Table 2.

In Vitro Toxicity of Oral Nicotine Pouches Compared to Other Tobacco Products

Author, yearFundingTest productToxicity: ONPToxicity: Reference product 1Toxicity: Reference product 2
Bishop et al., 202068BATLYFT, Berry Frost 4 mgMinimal cytotoxicity in all assaysSnus
Minimal to moderate cytotoxicity in all assays
Cigarette
Consistent toxicological effects in most assays
East et al., 202169BATLYFT, 4–11 mg, various flavorsAll deemed non-cytotoxic (below the 30% toxicity threshold)Competitor ONP (Nordic Spirit)
86% toxicity
Snus
91% toxicity
Yu et al., 202270Imperial BrandsSkruf Superwhite (mint, 5.8 and 10.1 mg)Minimal cytotoxicity (above the 20% toxicity threshold)Snus
Minimal to moderate cytotoxicity (above the 20% toxicity threshold)
Cigarette
Substantially more cytotoxic
Alizadehgharib et al., 202271Swedish MatchZYN (cinnamon, smooth, peppermint, 3 or 6 mg)No inflammatory responseCompetitor ONP
(LYFT Ice Cool)
Significant increase in the production of proinflammatory cytokines
Four snus products
Significant increase in the production of proinflammatory cytokines
Shaikh et al., 202272U.S. National Institutes of HealthMultiple nicotine strengths of different flavor ONPs (ZYN, ON!, VELO, and Rogue)Increased cytotoxicity and inflammatory response compared to non-treated cellsSnus
Cytotoxic effects of ZYN spearmint were comparable to those of identically flavored reference snus product.
Shaikh et al., 202273U.S. National Institutes of HealthZYN Smooth 6 mg, Lucy Spearmint 8 mg, ON! 8 mg CitrusIncreased cytotoxic response for ON! (20%–34%) and Lucy (13%–19%) at all concentrations, and ZYN (15%–30%) at higher concentrations.Snus
Increased cytotoxic response of 13%–16% at higher concentrations for snus #1, and 21%–27% at all concentrations for snus #2.
Miller-Holt et al., 202274JTINordic spirit spearmint and mint of multiple strengthsnon-mutagenic, non-genotoxic and non-cytotoxicSnus
non-mutagenic, non-genotoxic and non-cytotoxic
Cigarettes
mutagenic, genotoxic, and cytotoxic
Rinaldi et al., 202375FederalFive ONPs of various flavors and nicotine strengthsCytotoxicity was observed in two of the five ONPs.Snus
No cytotoxicity
Author, yearFundingTest productToxicity: ONPToxicity: Reference product 1Toxicity: Reference product 2
Bishop et al., 202068BATLYFT, Berry Frost 4 mgMinimal cytotoxicity in all assaysSnus
Minimal to moderate cytotoxicity in all assays
Cigarette
Consistent toxicological effects in most assays
East et al., 202169BATLYFT, 4–11 mg, various flavorsAll deemed non-cytotoxic (below the 30% toxicity threshold)Competitor ONP (Nordic Spirit)
86% toxicity
Snus
91% toxicity
Yu et al., 202270Imperial BrandsSkruf Superwhite (mint, 5.8 and 10.1 mg)Minimal cytotoxicity (above the 20% toxicity threshold)Snus
Minimal to moderate cytotoxicity (above the 20% toxicity threshold)
Cigarette
Substantially more cytotoxic
Alizadehgharib et al., 202271Swedish MatchZYN (cinnamon, smooth, peppermint, 3 or 6 mg)No inflammatory responseCompetitor ONP
(LYFT Ice Cool)
Significant increase in the production of proinflammatory cytokines
Four snus products
Significant increase in the production of proinflammatory cytokines
Shaikh et al., 202272U.S. National Institutes of HealthMultiple nicotine strengths of different flavor ONPs (ZYN, ON!, VELO, and Rogue)Increased cytotoxicity and inflammatory response compared to non-treated cellsSnus
Cytotoxic effects of ZYN spearmint were comparable to those of identically flavored reference snus product.
Shaikh et al., 202273U.S. National Institutes of HealthZYN Smooth 6 mg, Lucy Spearmint 8 mg, ON! 8 mg CitrusIncreased cytotoxic response for ON! (20%–34%) and Lucy (13%–19%) at all concentrations, and ZYN (15%–30%) at higher concentrations.Snus
Increased cytotoxic response of 13%–16% at higher concentrations for snus #1, and 21%–27% at all concentrations for snus #2.
Miller-Holt et al., 202274JTINordic spirit spearmint and mint of multiple strengthsnon-mutagenic, non-genotoxic and non-cytotoxicSnus
non-mutagenic, non-genotoxic and non-cytotoxic
Cigarettes
mutagenic, genotoxic, and cytotoxic
Rinaldi et al., 202375FederalFive ONPs of various flavors and nicotine strengthsCytotoxicity was observed in two of the five ONPs.Snus
No cytotoxicity

BAT = British American Tobacco; JTI = Japan Tobacco International.

Table 2.

In Vitro Toxicity of Oral Nicotine Pouches Compared to Other Tobacco Products

Author, yearFundingTest productToxicity: ONPToxicity: Reference product 1Toxicity: Reference product 2
Bishop et al., 202068BATLYFT, Berry Frost 4 mgMinimal cytotoxicity in all assaysSnus
Minimal to moderate cytotoxicity in all assays
Cigarette
Consistent toxicological effects in most assays
East et al., 202169BATLYFT, 4–11 mg, various flavorsAll deemed non-cytotoxic (below the 30% toxicity threshold)Competitor ONP (Nordic Spirit)
86% toxicity
Snus
91% toxicity
Yu et al., 202270Imperial BrandsSkruf Superwhite (mint, 5.8 and 10.1 mg)Minimal cytotoxicity (above the 20% toxicity threshold)Snus
Minimal to moderate cytotoxicity (above the 20% toxicity threshold)
Cigarette
Substantially more cytotoxic
Alizadehgharib et al., 202271Swedish MatchZYN (cinnamon, smooth, peppermint, 3 or 6 mg)No inflammatory responseCompetitor ONP
(LYFT Ice Cool)
Significant increase in the production of proinflammatory cytokines
Four snus products
Significant increase in the production of proinflammatory cytokines
Shaikh et al., 202272U.S. National Institutes of HealthMultiple nicotine strengths of different flavor ONPs (ZYN, ON!, VELO, and Rogue)Increased cytotoxicity and inflammatory response compared to non-treated cellsSnus
Cytotoxic effects of ZYN spearmint were comparable to those of identically flavored reference snus product.
Shaikh et al., 202273U.S. National Institutes of HealthZYN Smooth 6 mg, Lucy Spearmint 8 mg, ON! 8 mg CitrusIncreased cytotoxic response for ON! (20%–34%) and Lucy (13%–19%) at all concentrations, and ZYN (15%–30%) at higher concentrations.Snus
Increased cytotoxic response of 13%–16% at higher concentrations for snus #1, and 21%–27% at all concentrations for snus #2.
Miller-Holt et al., 202274JTINordic spirit spearmint and mint of multiple strengthsnon-mutagenic, non-genotoxic and non-cytotoxicSnus
non-mutagenic, non-genotoxic and non-cytotoxic
Cigarettes
mutagenic, genotoxic, and cytotoxic
Rinaldi et al., 202375FederalFive ONPs of various flavors and nicotine strengthsCytotoxicity was observed in two of the five ONPs.Snus
No cytotoxicity
Author, yearFundingTest productToxicity: ONPToxicity: Reference product 1Toxicity: Reference product 2
Bishop et al., 202068BATLYFT, Berry Frost 4 mgMinimal cytotoxicity in all assaysSnus
Minimal to moderate cytotoxicity in all assays
Cigarette
Consistent toxicological effects in most assays
East et al., 202169BATLYFT, 4–11 mg, various flavorsAll deemed non-cytotoxic (below the 30% toxicity threshold)Competitor ONP (Nordic Spirit)
86% toxicity
Snus
91% toxicity
Yu et al., 202270Imperial BrandsSkruf Superwhite (mint, 5.8 and 10.1 mg)Minimal cytotoxicity (above the 20% toxicity threshold)Snus
Minimal to moderate cytotoxicity (above the 20% toxicity threshold)
Cigarette
Substantially more cytotoxic
Alizadehgharib et al., 202271Swedish MatchZYN (cinnamon, smooth, peppermint, 3 or 6 mg)No inflammatory responseCompetitor ONP
(LYFT Ice Cool)
Significant increase in the production of proinflammatory cytokines
Four snus products
Significant increase in the production of proinflammatory cytokines
Shaikh et al., 202272U.S. National Institutes of HealthMultiple nicotine strengths of different flavor ONPs (ZYN, ON!, VELO, and Rogue)Increased cytotoxicity and inflammatory response compared to non-treated cellsSnus
Cytotoxic effects of ZYN spearmint were comparable to those of identically flavored reference snus product.
Shaikh et al., 202273U.S. National Institutes of HealthZYN Smooth 6 mg, Lucy Spearmint 8 mg, ON! 8 mg CitrusIncreased cytotoxic response for ON! (20%–34%) and Lucy (13%–19%) at all concentrations, and ZYN (15%–30%) at higher concentrations.Snus
Increased cytotoxic response of 13%–16% at higher concentrations for snus #1, and 21%–27% at all concentrations for snus #2.
Miller-Holt et al., 202274JTINordic spirit spearmint and mint of multiple strengthsnon-mutagenic, non-genotoxic and non-cytotoxicSnus
non-mutagenic, non-genotoxic and non-cytotoxic
Cigarettes
mutagenic, genotoxic, and cytotoxic
Rinaldi et al., 202375FederalFive ONPs of various flavors and nicotine strengthsCytotoxicity was observed in two of the five ONPs.Snus
No cytotoxicity

BAT = British American Tobacco; JTI = Japan Tobacco International.

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