Particulate Matter
Smoke and gas particlesPM2.5
Extremely small25,000 = 1 inch14 mg per 0.9 g cigarette
Pollutants in Tobacco Smoke
4,000 Chemical byproducts172 known toxins
67 known carcinogens
Figure 1.1 – Some common, dangerous chemicals found in cigarette smoke
Carcinogenicity of NNK in Rats
NNK4-(methylnitrosamino)-1-(3-pyridyl)-1-butanoneTobacco-specific nitrosamine (TSNA)Among the most important carcinogens
Observe dose-response for carcinogenicity3 TSNAs
NNK, NNN, NAT
Experimental Preparation
Synthesize 30 g of each TSNAUsed HPLC to ensure purity
Purchase 6-week-old male/female ratsPlaced in groups of three inside each cageGiven Purina chow and waterRat weight recorded weekly
Injection
9 weeks-oldSubcutaneous injection3 injections/week for 20 weeks
3 doses9.0 mmol/kg body weight (high)3.0 mmol/kg body weight (medium)1.0 mmol/kg body weight (low)
Observation
CessationMoribund20 % survival in group
SacrificingGross lesions and organ samples collected
Examined microscopically
Important Findings
NNK carcinogenicityRespiratory tract tumorsLowest dose (1.0 mmol/kg)High occurrence of lung tumors
85 % in males
NNK Metabolites in School Children
Background studiesETS and lung cancer
~20 % increaseSeveral major agencies
US HHSNRCUS EPA
Investigate amount of lung carcinogen NNKQuantified by two metabolites
Sample Selection
Minneapolis school childrenPublic elementary schoolsCaregiver asked 2 main questions
Packs of cigarettes/month# of smokers in house
> 1 answer considered exposureSeveral other questions
Indicate outside exposureUrine samples obtained at school
Provided organic fruit juices
Results
Positive for carcinogen metabolites96 % students > 5 ng/mL cotinine 50 % students < 5 ng/mL cotinine
Significant uptake of NNK
Conclusion
Tobacco smoke extremely toxicHigh amount of carcinogens
NNK potent carcinogenMouse studies reveal danger
Significant amount of NNK in exposed childrenStill present in “unexposed” category
Relationship uncertaintyFuture studies
Safety perspective
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