Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale

Figures & data

Figure 1. Scientific evidence required for assessing the carcinogenic potential of a new food ingredient.

Figure 2. Chemical structure of sucralose.

Table 1. Sucralose and derivatives genotoxicity assays.

Test	Results	Reference
Gene mutation assays
In vitro Ames (reverse mutation)	Negative ± metabolic activation	Brusick et al. (63)
In vitro mouse lymphoma	Negative ± metabolic activation	Brusick et al. (63)
DNA damage and repair assays
In vitro DNA repair (E coli)	Negative ± metabolic activation	Brusick et al. (63)
In vitro DNA repair (F344 and rat hepatocytes)	Negative	Jeffery and Williams (70)
In vitro Comet	Positive in absence of activation	van Eyk (73)
In vivo Comet (mice)	DNA damage induced at 2,000 mg/kg body weight (24 h) in glandular stomach, colon, and lung tissue^a	Sasaki et al. (74)
Chromosome breakage/rearrangement assays
In vivo rat bone marrow chromosome aberration	Negative	Brusick et al. (63)
In vivo mouse micronucleus	Negative	Brusick et al. (63)
In vitro chromosome aberration assay (human lymphocytes)	Negative in absence of activation	Brusick et al. (63)

^a Following a review of the study data by Brusick et al. (63), it was determined that “positive results in the comet assay do not necessarily reflect carcinogenicity.”

Figure 3. Absorption, disposition, metabolism, and excretion of sucralose (44–48,86).

Table 2. Abbreviated animal model carcinogenicity studies—sucralose and sucralose hydrolysis products.

Test	Dose	Results
GLP rat feeding study, 2 yr duration Mann et al. (93) US FDA sucralose final rule (51)	0% (control), 0.3%, 1.0%, 3.0% sucralose in diet continuously   Exception: sucralose reduced to 1.0% maximum during lactation	No evidence of:   Effect on survival   Carcinogenic potential in adults or offspring   Neoplasia nor type, distribution, or multiplicity of tumor Sucralose treated rats had:   Non-neoplastic findings not unusual in aging rats   Lower body weight gain and food consumption than controls
GLP mouse feeding study, 2 yr duration Mann et al. (94) US FDA sucralose final rule (51)	0% (control), 0.3%, 1.0%, 3.0% in diet continuously	No evidence of:   Effect on survival, clinical condition, or behavior   Occurrence of tumors or benign neoplasms, malignant neoplasms, or total number of tumor bearing mice   Gross physical abnormalities Sucralose treated rats had:   Non-neoplastic findings not unusual in ageing mice   Erythrocyte counts 7–9% lower than controls in females receiving highest dose
Dog feeding study, 1 yr duration US FDA sucralose final rule (51) Goldsmith (87)	0.3%, 1.0%, 3.0% in diet continuously	No evidence of toxic effects at any dose Sucralose treated male dogs had Increase body weight gain accompanied by increased food consumption

Table 3. Epidemiology studies evaluating the effect of non-nutritive sweeteners on risk of cancers.

Test	Dose	Results
CPS II nutrition cohort: prospective study of cancer incidence and mortality in the US, 10 year follow up report McCollough et al. (96)	Daily consumption of sweetened beverages via recall Focus: use of aspartame	Consumers of ≥1 artificially or sugar sweetened beverages daily were not at higher risk for non-Hodgkins lymphoma or subtypes during 10-yr follow-up
Epidemiologic assessment of data from Nurses' Health Study and Health Professionals Follow-up Study analyzed over 22 yr Schernhammer et al. (97)	Consumption of sweetened beverages via recall   Focus: use of aspartame; other sweeteners not identified	Higher risk of non-Hodgkins lymphoma and multiple myeloma in men correlated with higher consumption of sugar sweetened soda In women, no associations between diet sodas and major types of non-Hodgkins lymphoma seen Some elevated risks associated with regular soda Potential carcinogenicity related to aspartame is biologically plausible due to: Chemical structure of parent and metabolic products Possible interactions between parent or metabolic products and DNA

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