Impact of Thermal Stress on Pulmonary Absorption and Toxicokinetics of 3 Organic Solvents

Studying the Impact of Thermal Stress (Heat) Representative of Occupational Settings on Pulmonary Absorption and Toxicokinetics of 3 Organic Solvents

In Quebec, thousands of workers are concomitantly exposed to heat and chemical compounds. Exposure to heat induces physiological responses that help maintaining a stable body temperature. Those changes can affect organ functions implicated in absorption and metabolism. According to literature, those changes could lead to increased concentrations of chemical compounds in the body and their toxicity. Therefore, the aim of this study is to evaluate the pulmonary absorption and toxicokinetics of 3 organic solvents in heat stress conditions in volunteers exposed in a inhalation chamber. Results will then be used to develop PBPK models that will allow to predict organic solvent kinetics when coexposed with heat.

Study Overview

• Status: Unknown
• Conditions: Heat
• Intervention / Treatment: Other: Heat stress (21); Other: Heat stress (25); Other: Heat stress (30); Other: Heat Stress (21) +TOL; Other: Heat stress (25) + TOL; Other: Heat stress (21) + TOL; Other: Heat stress (21) + ACE; Other: Heat stress (25) + ACE; Other: Heat stress (30) + ACE; Other: Heat stress (21) + DCM; Other: Heat stress (25) + DCM; Other: Heat stress (30) + DCM; Other: Heat stress (21) + TOL (dermal); Other: Heat stress (25) + TOL (dermal); Other: Heat stress (30) + TOL (dermal)

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1J4
      • Recruiting
      • Université de Montréal
      • Contact: Sami Haddad, Ph.D; Phone Number: 36188 514-343-6111; Email: sami.haddad@umontreal.ca
      • Principal Investigator: Sami Haddad, PhD
      • Sub-Investigator: Axelle Marchand, M.Sc
      • Sub-Investigator: Pierre Brochu, PhD
      • Sub-Investigator: Ginette Truchon, PhD
      • Sub-Investigator: Jessie Ménard, M.Sc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body mass index between 18,5 et 25 kg/m3

Exclusion Criteria:

• Smoking
• Respiratory, cardiovascular and neurological problems
• History of exposure to solvents
• Chronic medication
• Abusive and/or chronic alcohol consumption
• Alcohol consumption 24h before or 18h following exposure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Heat stress; 4h exposure to heat stress alone or in combination with different solvents. Solvent concentrations are equal to their TLV. Heat conditions are 21, 25 and 30°C (WBGT). Inhalation exposure for all solvents and demal exposure for toluene.

Other: Heat stress (21); 4h exposure to heat (WBGT of 21°C), no solvent; Other: Heat stress (25); 4h exposure to heat (WBGT of 25°C), no solvent; Other: Heat stress (30); 4h exposure to heat (WBGT of 30°C), no solvent; Other: Heat Stress (21) +TOL; 4h exposure to heat (WBGT of 21°C) + Toluene (concentration = TLV); Other: Heat stress (25) + TOL; 4h exposure to heat (WBGT of 25°C) + Toluene (concentration = TLV); Other: Heat stress (21) + TOL; 4h exposure to heat (WBGT of 30°C) + Toluene (concentration = TLV); Other: Heat stress (21) + ACE; 4h exposure to heat (WBGT of 21°C) + Acetone (concentration = TLV); Other: Heat stress (25) + ACE; 4h exposure to heat (WBGT of 25°C) + Acetone (concentration = TLV); Other: Heat stress (30) + ACE; 4h exposure to heat (WBGT of 30°C) + Acetone (concentration = TLV); Other: Heat stress (21) + DCM; 4h exposure to heat (WBGT of 21°C) + Dichloromethane (concentration = TLV); Other: Heat stress (25) + DCM; 4h exposure to heat (WBGT of 25°C) + Dichloromethane (concentration = TLV); Other: Heat stress (30) + DCM; 4h exposure to heat (WBGT of 30°C) + Dichloromethane (concentration = TLV); Other: Heat stress (21) + TOL (dermal); 4h exposure to heat (WBGT of 21°C) + Toluene (concentration = TLV), participants breath normal air through a mask for evaluation of dermal absorption.; Other: Heat stress (25) + TOL (dermal); 4h exposure to heat (WBGT of 25°C) + Toluene (concentration = TLV), participants breath normal air through a mask for evaluation of dermal absorption.; Other: Heat stress (30) + TOL (dermal); 4h exposure to heat (WBGT of 30°C) + Toluene (concentration = TLV), participants breath normal air through a mask for evaluation of dermal absorption.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory rate	Respiratory rate will be monitored continuously for 4hour with a respirometer	4hour
Cardiac frequency	Cardiac frequency will be monitored continuously for 4hour with a respirometer	4hour
Minute ventilation	Minute ventilation will be monitored continuously for 4hour with a respirometer	4hour
Tidal volume	Tidal volume will be monitored continuously for 4hour with a respirometer	4hour
Solvent in blood	Solvents concentrations will be measured in blood samples collected at different times (t=0, 2, 4 and 4.5hour).	4,5hour
Solvent or metabolite in urine	Solvent or metabolite concentrations (o-cresol for toluene exposures) will be measured for urine samples collected at different times (t=0, 4, 10 and 18hour).	18hour
Solvent in exhaled air	Solvents concentrations will be measured in exhaled air samples collected at different times (t=0, 1.5, 3, 4.5 and 6hour).	6hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen consumption	oxygen consumption will be monitored continuously for 4hour with a respirometer	4hour
Carbonic dioxide production	carbonic dioxide production will be monitored continuously for 4hour with a respirometer	4hour
Body temperature	Body temperature is monitored continuously by telemetry	4hour

Collaborators and Investigators

• Sponsor: Université de Montréal
• Collaborators: Institut de Recherche Robert-Sauvé en Santé et en Sécurité du Travail
• Investigators: Study Director: Sami Haddad, Ph.D, Université de Montréal

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: January 15, 2016
• First Submitted That Met QC Criteria: January 19, 2016
• First Posted (Estimate): January 20, 2016

Study Record Updates

• Last Update Posted (Estimate): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 19, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Physiologically based pharmacokinetic modeling; Organic solvents
• Other Study ID Numbers: 14-140-CERES-P; 2013-0012 (IRSST)