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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 749
CCOHS Chemical Name: Michler's ketone

Synonyms:
4,4'-Bis(dimethylamino)benzophenone
Bis(4-(dimethylamino)phenyl)methanone
Bis(p-(N,N-dimethylamino)phenyl) ketone
4,4'-Bis(N,N-dimethylamino)benzophenone
p,p'-Michler's ketone
Tetramethyldiaminobenzophenone
N,N,N',N'-Tetramethyl-4,4'-diaminobenzophenone
Bis(dimethylamino)-4,4'benzophenone

CAS Registry Number: 90-94-8
RTECS Number(s): DJ0250000
EU EINECS/ELINCS Number: 202-027-5
Chemical Family: Substituted aromatic ketone / substituted diaryl ketone / substituted benzophenone / amine substituted benzophenone / bisaminophenyl ketone
Molecular Formula: C17-H20-N2-O
Structural Formula: (CH3)2-N-C6H4-C(=O)-C6H4-N-(CH3)2

SECTION 2. DESCRIPTION

Appearance and Odour:
White to greenish leaflets (19); or blue powder (21)

Odour Threshold:
Not available

Warning Properties:
Information not available for evaluation.

Uses and Occurrences:
Used mainly as a chemical intermediate in the synthesis of dyes and pigments, especially auramine derivatives, used to dye paper, textiles and leather and as dyes for printing inks; used in photosensitizer formulations.(1,19)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
White to greenish leaflets or blue powder. Can burn if strongly heated. Can decompose at high temperatures forming irritating/toxic nitrogen oxides. POSSIBLE CANCER HAZARD - may cause cancer based on animal data. POSSIBLE MUTAGEN - may cause genetic damage, based on animal data.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
There is no human or animal information available. Michler's ketone is not expected to produce significant health effects or warning signs upon short-term exposure. However, Michler's ketone is a suspected carcinogen. See Carcinogenicity below for information.

Skin Contact:
There is no human or animal information available. Michler's ketone is probably not irritating to the skin. However, it is a suspected carcinogen. See Carcinogenicity below for information.

Eye Contact:
There is no human or animal information available. Michler's ketone is not expected to cause eye irritation except as a "foreign body". Some tearing, blinking and mild temporary pain may occur as the solid material is rinsed from the eye by tears.

Ingestion:
There is no human information available. Accidental ingestion would probably not result in any health effects. Repeated ingestion has caused cancer and death in animals. Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

There is no human information available. Long-term ingestion of Michler's ketone has caused cancer and death in animals.

Carcinogenicity:

There is no human information available. The U.S. National Toxicology Program (NTP) identifies Michler's ketone as reasonably anticipated to be carcinogenic based on evidence of the carcinogenicity in experimental animals.(1)

The International Agency for Research on Cancer (IARC) has not evaluated the carcinogenicity of this chemical.

The American Conference of Governmental Industrial Hygienists (ACGIH) has no listing for this chemical.

The US National Toxicology Program (NTP) has listed this chemical as reasonably anticipated to be a human carcinogen.

Teratogenicity and Embryotoxicity:
There is no human or animal information available.

Reproductive Toxicity:
There is no human or animal information available.

Mutagenicity:
There are no reports of mutagenicity in humans or human cell cultures. Michler's ketone is mutagenic in somatic cells following oral exposure of live animals.

Toxicologically Synergistic Materials:
No information is available.

Potential for Accumulation:
No information is available.


SECTION 4. FIRST AID MEASURES

Inhalation:
This chemical is a possible cancer and mutagenicity hazard. Take proper precautions to ensure your own safety before offering first aid (e.g. wear appropriate personal protective equipment). No immediate health effects expected. Remove source of contamination or move victim to fresh air and obtain medical advice.

Skin Contact:
Avoid direct contact. Wear chemical protective clothing, if necessary. Quickly and gently blot or brush away excess chemical. Wash gently and thoroughly with water and non-abrasive soap for at least 5 minutes or until the chemical is removed. Under running water, remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
Avoid direct contact. Wear chemical protective clothing, if necessary. Quickly and gently blot or brush away excess chemical. Do not allow victim to rub eye(s). Let the eye(s) water naturally for a few minutes. Have victim look right and left, and then up and down. If particle/dust does not dislodge, flush with lukewarm, gently flowing water for 5 minutes or until particle/dust is removed, while holding the eyelid(s) open. If irritation persists, obtain medical attention. DO NOT attempt to manually remove anything stuck to the eye(s)

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, or is unconscious or convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. Have victim drink 240 to 300 mL (8 to 10 oz.) of water to dilute material in the stomach. Obtain medical attention immediately.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest). Consult a doctor and/or the nearest Poison Control Centre in the event of any exposure. All first aid procedures should be periodically reviewed by a doctor familiar with the material and its condition of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
220 deg C (428 deg F) (method not specified) (22)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not available

Upper Flammable (Explosive) Limit (UFL/UEL):
Not available

Autoignition (Ignition) Temperature:
480 deg C (896 deg F) (22)

Sensitivity to Mechanical Impact:
Probably not sensitive. Normally stable compound.

Sensitivity to Static Charge:
Not applicable. Solid.

Combustion and Thermal Decomposition Products:
Nitrogen oxides.(21)

Fire Hazard Summary:
Michler's ketone can burn if strongly heated. During a fire, irritating/toxic nitrogen oxides may be generated.

Extinguishing Media:
Carbon dioxide, dry chemical powder, alcohol foam, polymer foam, water spray or fog.(21)

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind to avoid toxic decomposition products.
Water or foam may cause frothing. The frothing may be violent and could endanger personnel close to the fire. However, a water spray or fog that is carefully applied to the surface of the material, preferably with a fine spray or fog nozzle, will cause frothing that will blanket and extinguish the fire. In addition, water spray or fog can be used to absorb heat, keep containers cool and protect exposed material. If a leak or spill has not ignited, use water spray to disperse the vapours and protect personnel attempting to stop a leak. Water spray may be used to flush spills away from ignition sources. Solid streams of water may be ineffective and spread material.
Michler's ketone and its thermal decomposition products are hazardous to health. Do not enter without wearing specialized protective equipment suitable for the situation. Firefighter's normal protective equipment (Bunker Gear) will not provide adequate protection. Chemical resistant clothing (e.g. chemical splash suit and positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Comments:
NFPA has no listing for this chemical in Codes 49 or 325.


SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 268.36

Conversion Factor:
1 ppm = 10.95 mg/m3; 1 mg/m3 = 0.091 ppm at 25 deg C (calculated)

Physical State: Solid
Melting Point: 172 deg C (342 deg F) (20); 174-176 deg C (345-349 deg F) (21)
Boiling Point: Greater than 360 deg C (680 deg F) (decomposes) (19,20)
Relative Density (Specific Gravity): Not available
Solubility in Water: Practically insoluble (1,20)
Solubility in Other Liquids: Soluble in ethanol, warm benzene and pyrimidine; very slightly soluble in diethyl ether (1,20)
Coefficient of Oil/Water Distribution (Partition Coefficient): Not available
pH Value: Not available
Vapour Density: Not available
Vapour Pressure: Not available
Saturation Vapour Concentration: Not available
Evaporation Rate: Not available
Critical Temperature: Not available

SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable

Hazardous Polymerization:
Does not occur

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


STRONG OXIDIZING AGENTS (e.g. hydrogen peroxide, perchloric acid) - risk of fire and explosion.(21)
STRONG REDUCING AGENTS - vigorous or violent reaction.(21)

Hazardous Decomposition Products:
None reported

Conditions to Avoid:
Temperatures above 220 deg C, generation of dust

Corrosivity to Metals:
Information not available.


SECTION 11. TOXICOLOGICAL INFORMATION

There are no standard animal toxicity values available.

Effects of Short-Term (Acute) Exposure:

Ingestion:
No deaths were observed in female rats administered 50 mg/kg or 150 mg/kg at 21 and 4 hours prior to sacrifice, respectively.(2)

Effects of Long-Term (Chronic) Exposure:

Ingestion:
Rats were administered up to 1627 mg/kg/day in the diet for 4 weeks. Complete lethality occurred at the high dose (1466 mg/kg/day for males; 1627 mg/kg/day for females). At 680 mg/kg/day, 3/5 males and at 755 mg/kg/day, 5/5 females died. At 350 mg/kg/day, 2/5 females died. No deaths were observed at lower doses. Mice were administered up to 2317 mg/kg/day Michler's ketone in the diet for 4 weeks. At 2085 mg/kg/day, 1/5 males and at 2317 mg/kg/day, 1/5 females died. No deaths were observed at the lower doses.(3)

Carcinogenicity:
The National Cancer Institute (NCI) has concluded that there is sufficient evidence for the carcinogenicity of Michler's ketone in animals. Rats and mice were administered Michler's ketone in the diet for 78 weeks. Male rats were fed 250 or 500 ppm (approx. 25 or 50 mg/kg/day), female rats 500 or 1000 ppm (approx. 55 or 110 mg/kg/day) and mice 1250 or 2500 ppm (approx. 188 or 375 mg/kg/day for male mice and 208 or 417 mg/kg/day for female mice). A distinct dose-related body weight depression in female rats and in mice of both sexes was observed. A significant increase in mortality was also observed in high dose animals. Liver (hepatocellular) cancer was observed in rats and female mice, and cancer of the circulatory system, skin and subcutaneous tissue was observed in male mice. Observations were statistically significant for both sexes of both species at the high dose and for females of both species at the low dose.(3)

Mutagenicity:
Michler's ketone is mutagenic in mammalian somatic cells, in vivo following oral exposure.(2,6,13)
Michler's ketone is mutagenic in mammalian somatic cells in vitro.(4,8,9,11,13,15,16,17) Positive results have also been obtained in bacteria with and/or without metabolic activation.(5,7,12,13)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Report on Carcinogens. 11th ed. US Department of Health and Human Services, Public Health Service, National Toxicology Program
(2) Kitchin, K.T., et al. Predictive assay for rodent carcinogenicity using in vivo biochemical parameters: operational characteristics and complementarity. Mutation Research. Vol. 166 (1992). p. 253-272
(3) National Cancer Institute. Bioassay of Michler's ketone for possible carcinogenicity: CAS No. 90-94-8. National Cancer Institute Carcinogenesis Technical Report Series No. 181. (NCI-CG-TR-181). U.S. Department of Health, Education, and Welfare, 1979.
(4) Caspary, W.J., et al. Evaluation of the L5178Y mouse lymphoma cell mutagenesis assay: interlaboratory reproducibility and assessment. Environmental and Molecular Mutagenesis. Vol. 12, suppl. 13 (1988). p. 195- 229
(5) Dunkel, V.C., et al. Reproducibility of microbial mutagenicity assays: II. Testing of carcinogens and noncarcinogens in Salmonella typhimurium and Escherichia coli. Environmental Mutagenesis. Vol. 7, suppl. 5 (1985). p. 1- 248
(6) Mirsalis, J.C., et al. Measurement of unscheduled DNA synthesis and S- phase synthesis in rodent hepatocytes following in vivo treatment: testing of 24 compounds. Environmental and Molecular Mutagenesis. Vol. 14, no. 3 (1989). p. 155-164
(7) Zeiger, E., et al. Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals. Environmental and Molecular Mutagenesis. Vol. 19, suppl. 21 (1992). p. 2-141
(8) Myhr, B.C., et al. Evaluation of the L5178Y mouse lymphoma cell mutagenesis assay: intralaboratory results for sixty-three coded chemicals tested at Litton Bionetics, Inc. Environmental and Molecular Mutagenesis. Vol. 12, suppl. 13 (1988). p. 103-194
(9) Lafi, A., et al. The effect of Michler's ketone on cell division, chromosome number and structure in cultured Chinese hamster cells. Mutagenesis. Vol. 1, no. 1 (1986). p. 17-20
(10) Vecchio, D., et al. DNA fragmentation and sister chromatid exchanges induced by commercial Auramine O, purified Auramine, and Michler's ketone. Nato ASI Series A: Life Sciences. Vol. 60 (1983). p. 745-754
(11) Williams, G.M., et al. Reliability of the hepatocyte primary culture/DNA repair test in testing of coded carcinogens and noncarcinogens. Mutation Research. Vol. 97 (1982). p. 359-370
(12) Rossman, T.G., et al. Performance of 133 compounds in the lambda prophage induction endpoint of the microscreen assay and a comparison with S. typhimurium mutagenicity and rodent carcinogenicity assays. Mutation Research. Vol. 260, no. 4 (August, 1991). p. 349-367
(13) Tennant, R.W., et al. Comparison of multiple parameters of rodent carcinogenicity and in vitro genetic toxicity. Environmental Mutagenesis. Vol. 8 (1986). p. 205-227
(14) Scribner, J.D., et al. Binding of the dye intermediates Michler's ketone and methane base to rat liver nucleic acids and lack of mutagenicity in Salmonella typhimurium. Cancer Letters. Vol. 9 (1980). p. 117-121
(15) Dunkel, V.C., et al. Interlaboratory evaluation of the C3H/10T1/2 cell transformation assay. Environmental and Molecular Mutagenesis. Vol. 12, no. 1 (1988). p. 21-31
(16) Kumaroo, P.V., et al. In vitro chromosome aberration and sister chromatid exchange tests on 35 chemicals in Chinese hamster ovary cells. 1992 EMS Abstracts. Environmental Mutagenesis. p. 32
(17) Traul, K.A., et al. A rapid in vitro assay for carcinogenicity of chemical substances in mammalian cells utilizing an attachment-independence endpoint: 2. Assay validation. Journal of Applied Toxicology. Vol. 1, no. 3 (1981). p. 190-195
(18) Emmett, E.A., et al. Phototoxicity occurring during the manufacture of ultraviolet-cured ink. Archives of Dermatology. Vol. 113 (June, 1977). p. 770-775
(19) Keith, L.H., et al., eds. Compendium of safety data sheets for research and industrial chemicals. Part V. VCH Publishers, 1985. p. 2406
(20) The Merck index: an encyclopedia of chemicals, drugs, and biologicals. 11th edition. Merck and Co., Inc., p. 972
(21) The Sigma-Aldrich library of chemical safety data. Edition II. Volume 1. Sigma-Aldrich Corporation, 1988. p. 430B
(22) MSDS database record for Michler's ketone (BASF Canada Inc.). Date of MSDS: 1995-03-03
(23) European Communities (EC). Commission Directive 2004/73/EC. Apr. 29, 2004
(24) National Institute for Occupational Safety and Health (NIOSH). Ketones I. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113. Aug. 1994. Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>

Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 1996-06-10

Revision Indicators:
Engineering controls 1996-12-01
Exposure controls 1996-12-01
Storage 1996-12-01
Handling 1996-12-01
WHMIS (detailed class) 1997-07-01
Bibliography 2005-02-02
Bibliography 2005-03-05
Sampling/analysis 2005-03-05



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