Overview of NIOSH Method 5525 

and DAN Method for Total 

Isocyanate Determination

Robert P. Streicher

NIOSH
Disclaimer

Mention of company names and/or products 

does not constitute endorsement by the 

Centers for Disease Control and Prevention. 

The findings and conclusions in this 

presentation are those of the authors and do 

not necessarily represent the views of the 

National Institute for Occupational Safety 

and Health.
Common Diisocyanate Monomers

H2

O C N C N C O

CH3 O

CH3

N

C

O

N

C

O

O

MDI

2,6-TDI

CH3

N

N

C

O

C

O

N

N

C

O

C

O

N CH3 CH3

C

H2

N C O

O C

H3C

C

H2

O C N N C O

HDI

IPDI

HMDI

2,4-TDI
Total Isocyanate

• All species with free (unreacted) isocyanate 

groups

• Monomer (MDI)

• Polymeric MDI (pMDI) – crude mixture of MDI 

monomer and higher oligomers

• MDI prepolymer – product of polyol + excess of 

MDI or pMDI

• Partial reaction products during polyurethane 

production 
Importance of Measurement of Total 

Isocyanate versus Monomer only

• Recognition that not only monomeric 

isocyanates present exposure hazards

• Measurement Measurement of monomeric monomeric isocyanate isocyanate may 

not be a good surrogate for total isocyanate 

exposure

• Monomer may represent small percentage 

of isocyanate product (e.g. prepolymers) 
Air Sampling Recommendations

for MDI/pMDI

• Impingers

– Used for fast-cure particles > 2 μm

- Typical for spray of MDI/pMDI

- Acceptable for vapor collection

• Reagent-coated Filters

– Preferred for vapor collection

– Used for:

- All particles < 2 μm

- Slow-cure particles > 2 μm

– Extract filters in the field

– High-boiling solvent on filters (?)
NIOSH Method 5525 –

MAP Derivatizing Reagent

N

H

N

CH2

N

1-(9-Anthracenylmethyl)piperazine (MAP)
Advantages of MAP

• Derivatization - reacts rapidly with 

isocyanates

• Chromatography - pH gradient

• Indentification - sensitive and selective 

by UV/FL

• Quantification - universal UV response 

factor
Polymeric MDI Bulk
How the DAN Method Works

NH2

NH2

N

NH2

H

+

DAN acetic

R

N

C

O

C

O

N

H

R

N

H

H

N

R NH2 +

acetic

acid

DAN

1H-Perimidin-2(3H)-one

C O
Evaluation of DAN Chemistry

• Works well for aromatic isocyanate systems 

(MDI and TDI)

• Problems with quantitative reaction in 

aliphatic systems (HDI)
Goals of Analytical Method 

Development for Perimidone

• High accuracy

• Covers a broad concentration range

• Covers a broad range of isocyanate species

• Simple and inexpensive: interpretation-free
Mass Spectrum of Perimidone

184

Abundance 166

10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200

166

139 155 83 92

101 128 51 63 75 113

m/z

Abundance
Perimidone and

Deuterated Perimidone

NH

C

HN

O

NH

C

HN

O

HN NH

H

H

H H

H

H

D

D

D D

D

D

MW = 184 MW = 190
Total Ion Current Chromatogram of 

2.5 ug/mL Perimidone + 30 ug/mL 

Deuterated Perimidone

Time → 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00

Abundance
Mass Spectrum of Sample 

Containing Perimidone and 

Deuterated Perimidone

190

155 160 165 170 175 180 185 190 195 200

Abundance 184

172

166

161

m/z

187
Acknowledgments

Kathy Ernst, Fariba Nourian (NIOSH)

Dr. Dhimiter Bello (U. of Mass. Lowell)
Uncertainties in Exposure 

Assessment and Research Gaps 

Related to use of MDI Foam 

Insulation
How Important is Dermal Exposure in 

Respiratory Sensitization?

• Animal studies are definitive

• Observed respiratory sensitization in environments 

with little or no inhalation exposure

• Bello et al., Skin Exposure to Isocyanates: 

Reasons for Concern, Environ. Health 

Perspectives 115: 328-335 (2007).
Research Questions in Application 

of MDI-based Foam Insulation

• What is the lifetime of isocyanates on the surface 

of foam?

• What is the exposure hazard (inhalation and/or 

dermal) from cutting newly hardened foam 

insulation?

• How important are isocyanate groups chemically 

bound (as opposed to adsorbed) to foam surfaces 

of dust?

• How can chemically-bound isocyanate groups be 

measured?
Thermal Breakdown of 

Polyurethane Foam can present an 

Exposure Hazard

• Thermal breakdown of polyurethane 

produces various isocyanate species 

including monomer, aminoisocyanates, low 

molecular weight isocyanates.

• May occur when manipulating cured foam 

or working on adjacent fixtures.

• Isocyanate exposure hazard is not 

recognized by worker or homeowner