Skip directly to site content Skip directly to search


Español  Other Languages


An official website of the United States government Here's how you know
 Official icon**Official websites use .gov**
				A .gov website belongs to an official government organization in the United States. Lock icon**Secure .gov websites use HTTPS**
				A lock (  ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People
	CDC LogoCDC Logo
 Search

		×
			NIOSH
			NIOSH

				All CDC
				Submit


The National Institute for Occupational Safety and Health (NIOSH)





Current Intelligence Bulletin 8: 4,4 – Diaminodiphenyl -methane (DDM)						Print
																Related Pages
										January 30, 1976
DHHS (NIOSH) Publication Number 78-127
Department of Health, Education, and Welfare
Public Health Service
Center for Disease Control
National Institute for Occupational Safety and Health
5600 Fishers Lane
Rockville, Maryland 20852
The enclosed background material on 4,4′-diaminodiphenylmethane (DDM) has been prepared by the Office of Extramural Coordination and Special Projects, National Institute for Occupational Safety and Health to alert members of the occupational health community to new information on a potential occupational hazard.
Your comments and suggestions for changes to future reports are solicited.
Sincerely yours,*[signature]*
John F. Finklea, M.D., Director
National Institute for Occupational Safety and Health
Summary
This office has prepared the following summary of information on the production, uses, exposure and health effects of 4,4′-diaminodiphenylmethane (DDM).
DDM, 4,4′-diaminodiphenylmethane, also known as p,p’-methylenedianiline (MDA), is an important chemical intermediate. Over 200,000,000 pounds per year of DDM are manufactured in the United States. A list of the manufacturers and producers of DDM is attached. DDM is produced by the condensation of aniline with formaldehyde in the presence of an acid catalyst.
Approximately ninety-nine percent of the DDM produced is consumed in its crude form (occasionally containing not more than 50% DDM and polyDDM) at its production site by reaction with phosgene in the preparation of isocyanates and polyisocyanates. These isocyanates and polyisocyanates are employed in the manufacture of rigid polyurethane foams which find application as thermal insulation. Polyisocyanates are also used in the preparation of the semiflexible polyurethane foams used for automotive safety cushioning.
DDM is also used as:
an epoxy hardening agent
a raw material in the production of polyurethane elastomers
in the rubber industry
a curative for neoprene1
an anti-frosting agent (anti-oxidant) in footwear
a raw material in the production of Qiana Nylon
a raw material in the preparation of poly(amide-imide) resins (used in magnet wire enamels)It is estimated that 2,500 workers are exposed to DDM. Many of these exposures to DDM are in the preparation of isocyanates and polyisocyanates and, on construction sites, in the application of epoxy coatings.
In 1965, the hepatotoxic effects of DDM in humans were first seen in the so-called “Epping Jaundice” outbreak in Great Britain. In this incident 84 people who had eaten DDM contaminated bread, experienced hepatocellular damage evidenced by elevated SGOT and SGPT levels.2,3 has also been shown to produce liver lesions in a group of intragastrically fed rats4 and has caused liver degeneration and spleen lesions in another group of DDM fed rats.5
DDM in the occupational environment has been implicated in a number of cases of toxic hepatitis. During an 18 month period beginning April 1972, six cases of hepatitis developed among about 300 men who used epoxy resins in the construction of a nuclear power plant in Alabama. Two chemicals, DDM and 2-nitropropane, were held suspect in this study.6,7 another study, 13 cases of hepatitis developed between 1966 and 1972 among workers who added DDM to a mixture to produce a hard plastic insulating material. All of these men became ill within a few days of working intensively with DDM.8 One other case of hepatitis, possibly associated with DDM, was reported by a person who wrote to the Environmental Protection Agency describing an episode of acute hepatitis as well as CNS and pulmonary symptoms he experienced following exposure to a surfacing agent containing DDM.
The carcinogenic effects of DDM have also been studied. In one study, 16 rats were given 4 or 5-20 mg DDM doses by stomach tube over 8 months. A hepatoma and a haemangioma like tumor of the kidney were found in one rat after 18 months and an adenocarcinoma of the uterus was found in another after 24 months.9 another report, of 48 rats given DDM intragastrically 5 times weekly, all developed liver cirrhosis, four developed hepatomas (2 benign) and others, miscellaneous tumors.10 a third report, 50% of 50 DDM injected rats developed tumors (4 hepatomas) compared with 26% of a control group.11 have been no reported human cancers associated with DDM.
If, as hypothesized in the Center for Disease Control study of nuclear power plant construction workers, not all workers are susceptible to liver injury after exposure to DDM, and if the 1-2% incidence of liver disease seen in this study were applied to all workers with possible exposure to DDM, we would expect to see 25 to 50 cases of DDM associated toxic hepatitis a year.

Listed Manufacturers and Producers of 4,4′-Diaminodiphenymethane
Listed Manufacturers and Producers of 4,4′-Diaminodiphenymethane
Company
Plant LocationAllied Chemical Corporation
Specialty Chemicals Division
Moundsville, West VirginiaDow Chemical, U.S.A.
Midland, MichiganJefferson Chemical Company, Inc.
Port Neches, TexasMobay Chemical Corporation
New Martinsville, West Virginia
Cedar Bayou, TexasRubicon Chemicals, Inc.
Geismar, LouisianaUniroyal, Inc.
Uniroyal Chemical Division
Naugatuck, ConnecticutThe Upjohn Company
Polymer Chemicals Division
La Porte, Texas*Adapted from the following sources:*
1975 Directory of Chemical Producers, Stanford Research Institute, Menlo Park, California, page 818, 1975. Synthetic Organic Chemicals, U.S. Production and Sales, 1973, U.S. International Trade Commission, ITC Publication 728, U.S. Government Printing Office, Washington, D.C., pages 23, 41, and 139, 1975.
References
Lloyd, J. William, DeCoufle, Pierre, and Moore, Roscoe M., Jr. Current Intelligence — Background Information on Chloroprene. Journal of Occupational Medicine, 17:263-265, 1975.
Kopelman, H., Robertson, M. H., Sanders, P. G., and Ash, I. The Epping Jaundice. Brit, Med. J., 1:5149 1966.
Kopelman, H., Scheuer, P. J., and Williams, R. The liver lesion of the Epping Jaundice. Quart. J. Med., 35:553, 1966.
Gohlke, R. and Schmidt, P. 4-4′-Diaminodiphenyl methane: , enzyme histochemical and autoradiographic investigations in acute and subacute experiments in rats with and without the additional stress of heat. Int. Arch. Arbeitsmed, 32(3):217-31, 1974.
Pludro, G., Karlowski, K., Mankowska, M., Woggon, H., and Udhe, W. J. Toxicological and Chemical Studies of Some Epoxy Resins and Hardeners I. Determination of acute and subacute toxicity of phtalic acid anhydride, 4-4′-diaminodiphenylmethane and of the epoxy resin: EG-34. Acta Poloniae Pharmaceutica, 26(4):352-57, 1969.
Unpublished data, Center for Disease Control, 1974.
Williams, Sankey V., Bryan, John A., and Wolf, Frederick S. Toxic Hepatitis and Methylenedianiline. New Eng. J. of Med., Vol. 291:1256, 1974.
McGill, D. B. and Motto, J. D. An industrial outbreak of toxic hepatitis due to Methylenedianiline. New Eng. J. of Medicine, 291(6):278-82, 1974.
Schoental, R. Carcinogenic and Chronic Effects of 4-4′-diaminodiphenylmethane, an epoxy resin hardener. Nature, 219:1162-63, 1968.
Munn, A. Occupational Bladder Tumors and Carcinogens: Developments in Britain, In: , W. and Lampe, K. F., eds., *Bladder Cancer. A Symposium,* Birmingham, Alabama, Aesculapius, p. 187.
Steinhoff, D. and Grundmann, E. Zur Cancerogenen Wirkung von 4-4′-diaminodiphenylmethan und 2,4′-diaminodiphenylmethan. Naturwissenschaften, 57:247-48, 1970.
							
					
							Last Reviewed:  June 6, 2014						Source: 	National Institute for Occupational Safety and Health
					Facebook
        Twitter
        LinkedIn
        Syndicate homeNIOSH Publications & Products
NIOSH-Issued Publications
Search NIOSHTIC-2 Research Database
Docket
Documents for Public Review
Peer Review Agenda
Databases
eNews
Federal Register Noticesplus icon
FRN Archive 2007-2010
FRN Archive 2005-2006
FRN Archive 2001-2004
FRN Archive 1996-2000
Press Releases and Updatesplus icon
Press Release Archives 2010-2013
Press Release Archives 2006-2009
Press Release Archives 2001-2005
Press Release Archives 1998-2000
Press Release Archives 1992-1997
Regulations
Regulatory Agenda
Science Blog
Software
Video Error processing SSI file  Follow NIOSH Facebook
Pinterest
Twitter
YouTube
 NIOSH Homepage NIOSH A-Z
Workplace Safety & Health Topics
Publications and Products
Programs
Contact NIOSH


About CDC
					Contact Us
					800-232-4636
 Facebook Twitter Instagram LinkedIn Youtube Pinterest Snapchat
 CONTACT CDC
				Contact Us
							Call 800-232-4636
							Email Us
			ABOUT CDC
				About CDC
							Jobs
							Funding
			POLICIES
				Accessibility
							External Links
							Privacy
							Policies
							No Fear Act
							FOIA
							OIG
							Nondiscrimination
							Vulnerability Disclosure Policy
			CONNECT WITH US
				Facebook
								Twitter
								Instagram
								LinkedIn
							Youtube
								Pinterest
								Snapchat
								Email
			LANGUAGES
				Español
							繁體中文
							Tiếng Việt
							한국어
							Tagalog
							Русский
							العربية
							Kreyòl Ayisyen
							Français
							Polski
							Português
							Italiano
							Deutsch
							日本語
							فارسی
							English


U.S. Department of Health & Human Services
			Accessibility
			External Links
			Privacy
			Policies
			No Fear Act
			FOIA
			Nondiscrimination
			OIG
			Vulnerability Disclosure Policy
			USA.gov


Exit Notification / Disclaimer Policy Close
 Links with this icon  indicate that you are leaving the CDC website. The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
				Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
				You will be subject to the destination website's privacy policy when you follow the link.
				CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Website Disclaimers
 Cancel Continue