4,4'-methylenediphenyl diisocyanate

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 general accepted scientific principles

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2013

Materials and methods

Endpoint addressed:

basic toxicokinetics

Principles of method if other than guideline:

To develop a robust analytical method for the detection of very small amounts of MDI focusing on optimal sensitivity and selectivity

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-isocyanato-4-[(4-isocyanatophenyl)methyl]benzene

Constituent 2

Reference substance name:

benzene, 1,1'- methylenebis[4-isocyanato-]

IUPAC Name:

benzene, 1,1'- methylenebis[4-isocyanato-]

Method

Exposure assessment:

measured

Details on exposure:

To demonstrate the applicability of the method for quantifying values of the specific MDI adduct, two different sample groups were selected. The first group was formed from 25 workers from an MDI plant dealing with MDI during their work shift. The second group was formed from 40 people not knowingly exposed to MDI. Urine and blood samples (EDTA blood collected by venipuncture) were collected during the periodically occurring occupational health examinations at the end of the work shift. The biomonitoring program included the determination of MDA in urine after acid hydrolysis and MDA as a hemoglobine adduct after mild alkaline hydrolysis as well as the detection of the specific hemoglobin aduct ABP-Val-hyd.

Results and discussion

Any other information on results incl. tables

Several haemoglobin samples were analysed to obtain an overview of possible levels of exposure to MDI. In the workers (n = 25) exposed to MDI the specific MDI marker ABP-Val-Hyd was detected in 22 of these samples at 0.15-16.2 pmol/g, whereas MDA derived from hydrolysis was only found in 8 samples in a range between 0.35 and 1.12 pmol/g. In 40 globin samples from people not knowingly exposed to MDI, the amounts of ABP-Val-Hyd were below the LOQ demonstrating the selectivity of the method. It was also demonstrated that the method presented is robust, specific and sensitive for the analytical detection of the specific MDI metabolite ABP-Val-Hyd at a very low level.

Applicant's summary and conclusion

Conclusions:

The results for MDA in urine after acid hydrolysis cover an exposure period of the previous 2 or 3 days. They can only be used as a short-time marker of MDA/MDI exposure after the work shift. As described before, these data do not allow one to distinguish between MDA or MDI exposure. In contrast the ABP-Val-Hyd is a specific and long-time marker for MDI exposure.