The Registry of Toxic Effects of Chemical Substances

Isocyanic acid, methylenedi - p - phenylene ester

RTECS #: NQ9350000

CAS #: 101-68-8

UPDATE: February 2005 MW: 250.27 MF: C15H10N2O2


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. SKIN AND EYE IRRITATION DATA:
  3. MUTATION DATA:
  4. REPRODUCTIVE EFFECTS DATA:
  5. ACUTE TOXICITY DATA:
  6. OTHER MULTIPLE DOSE DATA:
  7. REVIEWS:
  8. STANDARDS AND REGULATIONS:
  9. NIOSH DOCUMENTATION AND SURVEILLANCE:
  10. STATUS IN FEDERAL AGENCIES:
  11. REFERENCES:

SYNONYMS:

  1. 1,1' - Methylenebis (4 - isocyanatobenzene)
  2. 4,4' - Diisocyanatodiphenylmethane
  3. 4,4' - Diphenylmethane diisocyanate
  4. 4,4' - Methylenebis (phenyl isocyanate)
  5. 4,4' - Methylenediphenyl diisocyanate
  6. 4,4' - Methylenediphenyl isocyanate
  7. 4,4' - Methylenediphenylene isocyanate
  8. 4 - 4' - Diisocyanate de diphenylmethane (French)
  9. Benzene, 1,1' - methylenebis (4 - isocyanato - (9CI)
  10. Bis (1,4 - isocyanatophenyl) methane
  11. Bis (4 - isocyanatophenyl) methane
  12. Bis (p - isocyanatophenyl) methane
  13. Caradate 30
  14. Desmodur 44
  15. Difenil - metan - diisocianato (Italian)
  16. Difenylmethaan - dissocyanaat (Dutch)
  17. Diphenyl methane diisocyanate
  18. Diphenylmethan - 4,4' - diisocyanat (German)
  19. Diphenylmethane 4,4' - diisocyanate
  20. Diphenylmethane diisocyanate (ACGIH:OSHA)
  21. Hylene M50
  1. Isonate
  2. Isonate 125 MF
  3. Isonate 125M
  4. MDI
  5. MDI (OSHA)
  6. Methylene bisphenyl isocyanate
  7. Methylene bisphenyl isocyanate (ACGIH:OSHA)
  8. Methylenebis (4 - isocyanatobenzene)
  9. Methylenebis (4 - phenyl isocyanate)
  10. Methylenebis (4 - phenylene isocyanate)
  11. Methylenebis (p - phenyl isocyanate)
  12. Methylenebis (p - phenylene isocyanate)
  13. Methylenedi - p - phenylene diisocyanate
  14. Methylenedi - p - phenylene isocyanate
  15. Methylenediphenyl diisocyanate
  16. NCI - C50668
  17. Nacconate 300
  18. Rubinate 44
  19. p,p' - Diphenylmethane diisocyanate
  20. p,p' - Methylenebis (phenyl isocyanate)


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
eye
rabbit 		100 mg moderate NTIS** OTS0516728
skin
rabbit 		500 mg/24 hour moderate EJTXAZ 9,41,1976


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
cytogenetic analysis human lymphocyte 540 mg/L TOLED5 36,37,1987
cytogenetic analysis human lymphocyte 0.64 mg/plate CRTXB2 31,737,2001
DNA adduct inhalation
rat 		2 mg/m3/52 week- intermittent CRNGDP 17,1069,1996
DNA adduct inhalation
rat 		0.2 mg/L/17 hour/1 year CRTXB2 31,737,2001
DNA damage inhalation
human 		20 ppb/15 minute- continuous TOLED5 60,131,1992
mutation in microorganisms Salmonella typhimurium 50 µg/plate (-enzymatic activation step) SWEHDO 6,221,1980
mutation in microorganisms Salmonella typhimurium 0.2 mg/plate (+enzymatic activation step) CRTXB2 31,737,2001
micronucleus test inhalation
rat 		7.1 mg/m3/3 hour TOSCF2 58,102,2000
sister chromatid exchange human lymphocyte 2,170 mg/L TOLED5 36,37,1987


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
rat 		lowest published toxic concentration: 9 mg/m3/6 hour (6-15 day pregnant) Reproductive: Other effects on female

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		NTIS** OTS0572542


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
human 		lowest published toxic concentration: 130 ppb/30 minute Immunological Including Allergic: Increased immune response

Nutritional and Gross Metabolic: Body temperature increase 		AIHAAP 27,121,1966
inhalation
rat 		lethal concentration (50 percent kill): 178 mg/m3 N/R AIHAAP 43,89,1982
inhalation
rat 		lowest published toxic concentration: 8 mg/m3/6 hour Lung, Thorax, or Respiration: Changes in lung weight

Lung, Thorax, or Respiration: Other changes 		ARTODN 74,257,2000
inhalation
rat 		lowest published toxic concentration: 20 mg/m3/6 hour Lung, Thorax, or Respiration: Other changes

Biochemical: Metabolism (intermediary): Lipids including transport 		ARTODN 74,257,2000
inhalation
rat 		lowest published toxic concentration: 2.4 mg/m3/6 hour Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Lung, Thorax, or Respiration: Other changes

Biochemical: Metabolism (intermediary): Other proteins 		ARTODN 74,257,2000
inhalation
rat 		lowest published toxic concentration: 0.7 mg/m3/6 hour Behavioral: Muscle contraction or spasticity

Eye: Change in extra- ocular muscles

Eye: Other eye effects 		ARTODN 74,257,2000
inhalation
rat 		lowest published toxic concentration: 10 mg/m3/6 hour Lung, Thorax, or Respiration: Other changes

Biochemical: Metabolism (intermediary): Other proteins 		JJATDK 22,371,2002
inhalation
rat 		lowest published toxic concentration: 30 mg/m3/6 hour Lung, Thorax, or Respiration: Other changes

Lung, Thorax, or Respiration: Changes in lung weight

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		JJATDK 22,371,2002
oral
mouse 		lethal dose (50 percent kill): 2,200 mg/kg N/R 85GMAT -,63,1982
oral
rat 		lethal dose (50 percent kill): 9,200 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Ataxia

Nutritional and Gross Metabolic: Body temperature decrease 		NTIS** OTS0516728


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
guinea pig 		lowest published toxic concentration: 2 mg/m3/3 hour/5 day- intermittent Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Lung, Thorax, or Respiration: Changes in lung weight 		NTIS** OTS0538162
inhalation
rat 		lowest published toxic concentration: 3 mg/m3/18 hour/90 day- intermittent Olfaction: Other olfaction effects

Lung, Thorax, or Respiration: Other changes

Blood: Other changes 		NTIS** OTS0534539
inhalation
rat 		lowest published toxic concentration: 110 mg/m3/1 hour/3 week- intermittent Olfaction: Other olfaction effects

Lung, Thorax, or Respiration: Respiratory depression

Lung, Thorax, or Respiration: Changes in lung weight 		ARTODN 75,234,2001
inhalation
rat 		lowest published toxic concentration: 6 mg/m3/6 hour/2 year- intermittent Lung, Thorax, or Respiration: Other changes

Lung, Thorax, or Respiration: Tumors 		CRTXB2 31,737,2001
inhalation
rat 		lowest published toxic concentration: 10 mg/m3/6 hour/4 week- intermittent Lung, Thorax, or Respiration: Other changes

Lung, Thorax, or Respiration: Changes in lung weight

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		JJATDK 22,371,2002
inhalation
rat 		lowest published toxic concentration: 30 mg/m3/5 day- intermittent Immunological Including Allergic: Hypersensitivity delayed (multiple organ involvement) TOXID9 72,230,2003
skin
mouse 		lowest published toxic dose: 0.9 pph/2 day- intermittent Blood: Other changes

Skin: After topical application: Cutaneous sensitization (experimental) 		TOXID9 72,101,2003


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average 0.005 ppm DTLVS* TLV/BEI,2003
International Agency for Research on Cancer (IARC) Cancer Review Human No Adequate Data IMEMDT 19,303,1979
International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMEMDT 71,1049,1999
International Agency for Research on Cancer (IARC) Cancer Review Animal No Adequate Data IMEMDT 19,303,1979
International Agency for Research on Cancer (IARC) Cancer Review Group 3 IMEMDT 71,1049,1999
TOXICOLOGY REVIEW
CRTXB2 31,737,2001
TOXICOLOGY REVIEW
TOLED5 140-141,213,2003


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Mine Safety and Health Administration (MSHA) STANDARD air-ceiling concentration 0.02 ppm (0.2 mg/m3) DTLVS* 3,170,1971
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry) ceiling concentration 0.02 ppm (0.2 mg/m3) CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction) ceiling concentration 0.02 ppm (0.2 mg/m3) CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards) ceiling concentration 0.02 ppm (0.2 mg/m3) CFRGBR 29,1915.1000,1993
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors) ceiling concentration 0.02 ppm (0.2 mg/m3) CFRGBR 41,50-204.50,1994
Occupational Exposure Limit - AUSTRIA MAK 0.005 ppm (0.05 mg/m3), Suspected Carcinogen, JAN1999
Occupational Exposure Limit - BELGIUM time-weighted average 0.005 ppm (0.051 mg/m3), short term exposure limit 0.02 ppm, JAN1993
Occupational Exposure Limit - DENMARK time-weighted average 0.005 ppm (0.05 mg/m3), JAN1999
Occupational Exposure Limit - FRANCE VME 0.01 ppm (0.1 mg/m3), VLE 0.02 ppm (0.2 mg/m3), JAN1999
Occupational Exposure Limit - GERMANY MAK 0.005 ppm (0.05 mg/m3), JAN1999
Occupational Exposure Limit - HUNGARY time-weighted average 0.05 mg/m3, short term exposure limit 0.1 mg/m3, JAN1993
Occupational Exposure Limit - JAPAN Occupational Exposure Limit 0.05 mg/m3, JAN1999
Occupational Exposure Limit - THE NETHERLANDS MAC-TGG 0.05 mg/m3, 2003
Occupational Exposure Limit - THE PHILIPPINES time-weighted average 0.02 ppm (0.2 mg/m3), JAN1993
Occupational Exposure Limit - POLAND MAC(time-weighted average) 0.05 mg/m3, MAC( continuous) 0.2 mg/m3, JAN1999
Occupational Exposure Limit - RUSSIA short term exposure limit 0.5 mg/m3, Skin, JAN1993
Occupational Exposure Limit - SWEDEN NGV 0.005 ppm , TGV 0.01 ppm, JAN1999
Occupational Exposure Limit - SWITZERLAND MAK- week 5 ppm (15 mg/m3), short term exposure limit 25 ppm (75 mg/m3), JAN1999
Occupational Exposure Limit - THAILAND time-weighted average 0.02 ppm (0.2 mg/m3), JAN1993
Occupational Exposure Limit - UNITED KINGDOM time-weighted average 0.02 mg(NCO)/m3, short term exposure limit 0.07 mg(NCO)/m3, SEP2000
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN, KOREA American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

time-weighted average 0.005 ppm
Occupational Exposure Limit IN NEW ZEALAND, SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
time-weighted average 0.005 ppm


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO MDI-air 10 hour time-weighted average 0.005 ppm;
ceiling concentration 0.02 ppm/10 minute 		NIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 27780;
Number of Industries 41;
Total Number of Facilities 2,896;
Number of Occupations 48;
Total Number of Employees Exposed 53,321;
Total Number of Female Employees Exposed 13,421


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used in the production of polyurethane coatings, elastomers, and thermoplastic resins
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA Section 8(e) Risk Notification, 8EHQ-0892-9111
On EPA IRIS database
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NIOSH Analytical Method, 1994: Isocyanates, monomeric, 5521
NIOSH Analytical Method, 1996: Isocyanates, 5522
OSHA ANALYTICAL METHOD #33
OSHA ANALYTICAL METHOD #47


REFERENCES:

CODEN
REFERENCE
85GMAT "Toxicometric Parameters of Industrial Toxic Chemicals Under Single Exposure," Izmerov, N.F., et al., Moscow, Centre of International Projects, GKNT, 1982
AIHAAP American Industrial Hygiene Association Journal. (AIHA, 475 Wolf Ledges Pkwy., Akron, OH 44311) V.19- 1958-
ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974-
CFRGBR Code of Federal Regulations. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402)
CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971-
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
EJTXAZ European Journal of Toxicology and Environmental Hygiene. (Paris, France) V.7-9, 1974-76. For publisher information, see TOERD9.
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
JJATDK JAT, Journal of Applied Toxicology. (John Wiley & Sons Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK) V.1- 1981-
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
SWEHDO Scandinavian Journal of Work, Environment and Health. (Haartmaninkatu 1, SF-00290 Helsinki, 29, Finland) V.1- 1975-
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TOSCF2 Toxicological Sciences (Oxford University Press, 6277 Sea Harbor Drive, Orlando, FL 32887 ) V. 41, Jan. 1998-
TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981-

Used in the production of polyurethane coatings, elastomers, and thermoplastic resins

RTECS Compound Description:
   Tumorigen
   Mutagen
   Reproductive Effector
   Human Data
   Primary Irritant

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