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Diss Factsheets

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1990
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: abstract only; information not sufficient for an assessment

Data source

Reference
Reference Type:
publication
Title:
Comparative analysis of the uptake and distribution of inhaled, 14C-labeled isocyanates in blood
Author:
Kennedy AL, Alarie Y and Brown WE
Year:
1990
Bibliographic source:
Toxicologist 40, p 236

Materials and methods

Objective of study:
metabolism

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexamethylene diisocyanate
EC Number:
212-485-8
EC Name:
Hexamethylene diisocyanate
Cas Number:
822-06-0
Molecular formula:
C8H12N2O2
IUPAC Name:
1,6-diisocyanatohexane
Constituent 2
Reference substance name:
toluene diisocyanate
IUPAC Name:
toluene diisocyanate
Constituent 3
Chemical structure
Reference substance name:
Methyl isocyanate
EC Number:
210-866-3
EC Name:
Methyl isocyanate
Cas Number:
624-83-9
Molecular formula:
C2H3NO
IUPAC Name:
isocyanatomethane
Details on test material:
Hexamethylene diisocyanate, toluene diisocyanate, methyl isocyanate (analogy)
Radiolabelling:
yes

Test animals

Species:
guinea pig

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
unchanged (no vehicle)
Details on study design:
A comparative analysis of the uptake and distribution of inhaled,  14C-labelled isocyanates was performed by exposure of guinea pigs to  vapour concentrations at or above the respective TLV for 1 h. 

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Uptake in  the blood was immediate, dose-dependent and increased linearly to a 2 -4 h  postexposure peak.  The authors conclude that the uptake is independent  of the chemical structure of the isocyanate.
Details on excretion:
Clearing of radioactivity from the blood was rapid; a  nanomolar level persisted after 72 h, regardless of the initial dose, in  protein-bound form.

Applicant's summary and conclusion

Conclusions:
A comparative analysis of the uptake and distribution of inhaled,  14C-labelled isocyanates was performed by exposure of guinea pigs to  vapour concentrations at or above the respective TLV for 1 h.  Uptake in  the blood was immediate, dose-dependent and increased linearly to a 2 -4 h  postexposure peak.  The authors conclude that the uptake is independent  of the chemical structure of the isocyanate. Clearing of radioactivity from the blood was rapid; a  nanomolar level persisted after 72 h, regardless of the initial dose, in  protein-bound form.
Executive summary:

A comparative analysis of the uptake and distribution of inhaled, 14C-labelled isocyanates was performed by exposure of guinea pigs to  vapour concentrations at or above the respective TLV for 1 h.  Uptake in  the blood was immediate, dose-dependent and increased linearly to a 2 -4 h  postexposure peak.  The authors conclude that the uptake is independent  of the chemical structure of the isocyanate. Clearing of radioactivity from the blood was rapid; a  nanomolar level persisted after 72 h, regardless of the initial dose, in  protein-bound form.