4,4'-methylenediphenyldiisocyanate and 2,4'-diisocyanatodiphenylmethane and their oligomerisation reaction products with 2,2'-oxydiethanol, propane-1,2-diol and butane-1,3-diol

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

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:

Determination of a new biomarker in subjects exposed to 4,4'-methylenediphenyl diisocyanate.

Author:

Sabbioni G, Dongari N and Kumar A;

Bibliographic source:

Biomarkers, 15(6): 508-515

Materials and methods

Endpoint addressed:

basic toxicokinetics

Principles of method if other than guideline:

Development of a liquid chromatography (LC) mass spectrometry (MS/MS) procedure for determination of isocyanate-specific albumin adducts in humans.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-methylenediphenyl diisocyanate

EC Number:

202-966-0

EC Name:

4,4'-methylenediphenyl diisocyanate

Cas Number:

101-68-8

Molecular formula:

C15H10N2O2

IUPAC Name:

1,1'-methylenebis(4-isocyanatobenzene)

Constituent 2

Reference substance name:

Reference substance 001

Method

Exposure assessment:

measured

Details on exposure:

Blood and urine were collected from two worker groups. Workers were recruited from a chemical factory (= MDI workers, Schutze et al. 1995) and from construction sites (Sabbioni et al, 2007). The MDI workers (27 men) were exposed to MDI, age median 32 (range 20-57). The construction site workers (62 men and 3 women) were exposed to MDI and prepolymer products. The median age (range) of the workers was 32.9 (20.1-59.6) years. At the beginning of the study, 40 workers (controls) had not been exposed to isocyanate products in the last 4 months and 25 workers has been exposed. Biological samples wiere collected from 65 workers (40 controls, 25 exposed) at the beginning of the study. After 4-7 months of exposure to isocyanate, blood samples from 19 former controls were obtained.

Results and discussion

Results:

The isocyanate-specific adduct with albumin, MDI-Lys, could be found in 62.5 %, 63.6% and 15% of the MDI workers, exposed construction workers and control construction workers, respectively. The acetylated metabolite AcMDI-Lys was found in 4.2 %, 29.5 % and 0 % of the MDI workers, exposed construction workers and control construction workers, respectively. Differences between the MDI workers and the exposed construction workers compared with the control workers were significantly (p <0.01) higher. No significant differences (p< 0.01) were observed between both exposed worker groups. The MDI-Lys levels, 25th, 50th, 75th, 90thpercentile, in the exposed construction and MDI workers were 0, 65.2, 134, 244 fmol/mg and 0, 30.5, 57.4, 95.8 fmol/mg, respectively. Correlation analysis between different biomarkers revealed a good correlation for the construction workers between the urinary metabolites and MDI-Lys. The correlation with the haemoglobin adduct is much smaller.