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Toxicokinetic Study of Lambda-cyhalothrin Biomarkers of Exposure

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ClinicalTrials.gov Identifier: NCT03159013
Recruitment Status : Completed
First Posted : May 18, 2017
Last Update Posted : May 19, 2017
Sponsor:
Information provided by (Responsible Party):
Michèle Bouchard, Université de Montréal

Brief Summary:
Exposure to pyrethroid pesticides is a growing concern in the workplace especially since they are also present in the diet of the general population. It is important to monitor human exposure to these contaminants. Exposure to pyrethroids may occur by multiple routes of exposure (oral, inhalation and dermal), such that it is difficult to assess absorbed doses from external exposure assessments. Biological monitoring, which consists of measuring urinary metabolites, is now recognized by the scientific community as a preferred approach to assess exposure to this type of compound. These metabolites are biotransformation products produced in the human body from the exposure compounds. However, interpretation of these biological monitoring data requires a proper knowledge of the kinetic behavior and thus the fate of the substance of interest in the human body in order to link levels of biomarkers in individuals to actual absorbed doses. Human kinetic data are still poorly documented in the case of pyrethroids. The study in volunteers exposed to pyrethroids in controlled conditions will allow acquiring new urinary and blood profiles to refine and address uncertainties in the toxicokinetics of lambda-cyhalothrin following oral and dermal exposure. Those data will serve to build a toxicokinetic model to predict absorbed doses in workers from urinary metabolite measurements and therefore better assess health risks.

Condition or disease Intervention/treatment Phase
Exposure to Pollution Other: Exposure Not Applicable

Detailed Description:

Lambda-cyhalothrin is a synthetic pyrethroid pesticide widely used in Quebec to fight against pests in vegetable crops. In recent years, this pyrethroid has become one of the most used insecticides in these crops. However, there is a paucity of data on the biological behavior of this molecule in humans. Given the extensive use of this pyrethroid, it becomes essential to develop tools to properly assess exposure among workers largely in contact with pesticides during spraying or work in treated areas. Biological monitoring, which consists of measuring urinary metabolites is considered a preferred approach to evaluate absorbed doses of this type of product in the workplace, given the potentially combined exposure through the respiratory, dermal and oral routes. However, interpretation of biological monitoring data requires a good knowledge of the kinetic behavior of the substance of interest in the human body, to link biomarker levels among workers to actual absorbed doses. The overall objective of this project is to address the lack of knowledge on the toxicokinetics of biomarkers of exposure to lambda-cyhalothrin in humans for a better interpretation of routine biomonitoring data and hence health risks in exposed workers. First, a controlled kinetic study will be conducted in volunteers exposed acutely to a low oral dose of lambda-cyhalothrin (oral reference dose) followed by a cutaneous dose (of lambda-cyhalothrin formulation used by sprayers). The protocol will be similar to a previous one used by our team for toxicokinetic assessment of other pesticides. Secondly, a toxicokinetic model will be developed to simulate the kinetics of biomarkers of exposure to lambda-cyhalothrin, using data from the controlled kinetic study and based on a previous toxicokinetic model for related pyrethroids.

More specifically, volunteers will be exposed orally to 0.025 mg/kg body weight of lambda-cyhalothrin (single oral dosing). According to recent health risk assessment by the US Environmental Protection Agency (US EPA), volunteers should not incur any adverse effects relating to such dosing. Three weeks following oral dosing (to allow complete elimination of the compound from the body), the same volunteers will be exposed dermally to a lambda-cyhalothrin-based formulation used on crops. The formulation will be applied on a 40cm2 surface of the forearm at a concentration corresponding to the one used in the workplace (Matador 120EC). The treated area will not be washed for a period of 6 h. This type of application will be similar to that of exposed workers. Urinary and blood measurements of specific biomarkers of exposure to these insecticides will be performed. These biomarkers of exposure are already known from other studies and have been shown to be good bioindicators of exposure to pyrethroids. The kinetic profile will serve to link absorbed doses to blood and urinary concentrations of metabolites through time. Personal information on health status, diet and lifestyle will be documented. A total of 7 volunteers will spend a full day at the University during which they will be exposed to a low dose of pesticide. Blood and urinary samples will be collected. Four short visits of one hour will be needed for blood collections. Every urine void for a period of 84 hours will be collected in a different bottle. This whole process will be repeated twice to test two routes of exposure to this insecticide, oral (swallowed) and dermal (applied to the forearm).

The study in volunteers exposed to lambda-cyhalothrin in controlled conditions will allow acquiring new urinary and blood metabolite profiles to better understand their kinetic behavior and essential biological determinants of the observed profiles. These data can then be used in a toxicokinetic model to predict the main routes of exposure and associated absorbed doses in workers exposed to formulations containing lambda-cyhalothrin.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: La Lambda-cyhalothrine Comme Insecticide privilégié en Milieu Agricole: étude de la toxicocinétique de Biomarqueurs Pour le Suivi de l'Exposition Des Travailleurs
Actual Study Start Date : September 22, 2016
Actual Primary Completion Date : November 19, 2016
Actual Study Completion Date : April 30, 2017

Arm Intervention/treatment
Pesticide toxicokinetics- oral
Exposure type: ORAL Toxicokinetics
Other: Exposure

Oral exposure: 0,025 mg/kg bw dissolved in oil, on day 1, with blood withdrawn on days 2,3,4.

Dermal exposure: 145 µl of commercial formulation (0,25 mg/kg bw) on 40 cm2 of forearm skin for 6 hours, on day 28, with blood withdrawn on days 29,30,31.


Pesticide toxicokinetics- dermal
Exposure type: DERMAL Toxicokinetics
Other: Exposure

Oral exposure: 0,025 mg/kg bw dissolved in oil, on day 1, with blood withdrawn on days 2,3,4.

Dermal exposure: 145 µl of commercial formulation (0,25 mg/kg bw) on 40 cm2 of forearm skin for 6 hours, on day 28, with blood withdrawn on days 29,30,31.





Primary Outcome Measures :
  1. Toxicokinetic parameters of lambda-cyhalothrin elimination after oral and dermal exposure. [ Time Frame: 84-h post-treatment ]
    Elimination half-lives of biomarkers of exposure



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Good health
  • Caucasian origin (same group to have less genetic variability)

Exclusion Criteria:

  • Pyrethroid exposure at work or home (pet, garden)
  • Any kidney or liver illness

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03159013


Sponsors and Collaborators
Université de Montréal
Investigators
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Principal Investigator: Michèle Bouchard, PhD Université de Montréal
Principal Investigator: Jonathan Côté, MSc Université de Montréal
Principal Investigator: Rania Khemiri, BSc Université de Montréal

Additional Information:
Publications:
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Responsible Party: Michèle Bouchard, Professor, Université de Montréal
ClinicalTrials.gov Identifier: NCT03159013     History of Changes
Other Study ID Numbers: IRSST-2010-0009
First Posted: May 18, 2017    Key Record Dates
Last Update Posted: May 19, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michèle Bouchard, Université de Montréal:
Pyrethroids
Lambda-cyhalothrin
Biomarkers
Toxicokinetics