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Sensitisation data (human)

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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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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.