NCT02659410

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
5

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Nov 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2015

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

January 15, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

January 20, 2016

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed
Last Updated

January 20, 2016

Status Verified

January 1, 2016

Enrollment Period

9 months

First QC Date

January 15, 2016

Last Update Submit

January 19, 2016

Conditions

Heat

Keywords

Physiologically based pharmacokinetic modelingOrganic solvents

Outcome Measures

Primary Outcomes (7)

  • 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 Outcomes (3)

  • Oxygen consumption

    4hour

  • Carbonic dioxide production

    4hour

  • Body temperature

    4hour

Study Arms (1)

Heat stress

EXPERIMENTAL

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)Other: Heat stress (25)Other: Heat stress (30)Other: Heat Stress (21) +TOLOther: Heat stress (25) + TOLOther: Heat stress (21) + TOLOther: Heat stress (21) + ACEOther: Heat stress (25) + ACEOther: Heat stress (30) + ACEOther: Heat stress (21) + DCMOther: Heat stress (25) + DCMOther: Heat stress (30) + DCMOther: Heat stress (21) + TOL (dermal)Other: Heat stress (25) + TOL (dermal)Other: Heat stress (30) + TOL (dermal)

Interventions

Heat stress (21)OTHER

4h exposure to heat (WBGT of 21°C), no solvent

Heat stress
Heat stress (25)OTHER

4h exposure to heat (WBGT of 25°C), no solvent

Heat stress
Heat stress (30)OTHER

4h exposure to heat (WBGT of 30°C), no solvent

Heat stress
Heat stress (21) + TOLOTHER

4h exposure to heat (WBGT of 30°C) + Toluene (concentration = TLV)

Heat stress
Heat stress (25) + TOLOTHER

4h exposure to heat (WBGT of 25°C) + Toluene (concentration = TLV)

Heat stress
Heat stress (21) + ACEOTHER

4h exposure to heat (WBGT of 21°C) + Acetone (concentration = TLV)

Heat stress
Heat stress (25) + ACEOTHER

4h exposure to heat (WBGT of 25°C) + Acetone (concentration = TLV)

Heat stress
Heat stress (30) + ACEOTHER

4h exposure to heat (WBGT of 30°C) + Acetone (concentration = TLV)

Heat stress
Heat stress (21) + DCMOTHER

4h exposure to heat (WBGT of 21°C) + Dichloromethane (concentration = TLV)

Heat stress
Heat stress (25) + DCMOTHER

4h exposure to heat (WBGT of 25°C) + Dichloromethane (concentration = TLV)

Heat stress
Heat stress (30) + DCMOTHER

4h exposure to heat (WBGT of 30°C) + Dichloromethane (concentration = TLV)

Heat stress
Heat stress (21) + TOL (dermal)OTHER

4h exposure to heat (WBGT of 21°C) + Toluene (concentration = TLV), participants breath normal air through a mask for evaluation of dermal absorption.

Heat stress
Heat stress (25) + TOL (dermal)OTHER

4h exposure to heat (WBGT of 25°C) + Toluene (concentration = TLV), participants breath normal air through a mask for evaluation of dermal absorption.

Heat stress
Heat stress (30) + TOL (dermal)OTHER

4h exposure to heat (WBGT of 30°C) + Toluene (concentration = TLV), participants breath normal air through a mask for evaluation of dermal absorption.

Heat stress

Eligibility Criteria

Age18 Years - 50 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Université de Montréal

Montreal, Quebec, H3T 1J4, Canada

RECRUITING

Related Publications (1)

  • Marchand A, Menard J, Brochu P, Haddad S. Modeling the impact of heat stress on the toxicokinetics of toluene and acetone. Arch Toxicol. 2024 Feb;98(2):471-479. doi: 10.1007/s00204-023-03646-6. Epub 2023 Dec 21.

    PMID: 38127129DERIVED

MeSH Terms

Interventions

Heat-Shock Response3',5'-dichloromethotrexateAdministration, Cutaneous

Intervention Hierarchy (Ancestors)

Stress, PhysiologicalPhysiological PhenomenaAdministration, TopicalDrug Administration RoutesDrug TherapyTherapeutics

Study Officials

  • Sami Haddad, Ph.D

    Université de Montréal

    STUDY DIRECTOR

Central Study Contacts

Sami Haddad, Ph.D

CONTACT

514-343-6111sami.haddad@umontreal.ca

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

January 15, 2016

First Posted

January 20, 2016

Study Start

November 1, 2015

Primary Completion

August 1, 2016

Study Completion

June 1, 2018

Last Updated

January 20, 2016

Record last verified: 2016-01

Locations

CA(1)