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The nicotine-based yield of another C4-carbonyl constituent, i. This effect was not seen under HCI conditions. A numerical increase in 2-butanone yields of the same magnitude nicotine-based, independent of the sugar application level was also seen in the smoke generated from research cigarettes with ingredient mixtures containing sugars at application levels of up to In a study using uniformly 14 C-labeled glucose and sucrose as ingredients, less than 0.

The most important parameter for the yield of both constituents is the overall smoke yield of a cigarette, as demonstrated by the tight correlation of acrolein yields with those of tar or carbon monoxide in various series of commercial cigarettes data from Gregg et al. If tested under HCI conditions, there was no sugar-related effect observed for either of these two constituents but there was for styrene, a constituent with similar chemical structure.

The observations in the first ingredient mixture study may simply be due to the replacement of nicotine-containing tobacco with the ingredient mixture, thus lowering the normalization basis for the specific constituent yields, because these effects were absent if yields were related to tar. Such effects may of course also be related to other components of the ingredient mixtures than sugars. Again, the yield of these two smoke constituents correlated well with tar or carbon monoxide yields in the smoke of commercial cigarettes data from Gregg et al.

Although it may be conceivable that benzene could be formed from the C6 structure of mono-saccharides, less than 0. This was not observed under HCI conditions. The increased yield seen for some carbonyl constituents may be related to the decreased yields for some nitrogen-containing mainstream smoke constituents, because some carbonyl compounds may trap nitrogen-containing precursors of these constituents. No effect was found for N-nitrosonornicotine, if smoke was generated under HCI conditions. Interestingly, there is no trend for the NNK yields nicotine-based , which might be explainable by the higher proportion of NNK preformed in the tobacco versus its formation during smoking in comparison to N-nitrosonornicotine Moldoveanu and Borger Ding, There were clearly two distinct classes of yields for the tobacco-specific N-nitrosamines Figure 3E.

This may be related to diverging analytical methodologies but may also reflect different generations of research cigarettes with lowered preformed contents of tobacco-specific N-nitrosamines in the tobacco of more recent productions Boyette and Hamm, Decreases for the nicotine-based yields of both N-nitrosonornicotine and NNK were found in the smoke of the research cigarettes with sugar-containing mixtures Rustemeier et al.

In another ingredient mixture study, N-nitrosonornicotine yields were more decreased than NNK yields Baker et al. For commercial cigarettes, there is a categorical difference between American-blend and Virginia-type cigarettes due to the higher nicotine content in Burley tobacco, and the yields of the tobacco-specific N-nitrosamines in general correlate less with those of other constituents data from Gregg et al.

The nicotine-based yields of several aromatic amines decreased with increasing sugar application levels, an effect which was statistically significant for 4-aminobiphenyl Table 3 , Figure 3F. This is in line with the above-mentioned scavenging of nitrogen-containing intermediates by carbonyls, which are formed in slightly increased amounts during the pyrolysis of the sugars. The effect was not seen if tested under HCI smoking conditions. As for other nitrogen-containing smoke constituents, there are categorical differences between American-blend and Virginia-type cigarettes due to the higher nicotine content in Burley tobacco data from Gregg et al.

Additional studies were performed to characterize the effect of using sugars as tobacco ingredients, which analyzed less comprehensive lists of smoke constituents compared to the above experiments. Pyrolysis experiments had suggested the formation of furfural from sugars. Since Burley is practically devoid of sugars, this study also showed that other tobacco components also give rise to the formation of furfural. This study also confirmed the general increase in carbonyl constituents by the presence of sugars in the tobacco blend. With radioactive labeling, further products of glucose and sucrose used as cigarette ingredients were identified in mainstream smoke Gager et al.

These include furan, alkylated derivatives of furan, and acetonitrile. None of these constituents was found at recoveries of more than 0. Some constituents found in this tracer study were also included in the above pooled analysis of mainstream smoke constituents, but did not show a statistically significant increase with increasing sugar application levels in the pooled analysis. These constituents include acetone and crotonaldehyde. Acetone had the highest radiochemical yield of 0. Two of four individual studies of the pooled analysis indeed showed a statistically significant increase in nicotine-based acetone yields.

No effect was seen in the pooled analysis for crotonaldehyde. The mainstream smoke of research cigarettes manufactured without added sugar or with several levels of sugars applied as tobacco ingredients was quantitatively analyzed for constituents that have been considered to be of major toxicological relevance.

The results of several studies of similar designs were pooled to increase the power of the statistical analyses in this review. In general, under ISO smoking conditions, a trend towards increasing nicotine-based yields of carbonyl constituents was observed, although with distinct differences among the particular carbonyl constituents. The most important increases were observed for formaldehyde and acrolein.

A notable exception was acetaldehyde, which did not change with increasing sugar application levels. Furthermore, a decrease in the nicotine-based yields of several nitrogen-containing constituents was observed. The trends observed in this pooled analysis are in line with the findings of pyrolysis experiments. Similar trends were also observed if sugars were major parts of ingredient mixtures applied to research cigarettes.

Sugar application-dependent effects were found to be less pronounced if smoke was generated under more intense smoking conditions. It should be considered that although the pooled analysis covers a list of 36 smoke constituents, which are considered representative of the major chemical classes of smoke constituents, it is only a small percentage of the number of approximately constituents currently known Rodgman and Perfetti, It is of note that all results in this section were based on the respective nicotine yield of the research cigarettes, which had to decrease with increasing sugar application levels.

Thus, the nicotine-based yield data obtained in the individual or pooled analyses need to be interpreted in view of a trend to decreasing nicotine yields, which automatically could be considered an exaggeration of positive trends or an attenuation of negative trends with increasing sugar application levels compared to a more conventional way of reporting smoke constituent data on the basis of the number of cigarettes smoked or TPM or tar levels.

The pooled analysis revealed complex changes in smoke composition with, e. Moreover, known hazards and risks of these compounds do in general not refer to them as constituents of a complex mixture but rather as neat compounds. Of the constituents identified as increasing with increasing sugar application levels, formaldehyde and benzene are classified as known human carcinogens, with predominant risks for nasopharyngeal cancer and hematopoietic malignancies, respectively International Agency for Research on Cancer, ; International Agency for Research on Cancer, N-nitrosonornicotine and 4-aminobiphenyl, the yields of which were found to decrease with increasing sugar application levels, are also classified as human carcinogens International Agency for Research on Cancer, ; Baan et al.

N-Nitrosonornicotine can produce respiratory tract tumors in laboratory animals and has been classified as human carcinogen based on mechanistic considerations, whereas 4-aminobiphenyl increases the risk for bladder cancer. A role of these smoke constituents in developing smoking-related cancer has been suggested but is unclear in terms of quantitative contributions and modes of action.

For example, apart from the causal role for nasopharyngeal cancer, the International Agency for Research on Cancer argued that the overall balance of epidemiological evidence would not support a causal role of exposure to formaldehyde vapor for developing cancer of the oral cavity, oro-and hypopharynx, larynx, and lung International Agency for Research on Cancer, Smoking has been associated with pharynx cancer US Department of Health and Human Services, , and thus, formaldehyde exposure from smoking may well contribute to this disease.

Moreover, smokers are not exposed to just formaldehyde vapor but the whole complex matrix of smoke constituents, with a part of the smoke-borne formaldehyde residing in the particulate matter of smoke Baker and Chang, This may change its potency and target organ specificity relative to pure formaldehyde inhalation. Using cancer extrapolation models from rats to humans Conolly et al. This estimate is much below the epidemiologically observed risk for respiratory tract cancer by smoking. However, this estimate is based on a model with large uncertainties Crump et al.

The proportion of smoking-induced total leukemia and acute myeloid leukemia attributable to the benzene taken up from cigarette smoke was assessed by combining epidemiologic data on the health effects of smoking with risk assessment techniques for low-dose extrapolation Korte et al. Acrolein is the strongest irritant Dorman et al. It has been suggested to play a role in smoking-related pathogeneses Hecht, ; Rahman and Adcock, but, as for all other constituents, no quantitative attribution to the etiology of smoking-related diseases has been established. Thus, it is not obvious how to interpret these relative changes with increasing sugar application level in terms of the overall risks for cancer and non-malignant diseases for smokers.

Acrolein, benzene, formaldehyde, and N-nitrosonornicotine are also in the list of nine that was recommended for regulatory control of cigarette emissions Burns et al. The other smoke constituents found to increase with increasing sugar application level in the pooled analysis were 2-butanone, isoprene, toluene, and benzo[ k ]fluoranthene, while N-nitrosodimethylamine decreased. The latter is currently classified as probably carcinogenic to humans International Agency for Research on Cancer, , while isoprene, benzo[ k ] fluoranthene and styrene, which was increased in the combined analysis of the HCI data are classified as possibly carcinogenic to humans International Agency for Research on Cancer, ; International Agency for Research on Cancer, ; International Agency for Research on Cancer, Toluene is not classifiable as to its carcinogenicity to humans, and 2-butanone is not listed at all.

For non-cancer effects, toluene has been regulated based on neurological effects seen in humans US Environmental Protection Agency, , while 2-butanone has been regulated based on developmental toxicity US Environmental Protection Agency, It is unclear whether any of the above toxicological properties of these constituents are indeed relevant for human smoking-related diseases. Within the scope of the current assessment, the findings obtained in the chemical-analytical investigations of mainstream smoke were in the following section put into the broader perspective of biological toxicological tests utilizing the whole smoke or major fractions thereof, instead of concentrating on individual smoke constituents.

In further sections, information was considered on smoke composition, exposures, and disease risks in major markets with predominant use of either American-blend or Virginia-type commercial cigarettes, which differ in their use of sugars as tobacco ingredients. The mainstream smoke of research cigarettes without or with various levels of sugars was investigated in in vitro cytotoxicity and genotoxicity assays, in vivo inhalation toxicity studies with primary emphasis on irritative changes in the respiratory tract, and in dermal tumorigenicity studies. The results of studies with similar design were pooled in analogy to the evaluation of the chemical composition.

Cytotoxicity has been identified as a major toxicological activity of mainstream smoke and has been used for benchmarking comparisons Roemer et al.

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In order to improve the power of the current analysis, studies with applications of sugars as the sole ingredients Roemer et al. There was a statistically significant decrease in cytotoxicity activity for the particulate phase with increasing sugar application levels Figure 4A , TPM-based comparison.

This effect would not have been detected by evaluating these studies individually, except for study 3 using honey as an ingredient Coggins et al. The results of the current analysis are consistent with those studies, in which sugars were used as a major part of ingredient combinations at individual application levels up to No increase in in vitro cytotoxicity ED 50 per puff or ciliatoxicity effect after 4th puff was seen in an early study on non-filter American-blend or single-blend Burley research cigarettes with and without 5.

The legend in graph A also applies to graph B; for study references, see Table 3. The mutagenicity of the particulate fraction of mainstream smoke has mostly been tested in the plate incorporation version of the Salmonella typhimurium reverse mutation assay, e. This assay is required for regulatory reporting in Canada Health Canada, For this type of investigations, the respective OECD guideline Organization for Economic Co-operation and Development, a was adapted to the comparative testing of various types of smoke-derived test materials.

The most sensitive tester strains are TA98 and TA in the presence of a metabolic activation system S9. In pooling data sets on sucrose, invert sugar, honey, and HFCS from various studies and laboratories Roemer et al. No sugar application-dependent effect on mutagenicity was reported in any of the individual studies, including the results obtained with other tester strains and in the absence of metabolic activation e. TA with and TA without metabolic activation: Figure 5C and D. Various other studies used sugars in ingredient combinations at individual sugar levels up to Also, no difference was detected for these variations in sugar application in a sister chromatid exchange assay in Chinese hamster ovary cells.

In an earlier study, in which cigarettes were soaked in solutions containing various types of sugars, also no increase in bacterial mutagenicity was observed for TA and rather a decrease for TA98 Sato et al. Bacterial mutagenicity TPM-based of the mainstream smoke particulate phase of research cigarettes with varying sugar application levels relative to the respective control. The legend in graph A also applies to graphs B to D; for study references, see Table 3. Subchronic inhalation toxicity studies in rats have become the most commonly used in vivo study type for the investigation of potential effects of changes in cigarette design on mainstream smoke toxicity Terpstra et al.

Several studies were reported in which the effects of using sugars as tobacco ingredients on the toxicity of mainstream smoke were investigated. These studies were in general conducted in accordance with the respective guidance from OECD Organization for Economic Co-operation and Development, with adaptation to the comparative investigation of smoke generated from different research cigarettes. During the day inhalation period, clinical observations were conducted, body weight and food consumption were measured, and pulmonary function tests were performed.

At scheduled necropsies, blood was collected for clinical pathology measurements, major organs were weighed, and tissues were collected for histopathological evaluation. The major emphasis in these studies was on potential effects in the respiratory tract. Some studies included a day post-inhalation period to investigate the sustained development or recovery of effects.

The effects of sucrose and invert sugar, each at various application levels, were investigated in a large study, which shared the same control without sugar application Table 4 Coggins et al. No such increase was found for acetaldehyde and acrolein. Analysis of exposure markers, such as blood cotinine or carboxyhemoglobin levels, as well as respiratory parameters, documented similar inhalation for the groups exposed to the smoke generated from the research cigarettes with the various levels of sugar applications. The usual smoke inhalation-related biological effects, such as a decreased gain in body weight and irritative changes in the respiratory tract epithelia, were observed.

Increased incidence and severity score for respiratory epithelial hyperplasia at nasal level 2 was observed in male but not in female rats at the high sucrose application level. Significant differences were not observed for the low and medium sugar application levels up to 7. After a day post-inhalation period, this effect had recovered.

A few other findings were higher in rats previously exposed to smoke from cigarettes containing the highest sugar level than in those rats exposed to smoke from control cigarettes in one but not the other gender. Histopathological findings mean severity scores with significant differences between rats exposed to the smoke of research cigarettes with and without sugars applied as tobacco ingredients at the end of at least one subchronic rat inhalation study on mainstream smoke from research cigarettes with various application levels of sugars: Additional groups not shown here: Air-exposed sham group as negative control, groups exposed to mainstream smoke of 1R4F standard reference cigarettes as quality control.

The same laboratory conducted another large subchronic inhalation study with the same study design, in which research cigarettes with various application levels of HFCS alone Coggins et al. The concentrations of formaldehyde but not those of acet-aldehyde or acrolein in the test atmospheres increased with increasing sugar application levels. The only significant effects in this study were significantly higher goblet cell hyperplasia scores in the tracheas of female rats in groups exposed to the smoke of the test cigarettes with dual combinations of sugars at a total 6.

This effect was not seen with 6. Few incidental effects were seen after the end of the post-inhalation period. Conditions as in Table 4 , except of 2R4F as quality control. A third subchronic inhalation study was conducted by the same laboratory and with the same study design using honey as the ingredient to be tested Coggins et al.

Again, formaldehyde concentrations in the test atmospheres were found to increase with increasing honey application levels in the test cigarettes, while there was no effect on the other aldehydes determined. The histopathological endpoints that showed significant sugar application-dependent differences in the above studies that tested sucrose, invert sugar, and HFCS were not different in this study Table 6. However, a significant increase was seen for bronchial goblet cell hyperplasia in both males and females at the highest honey application level compared to control.

No other significant differences were observed in the groups exposed to the smoke of the research cigarettes with honey, except of an increase in severity of olfactory epithelium atrophy at nose levels 2 and 3 of the male rats in the group exposed to the smoke of the research cigarettes with 6. Such significant difference was not seen in female rats. There were no differences apparent after a 6-week post-inhalation period. No effect was seen at the 4. Thus, in the current inhalation study, significant changes in groups exposed to smoke from research cigarettes with applied sugars vs.

Histopathological findings mean severity scores with significant differences between rats exposed to the smoke of research cigarettes with and without honey applied as tobacco ingredient at the end of at least one subchronic rat inhalation study on mainstream smoke from research cigarettes with various application levels of sugars Coggins et al.

Although there were some significant differences in the groups exposed to the smoke generated from the research cigarettes with the highest sugar application levels, these were not consistently found when comparing between genders or between studies, suggesting that the few findings recorded were possibly due to chance rather than causally linked to the use of sugars as tobacco ingredients in these research cigarettes.

If these differences would be triggered by the high sugar application level, one would expect to see very similar differences across those studies and across the sugars tested, based on the similarity of the changes determined in the comprehensive chemical-analytical studies on the mainstream smoke of these research cigarettes see above.

In any case, these differences were only observed at application levels higher than those usually applied to commercial cigarettes, although findings at exaggerated application levels may be indicative of effects at commercial application levels. More light may be shed on this question by examining additional subchronic inhalation studies, in which research cigarettes with combinations of tobacco ingredients, including a major contribution of sugars, were evaluated.

A study with similar design to the ones discussed above had sucrose and invert sugar incorporated into a an ingredient mixture with total sugar application levels of 3. Very similar smoke inhalation-dependent effects were seen, e. None of the differences discussed above for the sugar application studies was seen as a function of the ingredient mixture application. Among the multitude of endpoints investigated, there was only one significant increase observed for respiratory epithelium hyperplasia at nose level 1 in female but not male rats in the high sugar combination group.

In another large study, brown and white sugar as well as invert sugar were used on research cigarettes as major part of different tobacco ingredient combinations at levels of 6. The authors concluded that there were no discernible differences in the type or severity of treatment-related changes in the presence or absence of the ingredient combinations that included sucrose as brown or white sugar or invert sugar, since there were no statistically significant differences between rats exposed to the smoke from the control and test cigarettes in any of the 32 histopathological endpoints.

These authors concluded that the presence of flavoring and casing ingredients did not significantly change the type or extent of toxicological effects observed in rat inhalation studies. As for some in vitro endpoints, no differences in response in subchronic inhalation studies in rats were observed if one type of sugar was replaced by another at the same application level no controls without sugar application; Stavanja et al.

As part of the above subchronic inhalation studies with single sugar ingredients studies 1, 2, and 4 using sucrose, invert sugar, or high fructose corn syrup , the formation of micronuclei in rat bone marrow polychromatic eryth-rocytes and peripheral reticulocytes was investigated as an endpoint for in vivo clastogenicity in basic accordance with Organization for Economic Co-operation and Development, b.

Peripheral reticulocytes were analyzed using a flow cytometric method capable of differentiating very young cells to overcome the splenic trapping of micronucleated cells which could have confounded this rat model van Miert et al. Inhalation exposure to mainstream smoke for up to 13 weeks did not increase the incidence rates of micronucleated reticulocytes in circulating blood, nor micronucleated erythrocytes in bone marrow compared with sham-exposed controls data not shown.

Although there were occasional significant differences between the groups exposed to smoke from cigarettes containing sucrose and invert sugar and those exposed to smoke from control cigarettes without added sugars, the overall conclusion was that the sugars had no impact on the formation of micronucleated red blood cells.

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Positive control samples responded in accordance to historical data from the same laboratory at all time points, indicating sensitivity of the rats to materials producing micro-nucleated cells. For a long time, mouse dermal carcinogenicity studies have been the only cancer bioassay available for cigarette smoke reviewed by Coggins, ; Walaszek et al. In this assay, mainstream smoke condensate is chronically painted on the dorsal skin of mice, and skin tumors are the major biological response, which can be non-invasively examined on a daily basis. There are two principle experimental variants for this assay: Condensate is either applied to the skin during the whole experimental period as a test for complete carcinogenesis, or condensate is applied during the major experimental period of the study as a test for its promoting activity after initial treatment with a low dose of a known mouse dermal carcinogen, low enough not to lead to tumors on its own.

There is one set of experiments, in which cigarettes with and without invert sugar were compared in a complete carcinogenesis model US Department of Health Education and Welfare, The standard experimental blend in this study was made according to then non-filter American-blend cigarettes and included 5. It was compared to the same blend but without sugars. Groups of mice were treated with two doses of each condensate for 18 months.

Statistical analysis revealed that the research cigarettes with and without invert sugar ranked very similarly for both dose groups, i. If the tobacco humectant was omitted in one test cigarette, no difference in tumorigenic potential was seen in comparison to the reference cigarette containing the humectant. However, if both humectant and invert sugar were omitted, the condensate generated from the test cigarette had lower tumorigenic activity than that of the control no explanation offered by the authors.

In a parallel experiment, single-blend Burley cigarettes without and with sugar addition were compared twice at the same dose and no difference in tumorigenic response of the condensates was observed Table 5. Notably, in the same study the condensates of Burley and American-blend cigarettes could well be differentiated.

Taken together, these experiments suggest that sugar by itself had no impact on the tumorigenicity of smoke condensate in the mouse dermal carcinogenicity assay. Dermal tumorigenicity of mainstream smoke condensate generated from research cigarettes with and without invert sugar as tobacco ingredient. Life-table-corrected data US Department of Health Education and Welfare, no sugar-dependent differences for formaldehyde, acetaldehyde, acrolein, and tar yields.

No other carcinogenicity study is available comparing cigarettes with appreciably different levels of sugars. In a study to evaluate the tumorigenic activity of research cigarettes without and with a combination of flavors, the test cigarettes had additional glucose and honey at 0. Complimentary to the chemical-analytical investigations, in vitro cytotoxicity, genotoxicity, subchronic inhalation, and carcinogenicity studies have been available for the non-clinical assessment of the toxicological effects of using sugars as ingredients.

This is particularly important in view of the statistically significant increases in nicotine-based yields of acrolein and formaldehyde observed in smoke from cigarettes with increasing sugar application level. Formaldehyde and in particular acrolein play relatively prominent roles in the in vitro cytotoxicity assay Tewes et al. At higher acrolein concentrations, mucus hypersecretion in the airways of rats was stimulated Borchers et al. At no-toxic effect levels, neither additive nor potentiating effects occurred from the combined exposure to these aldehydes Cassee et al.

In principle, the lack of additive or potentiating effects in defined mixtures of aldehydes does not exclude an additive or potentiating effect by the increased aldehyde levels on the background of smoke-related findings seen in these inhalation studies, but such effect was not observed. Thus, the totality of the reviewed studies suggests that the increased aldehyde yields determined in the chemical analyses did not increase the activity of the smoke in toxicological assays that are in principle sensitive to their activity.

Moreover, the overall changes by the use of sugars as ingredients determined in the chemical analyses may either have balanced each other out or were not large enough to significantly affect the toxicological activity that is inherent to cigarette smoke in the assays employed. The above non-clinical studies should ideally be complimented by clinical and epidemiological data on exposure and effects differentiating between smokers smoking cigarette types with and without sugars used as tobacco ingredients.

However, such data for a direct comparison of commercial cigarette types that differ by only this one parameter are not available, with the exception of menthol versus non-menthol cigarettes Werley et al. As a substitute, we compared data from markets of primarily American-blend and Virginia-type cigarette consumption, respectively. These cigarette types differ in their blend composition, but also in their natural sugar content and the level of sugar applied as ingredient. The chemical composition of mainstream smoke generated from American-blend and Virginia-type cigarettes is qualitatively similar, with some quantitative differences, most of which can be explained by the differences in tobacco blend composition.

For instance, the higher yields of nitrogen-containing smoke constituents observed for single-blend Burley compared with single-blend Virginia research cigarettes Adam et al. High molecular weight polycyclic aromatic hydrocarbons, such as benzo[ a ]pyrene and benzo[ k ]fluoranthene, are formed at lower yields in the mainstream smoke of single-blend Burley than in that of Virginia research cigarettes Ding et al. This difference has been related to the higher nitrate content in Burley-containing cigarettes, which may interfere with the pyrolytic formation of polycyclic aromatic hydrocarbons.

Formaldehyde yields are generally lower in the smoke of American-blend than in that of Virginia-type cigarettes, which is considered to be related to the lower overall sugar content and higher levels of nitrogen-containing compounds Leffingwell, in American-blend compared to Virginia-type cigarettes. The pooled chemical analyses of the mainstream smoke of research cigarettes as described above suggested that there are statistically significant increases in the slopes of the linear regressions in the nicotine-based yields of seven smoke constituents with increasing sugar application levels, most importantly for formaldehyde, benzene, and acrolein.

Consequently, marketed American-blend cigarettes, which do not have a higher total sugar content than marketed Virginia-type cigarette, do not show an increased yield of these smoke constituents in direct comparisons Table 8. For acrolein, 2-butanone, benzene, and toluene, no relevant differences in nicotine-based yields were found when comparing American-blend and Virginia-type market cigarettes. This agrees with the findings of numerically lower nicotine-based yields for benzo[ a ] pyrene, which is mostly determined as the only representative of this class of constituents, for American-blend versus Virginia-type market cigarettes Table 8.

Thus, the use of sugars as ingredients may not cause any concerns regarding this class of smoke constituents. As mentioned above, the largest difference in the composition of the smoke generated from American-blend or Virginia-type cigarettes stems from nitrogen-containing compounds Table 6. Of these, nicotine-based yields of N-nitrosodimethylamine, N-nitrosonornicotine, and 4-aminobiphenyl were found to decrease in a statistically significant manner with increasing sugar application levels in the pooled analysis.

Taken together, those constituents found to significantly increase in research cigarettes with increasing sugar application levels were similar or even lower in American-blend than in Virginia-type market cigarettes, whereas the use of sugars as tobacco ingredients in American-blend cigarettes attenuates the yields of some of those constituents which are high in American-blend compared to Virginia-type market cigarettes. Selected mainstream smoke constituent yields per mg nicotine for marketed American-blend and Virginia-type cigarettes Counts et al. In summary, in American-blend compared to Virginia-type cigarettes, parts of the Virginia tobacco are replaced by Burley tobacco, which is practically free of sugars.

The resulting decrease in the natural sugar content in the blend is partly replenished by applying sugars as ingredients to levels at or below that found in Virginia-type cigarettes. Thus, the sugar-dependent findings in the pooled analysis of smoke constituent yields from research cigarettes do not carry over to increased yields of these constituents in the blended cigarettes compared to Virginia-type cigarettes.

For instance, the observed increases in formaldehyde, acrolein, or benzene by sugar application to research cigarettes do not result in higher average yields of these constituents in American-blend compared to Virginia-type cigarettes. On the contrary, formaldehyde yields tend to be higher on average in Virginia-type cigarettes. The sugar-dependent decreased yields of some nitrogen-containing smoke constituents seen in the pooled analysis of the research cigarettes alleviate the naturally higher yields of these constituents in the smoke from Burley-containing cigarettes.

The comparative activity of American-blend and Virginia-type cigarettes was assessed in in vitro cytotoxicity and genotoxicity assays, mostly by using the mainstream smoke of reference cigarettes representative of the two types of market cigarettes. Smoke from Virginia-type cigarettes was consistently more cytotoxic than that of American-blend cigarettes Bombick et al.

These results are consistent with the tendency to higher cytotoxicity of Virginia compared to Burley single-blend research cigarettes Pickett et al. In the Salmonella reverse mutation assay, mainstream smoke condensate from American-blend cigarettes was consistently more mutagenic than the condensate of Virginia-type cigarettes Mizusaki et al.

This result is consistent with the higher mutagenicity of smoke from Burley tobacco compared with that from Virginia tobacco Mizusaki et al. In mammalian cell-based genotoxicity assays, in contrast to the bacterial assay and depending on the specific assay type used and on the laboratory conducting the assay , particulate matter from single-blend Burley mostly tended to be less active than that from Virginia cigarettes Schramke et al. In subchronic inhalation studies, the smoke from Virginia-type cigarettes seemed to have higher potency than that of single-blend Burley or American-blend cigarettes regarding histopathological changes in the larynx compiled by Smith, Histopathological findings in the trachea and lungs were of similar degree.

Dermal carcinogenicity studies in mice were not able to clearly differentiate between the condensates generated from American-blend and single-blend Virginia and Burley research cigarettes. If anything, there was a trend towards slightly higher tumorigenic potency for Virginia than Burley condensate, with that of the American-blend cigarettes being somewhat intermediate Wynder and Hoffmann, ; Dontenwill et al. The comparison of the market cigarette types indicates that the differences in toxicity observed between the smoke of Virginia-type and American-blend cigarettes appear to reflect the toxicity of the tobacco blend components rather than the application of sugar.

Current scientific knowledge does not allow a conclusion about which of these assay types or particular endpoints are more predictive of the induction of smoking-related diseases in humans. In summary, the results of the toxicological assays on research and market cigarettes confirm that cigarette smoke is toxic; however, they also suggest that the use of sugars applied to the tobacco of American-blend cigarettes at current use levels is unlikely to increase the inherent toxicity of tobacco smoke.

In order to further evaluate the changes in mainstream smoke chemistry that were determined in the pooled analysis described above as a consequence of using sugars as cigarette tobacco ingredients, a simulation of the differential smoking-related exposure to those constituents was performed, for which statistically significant quantitative changes were identified.

This approach offers the most discriminatory analysis of potential changes in mainstream smoke exposure resulting from the use of a particular ingredient in a research cigarette, but it has some limitations with regard to the extrapolation of the results to market cigarettes and their actual use by consumers. Most information on exposure and uptake of cigarette smoke constituents has been generated for nicotine via the determination of nicotine and some of its major metabolites in human body fluids, such as saliva, plasma, or urine.

Assuming proportional relationships between the yields of nicotine and most other constituents Roemer et al. Such uptake distributions offer a more informed estimate of the impact of potential changes in smoke composition than just point estimates for nicotine uptake.

Using Monte Carlo simulation, the mean and standard deviation of nicotine equivalents determined in a German population-based biomonitoring study with American-blend cigarettes Scherer et al. This approach enables calculation of uptake distributions per cigarette which provide insight beyond the simple results of standard machine-smoking conditions and incorporates the variability of human smoking behavior as best as possible. This variability is reflected in the broad distribution of the uptake of nicotine equivalents after Monte Carlo simulation Figure 6 and propagates to the distribution simulated for any of the other constituents.

A log-normal model was used for the simulation, which seems to be justified in view of more recent and more detailed distribution data on nicotine uptake Mendes et al. The same simulation was applied to the average nicotine-based yields of smoke constituents of the market cigarettes. Monte Carlo simulation of the nicotine uptake distribution based on nicotine equivalents from a population-based biomonitoring study with smokers of American-blend cigarettes. Data from Scherer et al. For the validation of this approach, the simulations for acrolein uptake were compared with the acrolein yields of market cigarettes Counts et al.

This is possible since practically all nicotine and acrolein inhaled from smoking are absorbed Baker and Dixon, The median acrolein uptake per cigarette determined by the simulation is similar to the average yield obtained when this selection of cigarettes was smoked under intermediately intense conditions Massachusetts General Laws Annotated, This similarity is reasonable as in a recent review on actual human smoking conditions Bernstein, , median values for interpuff interval, puff duration, and puff volume of 28 s, 1.

Machine-smoking data compared to the fitted log-normal Monte Carlo simulation of acrolein uptake using Crystal Ball; left panel: Health Canada smoking conditions Health Canada, ; right panel: American-blend market cigarettes, violet line: The uptake distributions for benzene Figure 8A , toluene, benzo[ k ]fluoranthene, and NDMA also overlapped to a very large degree indicating no relevant difference by sugar application and market type cigarette. Uptake distributions per cigarette are also shown for formaldehyde Figure 8B and 4-aminobiphenyl Figure 8C representing smoke constituents with the largest percentage increases or decreases in nicotine-based yields with increasing sugar application levels.

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The hypothetical uptake of 4-aminobiphenyl was higher for American-blend than for Virginia-type cigarettes, while it got smaller with sugar application. Thus, the uptake simulations reflect the changes in the point values determined in the pooled analysis of the research cigarettes or the differences in the average yield data of the market cigarettes, but these changes and differences are put into the perspective of the broad inter-individual variability in the uptake of these constituents by smokers.

For color legend, see explanations for the right panel in Figure 7. In a recent benchmark study for biomarkers of exposure to smoke constituents, groups of smokers from Germany and the UK as prototypic markets of American-blend and Virginia-type cigarettes were compared Lindner et al. Smoking-attributable excretion levels of 3'-hydroxypropyl-mercapturic acid, a urinary acrolein-related biomarker of exposure, were 1.

For S-phenylmercapturic acid, a marker for benzene exposure, urinary marker levels were 3. Thus, the biomarker data confirm the similarity of exposures to these constituents on the basis of means and standard deviations as a measure of variance by the two types of cigarettes as suggested by the current modeling approach based on analytical-chemical data. The authors concluded that the contribution of the country and thus the type of cigarettes smoked to the total variation was marginal for all biomarkers of exposure investigated Lindner et al. The above approach of bridging from the uptake of nicotine to that of other smoke constituents is only reasonable as a determinant of potential changes of exposure by the use of sugars as ingredients, if there is no change in smoking behavior to be expected.

There are no studies available that have assessed the potential direct effect of using sugars as ingredients on smoking behavior. Thus, it is not expected that there would be any difference in overall smoke exposure from using sugars as ingredients. This interpretation is further corroborated by the lack of differences for nicotine uptake per cigarette from smokers from various regions of the world including those of predominantly American-blend and Virginia-type markets, which among other parameters differ by the use of sugars as ingredients Figure 9A.

The intake of nicotine per cigarette was also considered to be similar in a study that included smokers from Brazil, Mexico, China, and Poland Blackford et al. However, when the cigarettes across the countries were separated into Virginia- and American-blend types, overall MLEs for smokers of Virginia-type cigarettes were significantly greater than those of American-blend smokers, reflecting differences and preferences in ISO yields. Thus, no clear trend that could be related to the use of sugars as ingredients could be observed either. Such an ecological approach of comparing markets has also been chosen by the International Tobacco Control Policy Evaluation Survey Hammond et al.

Estimated nicotine uptake from plasma, urine based on nicotine equivalents for plasma and urine , or cigarette filter analyses mouth level exposure. Cigarettes of American-blend Byrd et al. Further variables of smoking behavior in a population are smoking prevalence and intensity. Smoking prevalence data have been published by many national and international sources. Data published by the World Health Organization demonstrate wide international differences in smoking prevalence MacKay and Eriksen, ; World Health Organization, , but do not indicate trends by the predominant type of cigarette smoked in a particular country Figure In an extensive study comparing exposure and chronic disease risk between countries with predominant American-blend United States, Germany, Austria, and Denmark and countries with predominant Virginia-type smokers United Kingdom, Australia, and Canada , stratified by age group, gender, and time periods from to , no overall statistically significant difference in smoking prevalence could be detected Lee et al.

The ex-smoking prevalence was generally increasing over the time periods investigated in both sexes and all age groups and was lower in American-blend than Virginia-type markets, although only rarely with statistical significance. They concluded that predictors of making quit attempts and cessation were similar for each of the four countries.

Although there were some differences among the countries in predictors of success, such as heaviness of smoking index, favorable attitudes about smoking, and self-efficacy, these differences could not be associated with American-blend or Virginia-type preferences in these countries.

Smoking prevalences in American-blend and Virginia-type cigarette markets. The most frequent measure of smoking intensity is the number of cigarettes smoked per day. For this variable over all time periods and age groups, no difference was observed between American-blend and Virginia-type markets, while smoking intensity was higher in males than in females approximately 20 vs.

This gender difference in smoking intensity and the lack of difference between American-blend and Virginia-type markets Figure 11 can also be derived from data from the International Tobacco Control Policy Evaluation Survey Hammond et al. Those scores were inversely related to smoking prevalence rates in these countries, which again puts the Virginia-type market into the range observed for American-blend markets.

Likewise, no distinction could be made for a number of smoking dependence-related parameters, including smoking intensity, heaviness of smoking index, and number and duration of quit attempts, between smokers from American-blend and Virginia-type markets Shahab et al. National Drug Strategy Household Survey.

Summarizing the data detailed above, there are no indications that the use of sugars as ingredients, which is one characteristic of American-blend cigarettes, has any influence on smoking behavior and behavior-related exposure, either in terms of cigarette smoking prevalence, the frequency of quit attempts, smoking intensity as cigarettes per day, and nicotine uptake. In addition, these data do not in any case support the suggestion that the use of sugars as ingredients or any other ingredients in American-blend cigarettes would lead to an increased dependence potency by whatever mechanism hypothesized.

Predominantly American-blend and Virginia-type markets were compared for the risks of mortality from smoking-related lung cancer and COPD Lee et al. Unadjusted mortality rates were generally lower early on in markets with predominant Virginia-type cigarettes, with the difference diminishing or reversing by the s.

Differences by cigarette type were rarely significant for age and time period groupings, due to variations, particularly for COPD, between countries within cigarette type. Conclusions based on estimated smoking-related excess mortality were similar to those based on unadjusted mortality rates: There was little indication of any difference between American-blend and Virginia-type cigarettes on risk of lung cancer or COPD. The approach of this study had of course less discriminative power than any analytical-chemical study, which is partly due to unspecified differences between countries with the same type of predominant cigarette type.

This is similar to the discriminatory power of many subchronic laboratory animal inhalation studies. With the most discriminatory non-clinical endpoints for the evaluation of mainstream smoke, such as chemical analysis or in vitro assays, differences in both directions can be detected between American-blend and Virginia-type market cigarettes. With the current state of knowledge, it is not clear which of these endpoints would be more relevant than others in predicting human health issues.

No relevant difference between American-blend and Virginia-type cigarettes was detected for smoke exposure and effects, including measures for smoking dependence and smoking-related chronic diseases. Thus, with the current means of investigation of these endpoints, there is no indication of any relevant effect of using sugars as ingredient in commercial cigarettes. The current assessment is considered a comprehensive evaluation of the evidence available on the potential effects of using sugars as ingredients.

However, no such assessment can be without limitations, because cigarette smoke is a complex mixture of constituents and smoking-related diseases have complex chronic pathogeneses. Nevertheless, the scope of the current assessment went beyond standard ingredient assessments by industry or regulatory authorities, e. There are areas for which appropriate studies are missing and for practical reasons will continue to be missing. One example is the lack of a direct comparison of smokers smoking American-blend cigarettes with and without sugars applied as ingredients for the evaluation of a potential impact on smoking prevalence, smoke exposure, and smoking-related biological effects.

An American-blend cigarette is defined by using sugars as ingredients, and the combustion products of these sugars in the tobacco matrix contribute to the overall flavor of such cigarettes thus enhancing the natural taste characteristics of the tobacco. A hypothetical clinical study comparing smoke exposure from cigarettes with and without sugars as ingredients would intrinsically be confounded by the uncommon taste of the test cigarettes without sugar.

In order to assess this question in a more indirect manner, the best opportunity was considered to be a comparison of markets with smokers predominantly smoking American-blend cigarettes with added sugars and those predominantly smoking Virginia-type cigarettes without added sugars. However, these two types of cigarettes also differ in their natural content of sugars, resulting in similar or even lower overall sugar content in American-blend cigarettes compared to Virginia-type cigarettes.

There has been a broad agreement for the selection of smoke constituents or in vitro assays considered to be appropriate for such assessments between industrial and independent laboratories as well as the few emerging regulations e. Health Canada, ; Gregg et al. Nevertheless, only a selection of constituents or toxicological activities is being assessed, assuming that the results of the selected endpoints would be representative of other constituents and biological endpoints.

In order to increase the relevance of the non-clinical toxicological testing, subchronic inhalation studies have been included for the assessment of major cigarette ingredients, such as for sugars. A comprehensive array of potential target organs and tissues has often been included in the evaluation of these inhalation studies in line with Organization for Economic Co-operation and Development, including, e. The non-clinical assay types reviewed here have been taken over from those used in other areas of regulatory toxicology.

While their suitability for assessing the toxicity of smoke has not finally been established, this is not specifically the objective of cigarette ingredient testing anyhow. The objective is rather to determine that no significant toxicity is added to that intrinsic to tobacco smoke, either of the same type or new. Thus, classic regulatory toxicity tests may fit well to the testing of cigarette ingredients, if appropriately adapted to deal with the intrinsic toxicity of smoke and the resulting need for comparative testing.

The bacterial mutagenicity assay may not be the optimal tool to evaluate the genotoxic property of smoke per se , but it may serve appropriately for the detecting of potential changes in genotoxic potency of smoke samples. For the testing of ingredients, the assay has been adapted to describe a linear dose-response relationship with smoke TPM, and the slope obtained with the test samples generated from experimental cigarettes with various ingredient application levels is compared in a quantitative manner Roemer et al. The in vitro cytotoxicity assay has proven to be particularly useful for the assessment of cigarette smoke, as it relates to the irritative potency of smoke seen in in vivo studies.

In in vitro genotoxicity studies with smoke, cytotoxicity has always been a limiting factor for dosing and interpretation thus demonstrating the relevance of this particular activity in assessing the complex toxicity of smoke. Smokers in the Maghreb used a distinctive dry-pipe design for consuming mixtures of tobacco and cannabis. In Egypt, people mostly consumed cannabis resin imported from Turkey and Syria. For instance, 19th-century Algerian hunters smoked before going out; 48 current Moroccan fishers use cannabis to improve night vision, a pharmacologically verified effect.

Nowadays, psychoactive cannabis is called kif , an Arabic word for a state of deep mental and spiritual awareness. Water-pipe smoking was a common element in 19th-century European Orientalist art. Kieff Yaoos [Sweet Repose]. The ethnonym Tekruri eventually applied to people across the Sudanian region. The name tekruri for cannabis was also recorded in near Zinder, Niger, 51 which was formerly within the Kanem-Bornu Empire. Kanem-Bornu had controlled trans-Saharan trade from the central Sudanian region between and CE, and maintained embassies in Libya and Morocco.

Cannabis probably travelled north via Kanem-Bornu. There is scant documentation of cannabis in Ethiopia. Cannabis grew in Madagascar over 2, years ago. Its only documented use has been as a smoked drug. Antler-based water pipes were used with tobacco in ; bamboo-based dry pipes held cannabis about and persisted into the s. The only obvious introduction route to the sub-Saharan mainland is maritime trade across the Arabian Sea to East Africa, which began in the first millennium CE. However, the similarity of names in multiple languages precludes certain identification of cultural linkages.

The ancient value cannabis had in southern Asia doubtlessly carried it into maritime networks, though not necessarily as a trade good. Hindi-, Farsi-, or Arabic-speaking traders presumably introduced cannabis to the Swahili coast, perhaps by CE. Four sets of terms are noteworthy. Scant documentation exists for these traditions. First, plant names in Bantu languages in the Rwanda—Burundi area are similar to urumogi. Second, suruma is shared in geographically and linguistically distant Bantu languages in Zimbabwe, Mozambique, and northern Tanzania.

Third, in central Southern Africa, speakers of Sotho and related languages call cannabis matokwane. Fourth, many Bantu, Nilo-Saharan, and Ubangian languages have cannabis names beginning with a syllable like ja , from central Tanzania to South Sudan and across the northern Congo Basin into Cameroon. Terminal mb terms are discussed further below. However the plant arrived, East Africans transformed its use. Pre-Columbian smoking pipes have been unearthed only inland, although European travelers observed coconut-based water pipes in Comoros in 67 and antler-based ones in Madagascar in Smokers used many different designs of antler-based water pipes in Southern Africa.

Cannabis is poorly documented in East Africa. The first sub-Saharan documentation of cannabis is a Portuguese account of bangue at the mouth of the Zambezi central Mozambique in the s. The document records oral consumption of cannabis, similar to contemporaneous Portuguese Indian sources. There is no subsequent documentation from East Africa until the s, when people in Mozambique smoked it in antler-based water pipes 69 and used it for fiber and non-psychoactive, external medicines.

Cannabis slowly dispersed south and west from the Swahili coast, mostly after To the west, cognates of bangi suggest dispersal via Swahili-led trade into central Southern Africa and the northern Congo Basin. Swahili expansion in these areas occurred primarily after , though cannabis dispersed under the name bangi through cultural interactions far beyond direct Swahili influence.

As elsewhere, cannabis was not necessarily a commodity, but perhaps simply a useful plant. South of the Zambezi, European shipping seemingly introduced cannabis to coastal areas. First, Portuguese residents had consumed cannabis orally in India since the s. Sailors on Portuguese ships likely carried the plant. Second, Dutch ships in the 17th century transported cannabis from Natal to Cape Town for trading with Khoesan peoples. Southern African cannabis is relatively well documented, especially after The plant may have arrived in the Bantu expansion like other crops, yet it became widely known under the Khoesan name dagga , first documented in Important secondary sources are confused regarding the uses and histories of cannabis and Leonotis.

Cannabis circulated in Southern Africa as a trade item. By the s it was important in a regional exchange economy. Playing saliva-bubble game while smoking antler-based water pipe, South Africa, c. The man at left is forming a bubble on the ground through a long reed. Khoesan peoples consumed a variety of psychoactive plants before and alongside cannabis, in spiritual contexts and medicinal applications.

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Beginning in the s, substance use in Khoesan communities was increasingly destructive, causing public health problems that accelerated social disintegration traceable to dispossession by European settlers. While Khoesan—Bantu trade continued, European settlers increasingly supplied alcohol, cannabis, and tobacco, starting soon after when Dutch colonists paid Khoesan laborers with these substances.

Farmers across Africa transformed cannabis through agricultural selection. Botanical evidence of these transformations is adequate only in Southern Africa, where people valued it as an appetite suppressant. Past farmers produced this distinctive strain by selecting plants for appetite-suppressing physiological effects. Finally, cannabis reached western Central Africa in the era of the Atlantic slave trade.

Western African cannabis cultures seemingly trace to the middle Zambezi region, where many languages share plant names like Yao chamba , a ja term with a terminal mb sound. Cognate terms occur westward to the Atlantic, particularly diamba , liamba , and riamba. Angolan trading networks, which transported many goods in addition to enslaved people, reached continually farther inland beginning in the s. Enslaved people from the Zambezi Valley began entering westward coffles in the s, their numbers increasing after about By , cannabis grew widely in Angola, where people smoked it in calabash-based water pipes.

Slaves valued cannabis as a subsistence medicinal plant, and a stimulant. The plant grew as a weed in agriculturally marginal sites. The only known record of seed saving of any plant species by a slave in Africa is an observation from s Gabon, where a man kept cannabis seeds to plant wherever he might disembark. Helena, Sierra Leone, Liberia, and Jamaica. After abolition, cannabis continued to accompany Central African labor migrants. Porters in western Central Africa widely carried small, calabash-based water pipes among their few personal belongings while traveling in trade caravans.

European travelers sometimes bought cannabis for their porters and occasionally admitted smoking it with them. An Afro-Portuguese merchant offered cannabis to entice trade at least once, about , when a dealer visiting what is now southwestern Democratic Republic of Congo introduced a local leader to riamba smoking. In its context, the movement was an example of the social-cultural transformations that swept 19th-century Central Africa.

The Bena Riamba were younger people who overthrew entrenched rulers and the sociocultural status quo. Cannabis was simultaneously a sacrament, medicine, and, in the form of extremely high doses, an instrument of punishment to the Bena Riamba. The movement dissolved into political and ethnic conflict within colonial Belgian Congo.

Central African cannabis was complexly entangled in political-economic transformations. The plant traveled with slaves and laborers, but rulers and traders who enabled slaving also used it. For the Bena Riamba, cannabis helped promote peace, yet warlords and fighters used it too, before and after battle. Current medical practice considers cannabis useful in pharmacologically managing psychological trauma, physical pain, and appetite. African cannabis markets were earliest documented in 13th-century Egypt, and 17th-century Southern Africa.

In the Maghreb, 19th-century markets were highly formalized. By , governments in precolonial Morocco and Ottoman Tunisia both began selling annual monopolies to their cannabis and tobacco trades. Seal of the French Moroccan kif and tobacco monopoly, c. European-controlled trades arose within colonial contexts and mostly supplied hard laborers. Three major trade regions existed, including the Maghreb. In South Africa, European merchants and settlers farmed and traded in cannabis from the late s into the s. Even as these trades developed, colonial regimes increasingly suppressed cannabis.

Rarely, colonial laws rose upon indigenous prohibitions, as in Madagascar, where Merina royalty forbade cannabis by , decades before the French. Many laws clearly served ulterior motives, particularly labor control and religious proselytizing. Cannabis-control laws were unchanged after independence, to keep independent states in compliance with international agreements. Additionally, in a key drug-control agreement in , African states disclaimed indigenous traditions of cannabis use, unlike South Asian countries that legally protected longstanding practices.

Africans have resisted cannabis-control laws through continued production, trading, and use. Black markets grew throughout the s. People smuggled hashish into Egypt under British rule and trafficked cannabis from India through the Suez Canal to supply European markets. Sierra Leonean sailors trafficked cannabis from Gambia to Nigeria; colonial troops carried it widely too.

Lawmakers in Morocco, Rwanda, and South Africa have recently debated cannabis laws, but no African countries have decriminalized it. Although cannabis has deep roots in Africa, tobacco is the preferred smoke across the continent, and worldwide.

Tobacco quickly gained popularity following its introduction from the New World, regardless whether cannabis or smoking was earlier present. Tobacco grew in western Central Africa by and gained great cultural significance over subsequent centuries: Before , carved wood with beads and mirror piece, Brooklyn Museum. Tobacco followed three main dispersal pathways to and within Africa. Most plant names for tobacco worldwide derive from Spanish tabaco. African cognates that lack a central m sound, as in Mandinka taba Senegambia and Benga tobako Gabon , occur mostly in western Africa.

Along the coast, these words came directly from European languages via commerce; the words dispersed inland with the plant. Most cognates in northern and eastern Africa include a medial m sound, including Swahili tumbako. Finally, several Arabic terms other than tombak occur across the Sudanian region, indicating a trans-Saharan dispersal pathway.

European travelers returning from North America introduced tobacco and pipes to Europe in the s. British, French, and Spanish travelers were among the earliest. Iconic white-clay pipes were manufactured in northern Europe—primarily Britain and the Netherlands—based on the Virginian pipe design.

However, initial West African pipe-making industries were based upon a design originally from the southern Mississippi River Valley. Introduction points and dispersal pathways for tobacco in Africa are debated. Khoi laborer smoking European-style dry pipe, South Africa, before Before , pen and sepia ink on paper, National Library of South Africa. In many locations, tobacco was initially a luxury good, and European-style pipes status symbols.

Although farmers widely grew tobacco soon after introduction, imports remained valuable. Africans developed distinctive practices of tobacco use. Farmers grew both Nicotiana rustica and tabacum. African crops widely arose from early Portuguese tobacco trading, which was probably rustica. Native Americans developed several curing techniques that affect flavor; Europeans adopted and innovated many techniques within commercial industries. In Africa, few techniques other than air drying were described before the late s, by which time people were sometimes unwilling to share processing secrets with outsiders.

For instance, in southern Angola, in the s Ovimbundu farmers produced three types of smoking tobacco, and another for snuffing. Some European travelers disdained African tobacco products, though many appreciated them. Where cannabis and tobacco were both present, the two plants had different social meanings. Imported pipe designs, even when made locally, were associated with tobacco; water pipes and indigenous dry pipes mostly went with cannabis.

In many societies, gender- and age-based restrictions differently limited cannabis and tobacco use.

Health effects of tobacco

In Mozambique in , for instance, men and women smoked tobacco from locally made dry pipes whose design was familiar to an English observer, whereas men smoked cannabis in unfamiliar, antler-based water pipes. For example, a Vili proverb from s Cabinda counseled appropriate behavior: Cannabis, which objectively produces short-term memory loss and mental distraction, was the basis for mild insults.

Tobacco had greater commercial value, but was generally more expensive to produce, requiring fertile land and intensive labor. Cannabis could produce acceptably if grown on marginal land with little labor. Finally, tobacco came to the Sudanian region from across the Sahara. Arabic-language sources partly document dispersal into the western Sudan.

Most likely, English sailors introduced the plant and smoking to Morocco around ; tobacco and smoking arrived in Timbuktu Mali about with invading Moroccan troops. These terms likely derive from an Arabic term for snuff, but likely roots are undocumented in the Maghreb although shira meant smoked cannabis in 19th-century Tunisia. Snuff was the first form of tobacco consumption known in Iberian Europe, by , and Spanish soldiers were active in 16th-century Morocco.

The earliest documented debates in Africa were in Morocco and Timbuktu in the s. In Ethiopian Christianity, smoking was stigmatized as a pagan practice by the early s. Tobacco, and possibly cannabis, was consequently stigmatized. In the s, European travelers rarely noticed any smoking, though tobacco snuffing and chewing were common.

Modes of tobacco consumption varied historically and geographically. Tobacco and cannabis were often smoked in mixture, with proportions varying according to availability and taste. For instance, earlyth-century Maghrebian smokers mixed the plants though tobacco was disfavored, particularly in Morocco. Cannabis was not widely present or adopted until after World War II, despite its arrival in Sierra Leone and dispersal into neighboring areas by the s.

Mode of consumption varied too, among smoking, snuffing, and chewing. In Madagascar, for example, smoking was common in the s and s, but by the s snuffing was common and smoking rare. Instead, people held prepared snuff in the mouth. Manufactured cigarettes rapidly supplanted pipes worldwide after about Workers in cigarette factory, Ghana, Tobacco pipe smoking persisted widely in Africa into the mids, but cigarettes have become the strongly dominant form of tobacco consumption.

Tobacco was politically and economically significant almost immediately upon its arrival. Its trade value helped sustain European coastal commerce. Traders offered many goods, but tobacco and pipes proved particularly valuable at various places and times. African tobacco often outcompeted imports, thereby providing economic leverage to producing societies.

For instance, Yao society primarily Malawi and Mozambique gained wealth by shipping tobacco and other goods to coastal traders beginning in the s; this wealth helped facilitate their regional dominance especially in the s, when Yao tobacco remained highly valuable on the coast. Precolonial and colonial states in the Maghreb formally harnessed tobacco by establishing monopolies to tobacco and cannabis trades.

Tobacco has had a complicated relationship with slavery. In the United States, slave importation exploded in the s to sustain booming tobacco plantations; slave buyers sometimes paid directly with tobacco. Most notably, slave-grown tobacco from Bahia Brazil was preferred along the Slave Coast during the s and s. Brazilians controlled this tobacco trade and thus dominated slave buying.

Further, tobacco enhanced the endurance of laborers, thereby strengthening labor-intensive production systems. People worldwide have valued tobacco as a calming drug while working. The miners in front center are smoking, one a cigarette and the other a pipe, South Africa, between and Between and , photographic print, Library of Congress.

In 16th-century Morocco, tobacco may have initially flourished among slaves on English sugar plantations. Tobacco continues to enhance labor endurance in current societies, even if it has also long provided a calming pastime to elites. Producers across the continent relied upon slave labor well into the s to sustain adequate commercial supply.

Beginning in the late s, tobacco was a focal crop for colonial agricultural development efforts. Few African colonies established export industries. The United States dominated global tobacco production during the s, and African producers mostly supplied domestic and regional markets. Successful African industries mostly arose after this shift, using U. African tobacco products were not commercialized, although some industries started with indigenous varieties that suited European tastes. American seeds, however, were widely imported in the s.

Tobacco was important in white settler societies in East and Southern Africa. In Rhodesia, for instance, tobacco was among the earliest crops, and by the colony was committed to producing American-style tobacco. Tobacco commercialization and marketing increased after World War II and under postcolonial governments, leading to the development of iconic brands as well as smoking-induced public-health problems. Tobacco production in the United States has declined in recent decades, allowing farmers in Africa and elsewhere to increase their production and sales.

Simultaneously, tobacco consumption has decreased in the United States and Europe, which has caused international tobacco companies to seek markets elsewhere. Africa is particularly attractive because rates of tobacco use in most African countries are globally low among both men and women. Relevant literature on cannabis and tobacco is uneven, because tobacco has long been prominent worldwide, whereas cannabis has been less prominent and often purposefully concealed. The primary and secondary literature on tobacco in Africa is extensive, while that on cannabis is relatively thin.

Archival sources and non-European primary literatures are poorly known. Key published Arabic-language sources for cannabis and tobacco are known for North Africa, but this literature has not been thoroughly examined.

In This Article

The Abyssinian record is barely known; any Swahili primary documents are unknown. European primary sources for cannabis come principally from the s. Scattered earlier sources exist, but prior writers gave relatively little attention to cannabis drug use worldwide. Many European observers in Africa, however, did not know that cannabis supplied the observed drug; those who identified the plant considered its drug use a waste of a potentially valuable source of hemp fiber, the primary European value for cannabis.

European disdain for cannabis drug use, followed by colonial legal prohibition, pushed human—cannabis interactions into the undocumented underground increasingly over the s and almost entirely by Many published European travel accounts and botanical sources include brief mentions of cannabis; substantial descriptions are rare. Many accounts focus on smoking pipes, which provide only indirect information on cannabis and tobacco. Documents often do not use readily recognizable terms, but instead phonetic representations of African plant names, with highly variable spelling.

Key, substantial sources come from North Africa beginning in , Central Africa beginning in , and West Africa in Archival holdings relating to cannabis are poorly surveyed. Recent histories of Egypt, Sierra Leone, and Democratic Republic of Congo cite documents from police and judicial archives that mention cannabis; similar archives elsewhere likely also hold relevant primary sources from perhaps the s onward. Archival sources probably exist too for areas that had formal cannabis trades, particularly Morocco and Tunisia, but relevant collections are unknown.

Finally, some archives have ethnographic collections including images of smoking, such as the Diamang Digital archive at the University of Coimbra, Portugal, which includes earlyth-century materials from the area where the Bena Riamba were active. The primary literature on tobacco is very large. Most Europeans in Africa were ignorant of cannabis smoking into the early s, while very familiar with tobacco. Nonetheless, many published primary sources describe tobacco in Africa beginning about Most travel accounts and botanical sources from about include mentions or substantial discussions of tobacco; commercial records widely provide more or less detailed information on tobacco markets.

Most historical sourcebooks—collections of previously unpublished documents—include records of tobacco from across the continent for the 17th through 19th centuries. Colonial efforts to commercialize tobacco produced extensive documentation. National archives in many countries include documents on 20th-century tobacco industries, though few collections have been substantially studied. Globally, important sets of private commercial records have become public as a result of litigation against transnational tobacco companies in the United States.

Millions of documents from many companies are publicly available online in the Truth Tobacco Industry Documents archive at the University of California, San Francisco. This collection includes documents from British American Tobacco Company, which has been active widely in Africa since the early s. Many global histories of cannabis and tobacco mention Africa. However, most global histories were written for popular audiences and often show poor research methods and analyses. Professional researchers must be especially cautious with global histories of cannabis because prohibition has stunted research on the plant; inaccurate and unfounded historical anecdotes persist widely.

The history of cannabis in Africa has been scarcely researched. Several recent papers have provided narrowly specific case studies or broad overviews. Further, global histories of drugs also neglect Africa, including the best of these works. Many global histories of tobacco have been published since the mids that provide reliable overviews for Africa.

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