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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
7

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Université de Montréal

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 22, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 19, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 15, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 18, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 19, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

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