PARA- CYMENE
Prepared by Philip Morris USA for Submission to ANVISA
Page I of 3
CAS No 99-87-6
Toxicity Data on The following information was generated from the
Hazardous Substances Databank (HSDB),
Un-burned a database of the National Library of Medicine's TOXNET system
Material {http://toxnet.nlm.nih.gov) on January 21, 2002.
ANIMAL TOXICITY STUDIES:
NON-HUMAN TOXICITY EXCERPTS:
DOGS TOLERATED DOSES OF 2 G DAILY WITH DIARRHEA AS ONLY ADVERSE EFFECT.
... BY SC INJECTION OF RABBITS WITH 2 ML ... DAILY ... OBSERVED ...
INITIAL SLIGHT FALL FOLLOWED BY INCR/WHITE CELLS/; RED CELLS &
HEMOGLOBIN SHOWED IRREGULAR CHANGES WITH TENDENCY TO FALL. [Browning, E.
Toxicity and Metabolism of Industrial Solvents. New York: American
Elsevier, 1965.105]**PEER REVIEWED**
... IN BLOOD /PUNCTURE/ OF RABBITS ... RAPID APPEARANCE OF IMMATURE WHITE
CELLS ... FOLLOWED BY BLUE COLORATION OF CYTOPLASM OF PRACTICALLY ALL
NEUTROPHILS WITH GRANULATIONS WHICH GAVE THEM APPEARANCE SIMILAR TO THOSE
SEEN IN HUMAN MYELOID LEUKEMIA. ... STEADY RISE OF LEUKOCYTES ... /SC
INJECTION, 2 ML DAILY/. [Browning, E. Toxicity and Metabolism of
Industrial Solvents. New York: American Elsevier, 1965.105]**PEER
REVIEWED**
NON-HUMAN TOXICITY VALUES:
LD50 Rat oral 4750 mg/kg [Budavari, S. (ed.). The Merck index - An
Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ:
Merck and Co., Inc., 1996. 467]**PEER REVIEWED**
Toxicity Data on Data on the toxicity of PARA- CYMENE after combustion has been evaluated in a series of studies. The results
of these studies may be found in the following references:
Burned Material
E.L. Carmines, 2002, "Evaluation of the Potential Effects of Ingredients Added to Cigarettes. Part I: Cigarette
Design, Testing Approach and Review of Results" Food and Chemical Toxicology, 40:77-91. **PEER
REVIEWED**
K. Rustemeier et al, 2002 "Evaluation of the Potential Effects of Ingredients Added to Cigarettes Part II.
Chemical Smoke Composition" Food and Chemical Toxicology, 40:93 -104. "PEER REVIEWED**
Roemer et al., 2002" Evaluation of the Potential Effects of Flavor Ingredients Added to Cigarettes. Part 3. In
Vitro Genotoxicity and Cytotoxicity" Food and Chemical Toxicology, 40:105-111. **PEER REVIEWED**
P.M. Vanscheeuwijck et al, 2002" Toxicological Evaluation of Cigarettes without and with the Addition of Flavor
Ingredients to the Tobacco. Part 4. Subchronic Inhalation Toxicity" Food and Chemical Toxicology, 40:113-131,
**PEER REVIEWED**
These studies indicate that chemicals used in the production of cigarettes do not increase the overall toxicity of
cigarette smoke.
Data on the ^ n e overwhelming medical and scientific consensus is that cigarette smoking causes lung cancer, heart
„ f f disease, emphysema and other serious diseases in smokers. Smokers are far more likely to develop serious
•EJJec*s on diseases, like lung cancer, than non-smokers. There is no "safe" cigarette. Philip Morris has not conducted
Human Health human studies of the health effects of ingredients used in cigarette manufacture. Government health warnings
about smoking apply to all cigarettes, regardless of the ingredients added, including those containing only
tobacco and paper.
While Philip Morris has not conducted human studies on the health effects of ingredients used in cigarette
manufacture, studies have been conducted using scientifically accepted in vitro and in vivo toxicity assays with
various ingredient mixtures (see Toxicity Data on Burned Material above). These studies show there is no
meaningful difference in the composition or toxicity of smoke when the smoke from cigarettes with added
ingredients is compared to the smoke from cigarettes without added ingredients. These findings are supported
by similar studies from the published literature. It is our scientific judgment, based on the best available data,
http://legacy.library.ucsf.edu/tid/dik80g00/pdf
PARA- CYMENE
Prepared by Philip Morris USA for Submission to ANVISA
Page 2 of 3
that the ingredients used in our cigarettes do not increase the overall toxicity of cigarette smoke.
Furthermore, the ingredients added to tobacco have been reviewed by group of six renowned scientists and
they have concluded that the ingredients added to tobacco in the manufacture of cigarettes are net hazardous
under the conditions of use (Doull et al, 1994,1998). A second independent safety assessment was performed
by Vettorazzi and Frawley in 1997. They concluded that cigarette ingredients are not harmful under the
conditions of use.
Doull, J; Frawley, JP; George, WJ; Loomis, TA; Squire, RA; Taylor, SL. A safety assessment of ingredients
added to tobacco in the manufacturing of cigarettes. Covington and Burling, Washington, DC, 1994.
Doull, J; Frawley, JP; George, WJ; Loomis, TA; Squire, RA; Taylor, SL. A safety assessment of ingredients
added to tobacco in the manufacturing of cigarettes. Covington and Burling, Washington, DC, February, 1998.
Vettorazzi, G and Frawley, JP. A safety assessment of ingredients added to tobacco in the manufacturing of
cigarettes made or sold in Chile. Covington and Burling, Washington, DC, September, 1997.
The following information was generated from the
Hazardous Substances Databank (HSDB),
a database of the National Library of Medicine's TOXNET system
(http://toxnet.nIm.nih.gov) on January 21, 2002.
HUMAN HEALTH EFFECTS:
HUMAN TOXICITY EXCERPTS:
EXTENSIVE CHEMICAL PNEUMONITIS MAY BE CAUSED BY ASPIRATION INTO LUNGS OF
SMALL AMT OF LIQUID CYMENE, OWING TO ITS LOW SURFACE TENSION & LOW
VISCOSITY. [Browning, E. Toxicity and Metabolism of Industrial Solvents.
New York: American Elsevier, 1965.106]**PEER REVIEWED**
... PRIMARY SKIN IRRITANT WHICH BY CONTACT WITH LIQUID CAN DEVELOP
ERYTHEMA, DRYNESS & DEFATTING, INTENSITY DEPENDING ON DOSE Samp;
DURATION OF CONTACT. [Browning, E. Toxicity and Metabolism of Industrial
Solvents. New York: American Elsevier, 1965.105]**PEER REVIEWED**
P-CYMENE ... WHEN GIVEN BY MOUTH CAUSES HEADACHE, NAUSEA & VOMITING.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York:
American Elsevier, 1965.104]**PEER REVIEWED**
VAPOR (GAS) IRRITANT CHARACTERISTICS: VAPORS ARE NONIRRITATING TO EYES AND
THROAT. LIQUID OR SOLID IRRITANT CHARACTERISTICS: MINIMUM HAZARD. IF
SPILLED ON CLOTHING AND ALLOWED TO REMAIN, MAY CAUSE SMARTING AND
REDDENING OF THE SKIN. LIQUID: IRRITATING TO ... EYES. [U.S. Coast Guard,
Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II.
Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER
REVIEWED**
SKIN, EYE AND RESPIRATORY IRRITATIONS:
VAPOR (GAS) IRRITANT CHARACTERISTICS: VAPORS ARE NONIRRITATING TO EYES AND
THROAT. LIQUID OR SOLID IRRITANT CHARACTERISTICS: MINIMUM HAZARD. IF
SPILLED ON CLOTHING AND ALLOWED TO REMAIN, MAY CAUSE SMARTING AND
REDDENING OF THE SKIN. [U.S. Coast Guard, Department of Transportation.
CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S.
Government Printing Office, 1984-5.]**PEER REVIEWED**
LIQUID /IS/ IRRITATING TO ... EYES. [U.S. Coast Guard, Department of
Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington,
D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**
PROBABLE ROUTES OF HUMAN EXPOSURE:
Occupational exposure to p-cymene occurs through dermal contact and
inhalation of vapor(1); p-cymene is a primary skin irritant; contact with
the liquid can cause dryness, defatting and erythema(1). The general O
population is exposed to p-cymene through inhalation and oral consumption o>
of foods which contain p-cymene as a natural constituent(SRC). [(1)
Parmeggiani L; Encyl Occup Health & Safety 3rd ed Geneva, Switzerland:
-A
International Labour Office p. 1074-5 {1983)]**PEER REVIEWED**
NIOSH (NOES Survey 1981-1983) has statistically estimated that 74,141 -a. .
workers (12,723 of these are female) are potentially exposed to p-cymene CO
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PARA- CYMENE
Prepared by Philip Morris USA for Submission to ANVISA
Page 3 of 3
in the US(1). Occupational exposure to p-cymene may occur through
inhalation and dermal contact with this compound at workplaces where
p-cymene is produced or used(SRC). Air samples collected inside a tire
re-treading factory in Italy contained p-cymene levels of 1-450 ug/cu
m(2). The general population may be exposed to p-cymene through the
ingestion of food products or dermal contact with plants and vegetation
that contain this compound and may also be exposed dermaliy to p-cymene
through the use of fragrance products that contain this compound(SRC).
[(1) NIOSH; National Occupational Exposure Survey (NOES) (1983) (2) Cocheo
V et al; Amer Ind Hyg Assoc J 44: 521-7 (1983)]**PEER REVIEWED**
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