Table 1.

Adaptation of LaKind scoring criteria for isocyanates mini-review. Each paper was scored from 1 (Tier 1) to 3 (Tier 3) for each of the eight components, giving total possible scores from 8 (highest quality) to 24 (lowest quality).

Assessment component	Tier 1	Tier 2	Tier 3
Study participants	>20 occupationally exposed individuals	5–20 occupationally exposed individuals	Any other study (<5 occupationally exposed individuals, volunteers, general population)
Chemicals under investigation	HDI, TDI, and/or MDI	IPDI and NDI	Any other isocyanates
Exposure biomarker and matrix	Biomarker in a specified matrix has accurate and precise quantitative relationship with external exposure, internal dose, or target dose e.g. diamines and Hb adducts.	Evidence exists for a relationship between biomarker in a specified matrix and external exposure, internal dose, or target dose but limited application e.g. other protein adducts or conjugates.	Biomarker in a specified matrix is a poor surrogate (low accuracy and precision) for exposure/dose e.g. experimental biomarkers, non-specific markers such as general effect markers.
Biomarker specificity	Biomarker is derived from exposure to one parent chemical.	Biomarker is derived from a limited number of parent chemicals, such as diamines.	Biomarker is derived from multiple parent chemicals with varying types of adverse endpoints.
Technique	Instrumentation that provides unambiguous identification and quantitation of the biomarker at the required sensitivity [e.g. gas chromatography–mass spectrometry [GC–MS), GC–MS/MS, and liquid chromatography (LC)–MS/MS].	Instrumentation that allows for identification of the biomarker with a high degree of confidence and the required sensitivity [e.g. GC–MS and GC–electron capture detector (GC–ECD)].	Instrumentation that only allows for possible quantification of the biomarker but the method has known interferants (e.g. GC–FID, spectroscopy).
Method characteristics—Any specific weaknesses in study design leading to a Tier 3 score to be noted	Acceptable level of detection (LoD)		LoD above current state-of-the-art.
	Samples with a known history and documented stability data or those using real-time measurements.	Stability not specifically assessed, but samples were stored appropriately and analysed promptly.	Specific reason to query stability. E.g. samples with unknown history or known issues.
	Samples are contamination-free from time of collection to time of measurement (e.g. by use of certified analyte-free collection supplies and reference materials, and appropriate use of blanks both in the field and lab). Research includes documentation of the steps taken to provide the necessary assurance that the study data are reliable.	Study not using/documenting these procedures.	There are known contamination issues and no documentation that the issues were addressed.
Quality assurance	Study has used external QA where appropriate	Some QA used (note details)	No QA
Matrix adjustment	Study includes results for adjusted and non-adjusted concentrations if adjustment is needed. 24 h total urine collection is considered Tier 1.	Study only provides results using one method (matrix-adjusted or not).	No established method for adjustment (e.g. adjustment for hair, saliva).