TDI Biuret

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1997

Materials and methods

Type of study / information:

in vivo, biomonitoring / identification of biomarkers

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Blood and urine samples were collected from six workers and two volunteers exposed to thermal degradation products from TDI-based polyurethane before and during the summer vacation. Air samples were collected on filters impregnated with 9-(N-methylaminomethyl)anthracene (MAMA) and the concentration of the amines corresponding to 2,4- and 2,6-TDA were determined in urine (U-TDA), plasma (P-TDA) and erythrocytes (E-TDA) after acid hydrolysis as pentafluoropropionic anhydride derivates by GC-MS.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

m-tolylidene diisocyanate

EC Number:

247-722-4

EC Name:

m-tolylidene diisocyanate

Cas Number:

26471-62-5

IUPAC Name:

2,4-diisocyanato-1-methylbenzene

Method

Details on study design:

- Six workers and two volunteers participated in this study. The work took place in a flame lamination factory applying a thin layer of TDI-based flexible foam on to textile fabric. The work took place from 7:00 am to 4:00 pm. Four workers were involved in the lamination process and two workers in cutting the laminated fabric. The volunteers were mainly involved in collecting air samples.
- no information regarding age, health or sex of the workers is available

Details on exposure:

Doses/Concentrations:
Worker A: 3.5 and 10 µg/m3
Worker B: 0.9 and 2.6 µg/m3
Worker C: 1.8 and 6.5 µg/m3
Worker D: 1.4 and 4.7 µg/m3
Worker E: 1.6 and 4.1 µg/m3
Worker F: 2.1 and 7.4 µg/m3
Volunteers: not determined

Results and discussion

Results:

Excretion: During work U-TDA was rapidly eliminated and a slower elimination phase was seen during exposure-free period. (In 2 workers one sample was considerably above the ideal elimination curve. In those cases unnoticed TDA exposure was assumed).

Half-life 1st: 18 d for 2,4-TDA in workers (Mean, slow phase)
Half-life 1st: 19 d for 2,6-TDA in workers (Mean, slow phase)
Half-life 1st: 5.3 and 6.2 h for the two volunteers for 2,4-TDA
Half-life 1st: 8.4 and 7.4 h for the two volunteers for 2,6-TDA

Any other information on results incl. tables

BIOMARKERS IN HYDROLYSED URINE

During the work U-TDA was rapidly eliminated and a slower elimination phase was seen during the exposure-free period. The medians of the urinary half-lives were for the slow phase 15d for 2,4-TDA and 19d for 2,6-TDA (5.8 and 7.9 for the two volunteers).

BIOMARKERS IN HYDROLYSED PLASMA AND ERYTHROCYTES

The concentration of 2,4-TDA in plasma was in the range 2.5 - 19 ng/ml and those for 2,6-TDA in the range 4.4 - 30 ng/ml among workers. In erythrocytes the concentration of 2,4-TDA was in the range of 0.5 - 6.6 ng/g and those of 2,6-TDA in the range 1.2 - 14 ng/g among workers. Significant linear relationships were seen between the mean concentrations, for all individual samples, in plasma and erythrocytes of 2,4-TDA and 2,6-TDA. P-TDA declined slowly after work cessation. The half-lives in plasma were in the range 6.5 - 12 d for 2,4-TDA and 7 -11 d for 2,6-TDA. E-TDA declined too little for the calculation of half-lives. When the mean daily urinary concentrations were adjusted for creatine there were correlations with P-TDA and E-TDA (except for E-2,4 -TDA). There was a significant correlation between P-TDA and E-TDA (except for E-2,6 -TDA) and the air levels. No detectable P-TDA and E-TDA were found in the two volunteer except for low concentration of 2,4 -TDA in the plasma of one of the volunteers. Among a group of 17 unexposed humans, the U-TDA and P-TDA were below the detection limit.

RESULTS OF THE HYDROLYSIS OF HAEMOGLOBIN

No free 2,4- and 2,6-TDA were seen without hydrolysis. The release of 2,4- and 2,6-TDA increased with increasing hydrolysis time. The specific content of hydrolysable TDI was about 5 -fold greater in albumin compared to haemoglobin.

RESULTS OF THE GEL FILTRATION OF PROTEINS IN ERYTHROCYTES

TDA coeluted with hemoglobin.