HDI Polyisocyanates: Toxicity and Airborne Concentration Guidelines

1
HDI Polyisocyanates Toxicity and Airborne
Concentration Guidelines

• Painting Issues in the Aerospace Industry RT244
• 2000 AIHCE

2
Chemical Structures

• Hexamethylene Diisocyanate(HDI) Monomer
• HDI Biuret (Polyiso)
• Commercial product contains higher mol. wt.
  oligomers and a small percentage of residual HDI
  monomer

3
Chemical Structure

• HDI Isocyanurate Trimer (Polyiso)
• Commercial product contains higher mol. wt.
  oligomers and a small percentage of residual HDI
  monomer

4
Molecular Weight and Vapor Pressure
5
Typical 2-Component PU Paint Formulations
6
Volatility

• HDI polyisocyanate is essentially non-volatile at
  room temperature
• Even at oven temperatures up to 300 F no airborne
  polyisocyanate was found
• Airborne HDI polyisocyanate found only during
  spray application

7
Inhalation Exposure Potential
8
During Paint Application

• Potential for inhalation of HDI monomer is low
  (spray or non-spray)
• Potential for inhalation of HDI polyiso can be
  high during spray application
• Not surprising since there is typically 62-500
  times more polyiso than monomer in the mixed paint

9
Why Study Polyisocyanate Toxicity and Exposure?

• In 2-component (2K) PU paints used as topcoats in
  the aerospace industry, there is isocyanate
  present during application
• Spraying is most common method
• Most of isocyanate groups are on polyiso
• Spray painters most significant isocyanate
  exposure potential is to polyiso aerosol

10
Purpose

• To describe the selection criteria for toxicity
  studies to be used in this evaluation and
• To provide a brief description of the studies and
  the biologic endpoint selected.

11
Selection Criteria for Toxicity Studies

• Test substance is HDI monomer or HDI
  polyisocyanate and not paint formulations
• Common test species across studies
• Route of exposure is inhalation
• Repeated exposure designs preferred to acute
  exposure
• Comparable duration of exposure with analytically
  determined exposure concentrations
• Multiple concentrations (dose response)
• Studies with No-Observed-Adverse-Effect-Level
• Relevance to potential worker exposures

12
Subchronic Toxicity Study Design

• Exposure Regimen
• 6h/day, 5d/wk for 13 wks
• Exposure Atmosphere Characterization
• Air Concentration
• Vapor N-4-nitrobenzyl-N-n-propylamine in midget
  impingers in series HPLC quantification
• Aerosol Filtration nitro-reagent reaction and
  HPLC quantification

13
Subchronic Toxicity Study Design (continued)

• Exposure Atmosphere Characterization
• Particle Size Distribution
• Laser velocimetry
• Cascade impactor
• gravimetric
• chemical analysis

14
Subchronic Toxicity Study Endpoints

• In-life
• Body weights
• Clinical signs
• Urinalysis
• Hematology
• Clinical chemistry
• Post-sacrifice
• Gross pathology
• Organ weights
• Complete histopathology

15
Subchronic Inhalation Toxicity Study with HDI
Monomer

• Test species Fischer 344 rats
• Exposure regimen 0, 0.01, 0.04 0.14 ppm vapor
• Findings Ocular irritation only during
  exposure histopathologic lesions of nasal cavity
• Target organ Respiratory tract
• NOAEL 0.005 ppm or 0.034 mg/m3
  (Estimated from subacute and chronic studies)
• Source Shiotsuka, R.N., 90-day inhalation
  toxicity study with 1,6-hexamethylene
  diisocyanate (HDI) in rats, Bayer Corp., 1988.

16
Subchronic Inhalation Toxicity Study with
Biuret-type HDI Polyisocyanate

• Test species Wistar rats
• Exposure regimen 0, 0.4, 3.5 21 mg/m3
  aerosol
• Particle size distribution 1.4 - 3.3 um MMAD
• Findings increased lung wts proliferative
  lesions in lower lung with septal thickening
• Target organ Respiratory tract
• NOAEL 3.4 mg/m3
• Source Pauluhn, J., Desmodur N 3200,
  Untersuchsungen zur subchronischen
  inhalationstoxizitat an der ratte nach
  OECD-richtline No. 413, Bayer AG, 1988.

17
Subchronic Inhalation Toxicity Study with
Isocyanurate Polyisocyanate

• Test species Wistar rats
• Exposure regimen 0, 0.5, 3.3 26.4mg/m3
  aerosol
• Particle size distribution 1.5 um MMAD
• Findings clinical signs, increased lung wts,
  flow obstruction in pulmonary function tests,
  pulmonary fibrosis
• Target organ Respiratory tract
• NOAEL 3.3 mg/m3
• Source Pauluhn, J., Desmodur N 3300, Study of
  the subchronic inhalation toxicity to rats in
  accordance with OECD Guideline No. 413, Bayer AG,
  1987.

18
Discussion/Summary of Toxicity Studies

• All subchronic studies showed compound-related
  effects due to sequalae of repeated acute
  irritation
• Respiratory tract was the target organ
• Based on mass concentration, the NOAELs for the
  HDI monomer (0.034 mg/m3) was approximately two
  orders of magnitude lower than that for the
  polyisocyanates of HDI (range 3.3 to 3.4 mg/m3)

19
History of Polyiso Tox. And Exp. Studies by
Producers

• Acute inhalation toxicity tests first run in the
  mid 1970s
• 21 day and 90 day inhalation toxicity tests run
  in the mid 1980s
• Workplace air monitoring ongoing since the late
  1970s, both monomer and polyiso

20
UK Isocyanate Control Limits

• 1983, Silk and Hardy paper, Control Limits for
  Isocyanates,Ann. Occup. Hyg. Vol. 27,pp.333-339
• Basic Hypothesis
• Inhalation of aerosols containing polyisocyanates
  is no different from the inhalation of monomer
  vapours as regards their ability to cause adverse
  respiratory effects and sensitization.

21
UK Isocyanate Control Limits

• Control Limits
• 8 hr TWA -- 20ug NCO/m3
• 10 min TWA(STEL) -- 70ug NCO/m3
• We would now refer to this as a TRIG limit as it
  is based on the airborne concentration of Total
  Reactive Isocyanate Groups

22
Total Mass vs. TRIG

• HDI Diisocyanate Monomer
• Total Molecular Mass/Wt. 168
• Mass or wt. Of 2 N, 2 C and 2 O found in the two
  isocyanate functional groups 84
• Therefore, 50 of the mass/wt. is reactive
  isocyanate groups (TRIG)
• Thus a Total Mass Concentration of 0.034 mg/m3
  a TRIG Conc. of 0.017 mg/m3

23
Total Mass vs. TRIG

• HDI Polyisocyanate
• Since the commercial product is a mixture of
  oligomers of varying molecular mass/wt., the
  conversion must be done using a measured NCO
  (TRIG) percentage
• A major HDI polyiso product currently in use has
  an NCO (TRIG) percentage of 21.6
• Therefore, a Total Mass conc. of 0.5 mg/m3 a
  TRIG conc. of 0.11 mg/m3

24
Total Mass vs. TRIG 8 Hour Concentration
Guidelines
Vol/
Vol
T. Mass
TRIG
TRIG
3
3
ppb
mg/m
mg/m
ug/m
3
HDI-
5
0.034
0.017
17
TLV
HDI-UK
5.8
0.04
0.02
20
Oregon
N/A
0.5
0.11
110
PEL
Polyiso
25
Total Mass vs. TRIG STEL/C Conc. Guidelines
Vol/
Vol
T. Mass
TRIG
TRIG
3
ppb
3
mg/m
ug/m
3
mg/m
HDI-UK
20
0.14
0.07
70
MGL
UK-HDI
N/A
0.32
0.07
70
Polyiso
Oregon
N/A
1.0
0.22
220
PEL
Polyiso
26
Why Not Accept Silk Hardy Hypothesis?

• At the time (1983) only acute LC50 data was
  available and monomer and polyiso results were
  quite similar
• BUT, workers are not exposed to hundreds of
  mg/m3(LC50 range)
• Janko (AIHAJ 1992) and Myer (AIHAJ 1993) reported
  workplace ranges of lt1 to 30mg/m3 (or lt1 to 6.5
  mgTRIG/m3) of airborne HDI polyisocyanate.

27
Why Not Accept Silk Hardy Hypothesis

• Subchronic inhalation toxicity tests were run on
  HDI monomer, HDI biuret and HDI trimer in the mid
  80s.
• These studies exposed the animals to
  polyisocyanate concentrations in the same range
  as was found in field survey studies (Janko and
  Myer)

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Monomer vs. Polyiso Toxicity Comparison
29
No Difference Hypothesis Wrong

• At concentrations and exposure patterns like
  those found in the workplace, the rat studies
  showed that NCO groups found on HDI
  polyisocyanate molecules were clearly much less
  toxic than an equal number of diisocyanate
  monomer NCO groups.
• In other words, in this case, the Silk and Hardy
  no difference hypothesis is clearly wrong.

30
Conclusion

• Measuring airborne TRIG concentrations
  non-specifically in an HDI polyisocyanate spray
  painting operation and comparing the results to
  the UK-HSE control limits would greatly
  overestimate the risk (42 fold).
• On the other hand, a good TRIG method may be
  useful for thermal decomposition situations.