A safety factor of 100‐fold is commonly applied to animal data to derive the acceptable daily intake (ADI) of food additives; other factors have been used in some cases and higher values are used more frequently for determining the tolerable daily intake (TDI) of environmental chemicals. The 100‐fold factor is considered to represent the product of a 10‐fold factor to allow for species differences between the test animal and humans and a 10‐fold factor to allow for inter‐individual differences. A scheme is proposed whereby data relevant to the safety assessment of a compound, e.g. species differences in toxicokinetics, can contribute quantitatively to the safety factor and therefore to the ADI or TDI. For this to be possible, it is necessary to subdivide each of the 10‐fold factors into two separate factors to allow for differences in toxicokinetics and toxicodynamics. For any compound, data on one particular aspect may be used to derive a specific data‐derived factor for that aspect. The overall safety factor will then be calculated as the product of the known data‐derived factor(s) and default values for the remaining unknown factors. In this way the derivation of the safety factor would be clearly defined and the potential impact of additional data on other aspects identified. Additional safety factors (over and above the 100‐fold or overall data‐derived factor) are also proposed to allow for the nature or severity of the toxicity and the adequacy of the database. These factors are consistent with previous evaluations and will allow the logical derivation of factors greater than either 100 or the appropriate data‐derived factor. These additional factors will be of greatest value in the derivation of safety factors for the calculation of the TDIs of environmental contaminants but may also be applied if necessary to the safety assessment of food additives. In such cases the rationale and logic for a safety factor in excess of 100 will be clearly defined.