Hexane, 1,6-diisocyanato-2,2,4(or 2,4,4)-trimethyl-

Basic toxicokinetics

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

Test material information

Constituent 1

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

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.