Table 3.

Adequacy evaluation criteria for individual animal studies on the potential carcinogenicity of nicotine.

Category	Adequate study parameters
Route of administration	Inhalation, oral, dermal
Group size	50 per sex (100 of single sex)
Dose–response	Three (or two) dose levels
Daily dose (average)	Eliciting signs of toxicity, or
	≥1 mg/(kg × d)
Duration of exposure	≥18 months (complete carcinogen studies)
	Any duration (modulating carcinogenesis studies)
Quality (subjective)	e.g., Nicotine biomonitoring, body weight data

Notes:

(1) Adequacy criteria for group size, dose–response, and study duration were derived from the carcinogenicity study design guidance provided by the Organisation for Economic Co-operation and Development (2009). Other adequacy criteria were subjectively set by the authors.

(2) Adequacy was scored with plus (+) or minus (−). If information was lacking, minus (−) was also applied.

(3) Plus (+) scores of a study were totaled for an overall adequacy score. The maximum plus (+) score is 6 (studies on complete carcinogenesis) or 5 (modulating studies), with >2(+) representing a high-adequacy score and ≤2(+) representing a low-adequacy score.