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

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Expert review: does not include experimental toxicological data

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2007

Materials and methods

Study type:

other: Review paper

Test material

Test material information

Constituent 1

Reference substance name:

9016-87-9

Cas Number:

9016-87-9

IUPAC Name:

9016-87-9

Constituent 2

Reference substance name:

Isocyanic acid, polymethylenepolyphenylene ester

IUPAC Name:

Isocyanic acid, polymethylenepolyphenylene ester

Details on test material:

Commercial Diisocyanates

Method

Type of population:

other: not applicable

Subjects:

not applicable

Clinical history:

not applicable

Controls:

not applicable

Route of administration:

other: not applicable

Details on study design:

The objectives of this review are to describe and critique the various methodologies employed in diisocyanate antibody testing, to examine the utility of such testing as a diagnostic tool or marker of exposure, and to offer suggestions for improving test performance and interpretability. The focus on three diisocyanates, toluene diisocyanate (TDI), 4,4'-diphenylmethane diisocyanate (MDI), and hexamethylene diisocyanate (HDI), reflects the widespread usage of these monomers and the extent of publications pertaining to their immunogenicity.

Results and discussion

Results of examinations:

This paper reviews the available literature on immunoassay detection of IgE and IgG binding to diisocyanate-protein conjugates and examine the utility of such testing as a diagnostic tool for OA and exposure indicator to diisocyanates.
Data from 29 studies of occupational exposure to diisocyanate revealed considerable variability in test methodology and heterogeneity in the reported prevalence of positive test responses across studies. Positive IgE responses identified cases with low sensitivity (18-27%) and high specificity (96-98%). IgG binding to diisocyanates is an indirect , qualitative indicator of disease status and past exposure. However, the utility of these assays is limited due to lack of (1) method standardization, (2) population norms to guide interpretation of result , and (3) demonstrations that the assays improve either on disease prediction or on exposure confirmation beyond other indicators.

Any other information on results incl. tables

Table 6
Prevalence of specific IgE and IgG antibodies by conjugate and symptom status
Occupational exposure to any diisocyanate excluding subjects with an OA diagnosis (a)
.	Exposed no symptoms		Exposed		Exposed with symptoms
Antibody class & conjugate	Positive/tested	No.of Studies	Positive/tested	No. of Studies	Positive/tested	No. of Studies
IgE	.	.	.	.	.	.
HDI	0/163 = 0%	3	56/1,356 = 4%	9	8/241 = 3%	3
MDI	0/189 = 0%	4	35/1,330 = 3%	7	11/268 = 4%	5
TDI	8/393 = 2%	7	36/824 = 4%	4	12/303 = 4%	7
IgG	.	.	.	.	.	.
HDI	-	-	68/438 = 16%	6	7/24 = 29%	1
MDI	4/48 = 8%	2	45/589 = 8%	4	4/51 = 8%	3
TDI	18/173 = 10%	2	8/109 = 7%	2	5/50 = 10%	4

(a) Insufficient data to perform stratified analysis of exposure subgroups controlling for laboratory.

Applicant's summary and conclusion

Conclusions:

Antibody testing is appealing due to its accessibility and relatively low cost, as well as the absence of potential side effects for the patient, but unlike high molecular weight (HMW) agents, these serologic markers are insensitive and non-specific for disease detection.