mean CLD half-life in ewes was 24 days. Overall, the results of this study 47

will be useful to establish decontamination strategies in small ruminants reared in contaminated CLD 48

areas. 49

50

Keywords: Ewe, Chlordecone, serum, linearity, elimination, half-life 51 52 Highlights 53 54 55

• Chlordecone elimination is linear between 0.04 and 1 mg kg-1 body weight in serum 56

• The serum half-life of chlordecone is 24 ± 1 days in adult non-lactating ewe 57

• The obtained results will be useful to establish decontamination strategies in ewes 58 59 60 61 62 63

Chlordecone (CLD) is an organochlorine pesticide considered as a Persistent Organic Pollutant (POPs) 67

(UNEP 2006) formerly used from 1972 to 1993 in the French West Indies (FWI) (Le Déaut and 68

Procaccia 2009). Because of its persistence in soils (Cabidoche et al. 2009), CLD can be accumulated 69

in food chain and consequently lead to a possible exposure of the local population (Kannari 2017). CLD 70

is a carcinogenic, mutagenic and reprotoxic molecule (Multigner et al. 2010; Dallaire et al. 2012). In 71

order to limit the exposure of the local population, it is important to manage this CLD contamination 72

(Kannari 2017). CLD residues in animal products is one contributor of the local population exposure to 73

CLD. In fact, based on surveys and monitoring programs in Martinique realized by Dubuisson et al. 74

(2007), without considering water, 18.7% of contaminated meat samples contained residues of CLD. 75

Moreover, in 2011, the CLD concentrations in peri-renal adipose tissues of 12% of slaughtered bovines 76

reared in contaminated areas were found to be higher than the expected Maximum Residue Limit 77

(MRL). The MRL is set up at 100 µg CLD kg-1 of fresh matter (UE n°212/2013) and ensure the safety 78

of consumers. When the CLD concentration in animal products are higher than the MRL, the carcass 79

has to be destroyed and this fact leads to an important loss for local farmers. Because, ruminants 80

represent an important part of the food consumption (Agreste - Statistique Agricole Annuelle 2017) it 81

is important to produce safe animal products with CLD concentrations lower than the MRL. This would 82

allow to ensure the food safety of animal products and the livestock sustainably. 83

The research project INnovative Strategies to establish Safe livestock rearing systems In 84

Chlordecone Contaminated Areas (INSSICCA) aims at proposing solutions that would enable 85

maintenance of local animal production and production of safe animal products. One strategy proposed 86

in this project is the decontamination of ruminants before slaughtering. In fact, to produce safe animal 87

products, it would be possible thanks to a blood sampling and the CLD serum half-life in the animal, to 88

estimate a decontamination period allowing to obtain CLD concentrations in animal products lower than 89

the MRL. Consequently, this strategy would avoid destroying animal carcasses and in the same time 90

would reduce the local population exposure to CLD. To set up this strategy, toxicokinetics informations 91

are required about the fate of the molecule in the animal. The major way of CLD ruminants 92

2017). The persistence of CLD differs between soil types (Cabidoche et al. 2009) and concentrations 94

lower than 0.005 or higher than 1 mg kg-1 of dry matter (DM) can be found (Rochette et al. 2017). In 95

consequence, depending on the areas where the animals are reared and the rearing practices (Jurjanz et 96

al. 2017), the exposure to CLD may vary between animals and could affect the elimination time of the 97

molecule: we don’t know if the CLD half-life is depending of the dose ingested by the animal. In 98

consequence, to assess the decontamination strategy, it is necessary to evaluate the impact of the 99

ingested dose on kinetics parameters. 100

The aim of this study was to determine the toxicokinetics parameters for CLD in ewes at different 101

administrated doses. This dose comparison will allow checking the linearity of the response in serum. 102

Ewe was chosen because there is actually no data about the CLD toxicokinetics in this species and 103

because ewe is consumed by the local population (Agreste - Statistique Agricole Annuelle 2017). 104

This study is an important step for the establishment of the decontamination strategy proposed in the 105

INSSICCA research project. 106

107