Hazardous Chemical Information System (HCIS)

Isocyanates

E/S first adopted in 1990

Sensitiser notice: Some substances can cause a specific immune response in some people . Such substances are called sensitisers and the development of a specific immune response is termed `sensitisation' . Exposure to a sensitiser, once sensitisation has occurred, may manifest itself as a skin rash or inflammation or as an asthmatic condition, and in some individuals this reaction can be extremely severe . See Chapter 12: Guidance Note on the Interpretation of Exposure Standards for Atmospheric Contaminants in the Occupational Environment, published by Worksafe Australia .

Documentation notice: National Occupational Health and Safety Commission documentation available for these values.

No standard should be applied without reference to Guidance on the interpretation of Workplace exposure standards for airborne contaminants.

Notes:

1) Isocyanates are not normally detected by odour until the concentration reaches 10 to 20 times the exposure standard . To determine the airborne concentrations of isocyanates , HSE ⁽¹⁾ and NIOSH⁽²⁾ methods are available.

2) Several comprehensive reviews have been made on the health effects of individual isocyanates . It is, therefore, not the intention of this documentation to exhaustively review all scientific literature related to specific isocyanates , but to summarise the available quantitative dose-response information, especially on isocyanate prepolymers , and to substantiate the Exposure Standards Working Group's approach of adopting a generic exposure standard for this class of compounds . Interested readers should refer to the References and Further Reading for detailed information on the health effects of individual isocyanates and the relationship between this generic exposure standard and the corresponding overseas limits.

1.       IDENTITY

An isocyanate is a compound which contains the -NCO group . It may be represented by the general formula R-N=C=O . An isocyanate reacts with the hydroxyl group of an alcohol to form a urethane:

R-NCO + R'OH ---------> R- NHCOOR '

The more common isocyanate compounds used in industry are:

1.1       Toluene di-isocyanate ( TDI )

1.2       Methylene bisphenyl isocyanate (MDI)

1.3       Hexamethylene di-isocyanate ( HDI )

1.4       Polymethylene polyphenyl isocyanate ( PAPI )

1.5       Isophorone di-isocyanate ( IPDI )

1.6       1 ,5 -Naphthalene di-isocyanate ( NDI )

1.7       Methylene bis -(4-cyclohexylisocyanate)

1.8       Polyisocyanates ( Isocyanate prepolymers )

2.       CHEMICAL AND PHYSICAL PROPERTIES

In the production of a polyurethane resin, the reaction is generally between a di-isocyanate and a polymeric hydroxyl compound such as a polyether or polyester resin:

OCN -R-NCO + 2HOR'OH --------- > R'COONH-R-NCHCOOR '

The reaction is exothermic . Catalysts, such as tertiary amines and organotin derivatives are normally added to initiate the reaction.

The chemical and physical properties of the more common isocyanate compounds used in industry are described briefly below:

2.1       Toluene di-isocyanate ( TDI )

TDI is generally a colourless to pale yellow liquid with a sharp pungent smell . The liquid consists of a mixture of 2,4 and 2,6 isomers in the proportion of 65:35 or 80:20 . Its chemical and physical properties include:

2.2       Methylene bisphenyl isocyanate (MDI)

Commercial grades of MDI are usually dark brown, viscous liquid, but MDI may also be found in pure form as white to light yellow, odourless flakes . Its chemical and physical properties include:

2.3       Hexamethylene diisocyanate ( HDI )

HDI is a liquid at room temperature . Its chemical and physical properties include:

2.4       Polymethylene polyphenyl isocyanate ( PAPI )

PAPI is a dark amber, viscous liquid with very low volatility and a slower reactivity rate than many common aromatic diisocyanates . Its chemical and physical properties include ⁽³⁾ :

2.5       Isophorone diisocyanate ( IPDI )

IPDI is a colourless to slightly yellow liquid with a low vapour pressure . Its chemical and physical properties include:

2.6       1 ,5 -Naphthalene di-isocyanate ( NDI )

NDI is a white to light yellow powder . Its chemical and physical properties include:

2.7       Methylene bis -(4-cyclohexylisocyanate)

Its chemical and physical properties include:

2.8       Polyisocyanates ( Isocyanate prepolymers )

Diisocyanates , such as HDI , TDI , or IPDI , can be reacted with related polyfunctional monomers to yield high molecular-weight isocyanate prepolymers . These prepolymers have lower vapour pressures, react more slowly than the parent monomers; the rate of cure can be varied by means of temperature and catalysis . From aliphatic prepolymers (for example, HDI -derived prepolymers ), polyurethanes with non-yellowing properties, that is, stability to sunlight and ultraviolet light, can be produced.

Isocyanate pre-polymers are usually supplied commercially as solutions in non-reactive solvents such as ethyl acetate, cellosolve acetate, xylene etc . Residual monomer in the prepolymer is usually less than 0.7% w/w ⁽⁴⁾ .

3.       MAJOR INDUSTRIAL USES

3.1       Diisocyanate monomers

The aromatic diisocyanates TDI and MDI are the essential building blocks of flexible and rigid polyurethane foams respectively . Diisocyanates are also used in industry for the production of synthetic rubbers and elastomers, foundry core binders (in a cold cure process), and special purpose adhesives and printing inks, and in the preparation of 'polyurethane oils', the product of vegetable oil, polyol and TDI .

3.2       Isocyanate prepolymers

The isocyanate prepolymers are usually used in 'two-pack', polyurethane paints in the building and the automobile re-finishing industries . This two-pack system consists of a isocyanate prepolymer (frequently derived from an aliphatic isocyanate monomer, for example, HDI or IPDI ) and a polymer with available hydroxyl groups, as two separate components . When the two parts are mixed, the polymerisation process is relatively slow and may take hours or days depending on the temperature and humidity.

Note: The amount of unreacted isocyanate monomer present in the polyisocyanate component is usually of the order of 0.5% and does not itself give rise to a hazardous vapour when applied by brush or roller at room temperature . However, when such paints are applied by spray (as in car refinishing), the aerosol mist droplets produced are mainly in the respirable range and these aerosols contain all the functional isocyanates present in the formulation . Control measures are necessary to avoid an inhalation hazard.

4.       DI- ISOCYANATE MONOMERS

4.1       Health Effects

Isocyanate splashes in the eyes can cause severe chemical conjunctivities . Isocyanates are also mild skin irritants and can cause dermatitis . Sensitisation of the skin may occur, but this is not common . ⁽⁴⁾

In sufficiently high concentrations in the air, isocyanates have a primary irritant effect on the respiratory tract . Asthmatic attacks may occur either immediately on exposure or some hours later . Some workers may become sensitised and exhibit asthmatic symptoms when subsequently exposed to atmospheric concentrations well below the exposure standard . There is evidence ⁽⁵⁾ that for susceptible workers, recurrent exposures may result in impairment of ventilatory function.

The American Conference of Governmental Industrial Hygienists ( ACGIH ) has produced documentation ⁽⁵⁾ for TDI , MDI, HDI , IPDI and methylene bis -(4-cyclohexylisocyanate) . The Exposure Standards Working Group has reviewed these documentations and agreed to adopt these reviews as the basis for setting exposure standards for isocyanates . Interested readers are encouraged to refer to these documentations for detailed dose-response information.

4.2       Overseas Exposure Standards

The UK Health & Safety Executive ( HSE ) has adopted a two-part maximum exposure limit for organic isocyanates : 8-hour TWA of 0.02mgNCO/m³ and 10-min STEL of 0.07mgNCO/m^{3 (6,7)} . These exposure standards for isocyanates are defined in terms of the functional -NCO group, so that for the first time all isocyanate compounds are brought within the scope of a common unifying standard.

The ACGIH TLVs ⁽⁵⁾ for diisocyanates , and their corresponding values in terms of functional -NCO group, are given in the following table . It is evident that there is practically little difference between the ACGIH and HSE standards.

ACGIH TLVs for Diisocyanates (89-90)

5.       HEALTH EFFECTS OF ISOCYANATE PREPOLYMERS

The UK Employment Medical Advisory Service believes that isocyanate prepolymer aerosols have the same ability as the monomer vapours to cause adverse respiratory effects and sensitisations . ⁽⁷⁾ Reports ^{(8 ,9 )} have shown that inhalation of relatively non-volatile isocyanates in the form of dusts and spray-mists could cause adverse respiratory effects.

In UK , many cases of respiratory impairment and sensitisation have been reported ⁽¹⁰⁾ in workers who were exposed to aliphatic isocyanate prepolymers when using two-pack polyurethane paint for the spray painting of cars . In Japan , a case of sensitisation caused by spray-application of aromatic isocyanate prepolymer -based paint has been reported ⁽¹¹⁾ .

A theoretical argument has been proposed ⁽¹²⁾ that prepolymers are bulkier and should react at a slower rate with human tissues than monomer molecules and therefore may have reduced potential to cause irritation and sensitisation . However, this argument is not supported by any quantitative dose-response data.

6.       CONCLUSION

Isocyanates are respiratory irritants . Acute exposures can cause asthmatic attacks . Some workers may become sensitised and exhibit asthmatic symptoms when subsequently exposed to very low atmospheric concentrations.

The Exposure Standards Working Group agrees to adopt the recommendations made in the ACGIH Documentation ⁽⁵⁾ for diisocyanates : TDI , MDI, HDI , IPDI and methylene bis -(4-cyclohexylisocyanate) . These ACGIH TLVs for diisocyanates are in remarkably good agreement with the HSE's generic maximum exposure limit for all isocyanates : 8-hour TWA of 0.02mgNCO/m³ and 10-min STEL of 0.07mgNCO/m³ . A generic exposure standard has the advantage of broader coverage, especially useful for application for mixtures of isocyanates which apparently share the same toxicological properties.

There is also evidence to indicate that isocyanate prepolymer aerosols can be as hazardous as the diisocyanate monomers in causing adverse respiratory effects and sensitisation.

7.       RECOMMENDATION FOR EXPOSURE STANDARD

After reviewing all the relevant information, the Exposure Standards Working Group recommends a generic exposure standard for all isocyanates : a TWA of 0.02mgNCO/m³ and STEL of 0.07mgNCO/m³ . These levels should be low enough to prevent sensitisation to most workers, but are not low enough to prevent attacks after sensitisation has occurred . This exposure standard covers isocyanate prepolymers and all functional isocyanate -group containing compounds . The reader is encouraged to review the section on Sensitisers in the Guidance Note on the Interpretation of Exposure Standards for Atmospheric Contaminants in the Occupational Environment for a more detailed discussion of sensitisation.

REFERENCES

1. Health and Safety Executive (UK), Organic isocyanates in air - Laboratory method using 1-(2-methoxyphenyl) piperazine solution and high performance liquid chromatography, Methods for the Determination of Hazardous Substances, MDHS 25, HSE , London , March 1987

2. National Institute for Occupational Safety and Health (NIOSH), NIOSH Manual of Analytical Methods, 3rd edition, edited by Eller PM, Volume 1, DHHS (NIOSH) Publication No.84-100, Method 5505 (5/15/85), Ohio, 1984

3. Woolrich PF, "Toxicology, industrial hygiene and medical control of TDI , MDI and PMPPI ", Am Ind Hyg Ass J, 43, 89-97, 1982

4. Health and Safety Executive (UK), Isocyanates : toxic hazards and precautions, Guidance Note EH/16, HMSO, London , 1979

5. American Conference of Governmental Industrial Hygienists ( ACGIH ), Documentation of the threshold limit values and biological exposure indices, 5th edition, Cincinnati , 1986

6. Health and Safety Executive (UK), Occupational exposure limits 1989, Guidance Note EH40/89, HMSO, London , 1989

7. Silk SJ & Hardy HL, "Control limits for isocyanates ", Ann Occup Hyg , 27, 333-339, 1983

8. Kozen RB et al, "Human response to low concentrations of p ,p' -diphenylmethane di-isocyanate (MDI)", Am Ind Hyg Assoc J, 27, 121-127, 1966

9. Peterson JE et al, "Health hazards of spraying polyurethane foam out-of-doors", Am Ind Hyg Assoc J, 23, 345-352, 1962

10. Tyrer FH, "Hazards of spraying with two-pack paints containing isocyanates ", J Soc Occup Med 29, p.22-24, 1979

11. Hayakawa M et al, "A case of occupational asthma due to polyurethane", Nippon Kyoshitsu Kai Shi, 17, 421-425, 1979 (in Japanese, HSE translation No. 9605)

12. Pisaniello D, "Hazards Associated with the use of two-pack polyurethane spray paints in auto refinishing", Australian Institute of Occupational Hygienists Newsletter, Victoria, June 1989

FURTHER READING

1. Alexandersson R et al, "Exposure, lung function and symptoms in car painters exposed to hexamethylene-diisocyanate and biuret modified hexamethylene-diisocyanate ", Arch Env Health, 42, 367-373, 1987

2. Charles J et al, "Hypersensitivity pneumonitis after exposure to isocyanates ", Thorax, 31,127-136, 1976

3. Clarke CW & Aldons PM, " Isophorone diisocyanate induced respiratory disease", Aust N Z Med, 11, 290-292, 1981

4. Hardy HL & Devine JM , "Use of organic isocyanates in industry - some industrial hygiene aspects", Ann Occup Hyg 22, 421-427, 1979

5. Lozewicz S et al, "Outcome of asthma induced by isocyanates ", Br J Dis Chest, 81, 14-22, 1987

6. Musk A et al , " Isocyanates and respiratory disease: current status", Am J Ind Med 13, 331-349, 1988

7. National Institute for Occupational Safety and Health (NIOSH), Criteria for a recommended standard - occupational exposure to diisocyanates , DHEW Pub No.(NIOSH) 78-215, 1978

Footnotes:

Documentation notice:

Entries carrying a notice for National Occupational Health and Safety Commission documentation indicate that these substances have been reviewed in detail by the Exposure Standards Expert Working Group and that documentation supporting the adopted national values is available in the National Commission's Documentation of the Exposure Standards [NOHSC:10003(1997)].