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

Not Applicable

• Conditions: Heat
• Interventions: 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)

• Registration Number: NCT02659410
• Lead Sponsor: Université de Montréal

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11
• Status Verified: 2016-01
• Study First Submitted: 2016-01-15
• Study First Submitted QC: 2016-01-19
• Last Update Submitted: 2016-01-19
• Study First Posted: 2016-01-20
• Last Update Posted: 2016-01-20
• Primary Completion: 2016-08
• Study Completion: 2018-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 5

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Heat stress	Heat stress (21) + TOL	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.
Heat stress	Heat stress (21) + ACE	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.
Heat stress	Heat stress (21)	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.
Heat stress	Heat stress (25)	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.
Heat stress	Heat stress (30)	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.
Heat stress	Heat Stress (21) +TOL	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.
Heat stress	Heat stress (25) + TOL	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.
Heat stress	Heat stress (25) + ACE	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.
Heat stress	Heat stress (25) + TOL (dermal)	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.
Heat stress	Heat stress (30) + ACE	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.
Heat stress	Heat stress (30) + TOL (dermal)	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.
Heat stress	Heat stress (21) + DCM	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.
Heat stress	Heat stress (25) + DCM	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.
Heat stress	Heat stress (30) + DCM	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.
Heat stress	Heat stress (21) + TOL (dermal)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Body temperature	4hour	Body temperature is monitored continuously by telemetry
Oxygen consumption	4hour	oxygen consumption will be monitored continuously for 4hour with a respirometer
Carbonic dioxide production	4hour	carbonic dioxide production will be monitored continuously for 4hour with a respirometer

Trial Locations

Locations (1)

Université de Montréal; 🇨🇦 Montreal, Quebec, Canada