Haighton · Regulatory toxicology and pharmacology : RTP 2019 · systematic review of animal bioassays · n=9 studies

Systematic review and evaluation of aspartame carcinogenicity bioassays using quality criteria.

Cited 22 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Systematic review of animal carcinogenicity bioassays without human data

PubMed 29339245 · doi:10.1016/j.yrtph.2018.01.009 · record verified 2026-08-31

What was done

A systematic review evaluated the quality of animal cancer bioassays of aspartame using the Klimisch grading system. Nine studies with complete histopathology were appraised: three 2-year studies by Searle, three transgenic mice studies by the National Toxicology Program (NTP), and three lifetime studies by the Ramazzini Institute. A tenth study restricted to brain tumors was not rated.

What was found

Zero studies met the criteria for Klimisch Code 1 (reliable without restrictions). Six studies were rated Klimisch Code 2 (reliable with restrictions): three pre-GLP Searle studies and three NTP transgenic mouse studies, which demonstrated no carcinogenic potential. The three Ramazzini Institute lifetime studies were rated Klimisch Code 3 (not reliable) due to high background rates of spontaneous tumors in animals dying near end of life, tumor diagnostic concerns, and chronic infections. No numerical risk ratios or tumor counts were provided in the abstract.

Why it matters

The paper contextualizes contradictory rodent cancer data on aspartame by attributing positive carcinogenicity findings to methodological weaknesses in lifetime animal protocols.

Limits

The review evaluates rodent bioassays rather than human health outcomes. None of the included animal studies achieved top-tier reliability (Klimisch Code 1), and quantitative effect estimates were not reported in the abstract.

Cited by