Toxicokinetic Study of Lambda-cyhalothrin Biomarkers of Exposure

May 17, 2017 updated by: Michèle Bouchard, Université de Montréal

La Lambda-cyhalothrine Comme Insecticide privilégié en Milieu Agricole: étude de la toxicocinétique de Biomarqueurs Pour le Suivi de l'Exposition Des Travailleurs

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 64 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicokinetic parameters of lambda-cyhalothrin elimination after oral and dermal exposure.
Time Frame: 84-h post-treatment
Elimination half-lives of biomarkers of exposure
84-h post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Université de Montréal

Investigators

  • Principal Investigator: Michèle Bouchard, PhD, Université de Montréal
  • Principal Investigator: Jonathan Côté, MSc, Université de Montréal
  • Principal Investigator: Rania Khemiri, BSc, Université de Montréal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 22, 2016

Primary Completion (Actual)

November 19, 2016

Study Completion (Actual)

April 30, 2017

Study Registration Dates

First Submitted

May 15, 2017

First Submitted That Met QC Criteria

May 16, 2017

First Posted (Actual)

May 18, 2017

Study Record Updates

Last Update Posted (Actual)

May 19, 2017

Last Update Submitted That Met QC Criteria

May 17, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • IRSST-2010-0009

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Exposure to Pollution

Clinical Trials on Exposure

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bahamas

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe