Toxicokinetic Study of Dichlorobisphenol A After an Oral or Dermal Single Dose in Healthy Volunteer.

Study Overview
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Brief Summary
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The objective of this study is to determine toxicokinetic parameters of deuterated d12-Cl2BPA after the administration of a single low dose (50 µg/kg) to healthy volunteers via oral or dermal routes.

Detailed Description
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Dichlorobisphenol A (Cl2BPA)is formed by the reaction of chlorine with bisphenol A present in water during water disinfection process. As a consequence, Cl2BPA is present in various aqueous media including tap water. Cl2BPA has also been found in human, in blood, urine, breast milk and adipose tissue suggesting chronic exposure to this compound. Cl2BPA is an endocrine disruptor that binds to estrogenic and PPAR-γ receptors. Epidemiological studies have shown that exposure to DCBPA has been related to the occurrence of diabetes, obesity and myocardial infarction. Currently, no toxicokinetic data are available to estimate the disposition (ADME) of Cl2BPA after oral and dermal exposure in human while these data are needed for proper risk assessment of this compound. The objective of this study is to determine toxicokinetic parameters of deuterated d12-Cl2BPA after the administration of a single low dose (50 µg/kg) to healthy volunteers via oral or dermal routes.

Official Title
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Toxicokinetic Study of Dichlorobisphenol A After an Oral or Dermal Single Dose in Healthy Volunteer.

Conditions
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Pharmacokinetic Study

Intervention / Treatment
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* Other: Administration of d12-Cl2BPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-51 year old No current disease BMI range: 18.5-24.9 kg/m², Non smoker Normal renal function Normal hepatic function Normal gastrointestinal function Affiliated to national health insurance Having signed an informed consent Exclusion Criteria: Renal function ≤ 90 ml/min/1.73 m² (CKD-EPI) Altered hepatic function ASAT > 50 UI/L and/or ALAT > 50 UI/L, Current disease, Heavy alcohol consumption No treatment susceptible to alter Cl2BPA toxicokinetics (drugs that interact with metabolic enzymes or transporter proteins,, anti-acids, etc) Pregnant women, lactating mothers and women of childbearing potential with no reliable medical contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 51 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Oral route = 6 volunteers Dermal route = 6 volunteers
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral route<br>Volunteers receiving d12-Cl2BPA via oral route | Other: Administration of d12-Cl2BPA<br>* Administration of d12-Cl2BPA<br>|
| Experimental: Dermal route<br>Volunteers receiving d12-Cl2BPA via oral route | Other: Administration of d12-Cl2BPA<br>* Administration of d12-Cl2BPA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | Non-compartmental and compartmental toxicokinetic analysis | Hour 0-Hour 24 | 
| Cmax | Non-compartmental and compartmental toxicokinetic analysis | Hour 0-Hour 24 | 
| Total clearance | Non-compartmental and compartmental toxicokinetic analysis | Hour 0 - Hour 24 | 
| Volume of distribution | Non-compartmental and compartmental toxicokinetic analysis | Hour 0 - Hour 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary toxicokinetic parameters | half-life | Hour 0 - Hour 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Toxicokinetics, Endocrine Disruptors, Bisphenol A derivatives