Methodologies for the quantitative estimation of toxicant dose to cigarette smokers using physical, chemical and bioanalytical data

Figures & data

Figure 1. Risk assessment paradigm for inhalation exposure to ambient particles (adapted from NRC, 1998).

Figure 2. Disposition of smoke constituents from smoking article through the human body.

Table 1. Solanesol retention for studies with controlled inhalation volume and breath-hold times.

Inhalation volume (mL)	Breath-hold time (s)	No. of products	No. of studies	Mean RR (%)	Calculated RR (%)^a
75	2	44	5	53	53
150	2	4	1	53	55
250	2	14	2	54	57
500	0	10	1	52	56
500	2	44	5	67	63
500	10	10	1	88	89
1000	2	14	2	71	74

^aCalculated from multiple regression Equation (3).

RR = respiratory retention.

Figure 3. Respiratory retention versus log (vapor pressure). Individual data points shown as open diamonds. Solid squared are averages grouped by log(VP) rounded to an integer. The circled data are for solanesol.

Table 2. Calculated respiratory retention for compounds used to estimate dose.

Compound	Vapor pressure (Pa)	Calculated retention (%)	Measured retention (%); mean (SD)
Formaldehyde	507 022	98.6	97.7 (1.6) a
Acetaldehyde	119 530	98.0	96.3 (1.4)^a, >99^b
Propionaldehyde	42 250	97.5	98.0 (1.8)^a
Acrolein	36 444	97.5	99.7 (0.7)^a
Acetone	30 404	97.4	92.6 (3.0)^a
Butyraldehyde	14 847	97.1	98.7 (2.3)^a
Methyl ethyl ketone	12 702	97.0	95.1 (3.1)^a
Crotonaldehyde	4105	96.5	98.0 (3.0)^a
NAB	0.0042	90.5	NA
NAT	0.0033	90.4	NA
NNN	0.0028	90.3	84/97 (10/3)^b
Pyrene	0.00033	89.4	92.9 (7.9)^c
NNK	0.00013	89.0	63/84 (12/7)^b

^aMoldoveanu et al. (2007). 15 subjects and 2 cigarettes.

^bFeng et al. (2007). 16 subjects.

^cMoldoveanu et al. (2008a). 10 subjects.

Two inhalation patterns, SD. estimated from Figure 6.

SD = standard deviation; NA = measured data not available.

Figure 4. Histogram of estimated mouth-spill from subjects in Canadian and German clinical studies.

Table 3. Mouth-spill calculated by two methods for subjects in two clinical studies. Two replicates for 139 subjects in each study.

	Both^a (%)	CA^a (%)	DE^a (%)	Both^b (%)	CA^b (%)	DE^b (%)
Average	31.8	34.4	29.2	33.4	35.1	31.8
SD	19.8	15.9	22.8	20.6	17.0	23.5
Range	−40 to 96	−8 to 85	−40 to 94	−31 to 96	−31 to 86	−28 to 96
5th%	0.4	8.5	−2.7	−2.0	7.9	−8.4
10th%	7.2	15.6	1.9	8.1	16.1	2.8
25th%	18.7	23.1	13.1	20.7	25.0	16.4
50th%	31.7	33.0	28.4	33.6	34.9	31.7
75th%	44.4	44.6	43.5	46.6	46.8	46.4
90th%	57.7	52.4	60.7	59.3	54.6	64.2
95th%	63.4	60.7	64.9	66.7	61.1	68.6

^aCalculated from the average of 2 days MLE and second day TNE.

^bCalculated from second day MLE and second day TNE.

CA = Canada, DE = Germany, SD = standard deviation.

Figure 5. Carbonyl mouth level exposure (a) and dose (b) for the German clinical study.

Figure 6. Tobacco-specific nitrosamine and pyrene mouth level exposure (a) and dose (b) for the German clinical study.

Figure 7. Carbonyl and pyrene mouth level exposure (a) and dose (b) for the Canadian clinical study.

Figure 8. Correlation of urinary HPMA (expressed as acrolein equivalents) with acrolein MLE (a) and Dose (b).

Figure 9. Correlation of urinary 1-hydroxypyrene (expressed as pyrene equivalents) with pyrene MLE (a) and Dose (b).

Figure 10. Correlation of urinary total NNAL (NNAL + glucuronide expressed as pyrene equivalents) with pyrene MLE (a) and Dose (b).

Moldoveanu SC, Coleman W 3rd, Wilkins J. (2007). Determination of carbonyl compounds in exhaled cigarette smoke. Beitr Tabakforsch Int 22:346–57

 Google Scholar

Feng S, Plunkett SE, Lan K, et al. (2007). A new method for estimating the retention of selected smoke constituents in the respiratory tract of smokers during cigarette smoking. Inhal Toxicol 19:169–79

 PubMed Web of Science ®Google Scholar

Moldoveanu SC, Coleman W 3rd, Wilkins JM. (2008a). Determination of polycyclic aromatic hydrocarbons in exhaled cigarette smoke. Beitr Tabakforsch Int 23:85–97

 Google Scholar