Tobacco Smoke Toxicity

by Chris Lanham

Tobacco Smoke

Formation processCombustion

Tobacco and paperPollutants emitted

Particulate matter

Particulate Matter

Smoke and gas particlesPM2.5

Extremely small25,000 = 1 inch14 mg per 0.9 g cigarette

Types of Cigarette Smoke

Mainstream (Primary)Secondhand (Secondary)

Pollutants in Tobacco Smoke

4,000 Chemical byproducts172 known toxins

67 known carcinogens

Figure 1.1 – Some common, dangerous chemicals found in cigarette smoke

Pollutants in Secondhand 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)

Groupings

Observation

CessationMoribund20 % survival in group

SacrificingGross lesions and organ samples collected

Examined microscopically

Tumor Formation

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

Sample Analysis

Cotinine measured10 ng/mL cut-off

Indicates high exposure to ETS

Sample Analysis

Urine sample centrifugedHPLC used to measure NNK metabolites

Results

Cotinine/metabolite relationship

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

Resources

http://tobaccosmoke.org/book/export/html/4“Dose-Response Study of the Carcinogenicity of Tobacco-Specific N-Nitrosamines in F344 Rats”“Metabolites of a Tobacco-specific Lung Carcinogen in the Urine of Elementary School-aged Children.”