Current practice and recommendations for advancing how human variability and susceptibility are considered in chemical risk assessment

Table 3 Default and probabilistic approaches to intra-species adjustment for human variability and consideration of susceptible subgroups

Agency	TK Subfactor	TD Subfactor	Total Intra-species AF	Type	Subgroup Consideration
US EPA	√10 ≈ 3	√10 ≈ 3	10-fold	Default	Does not explicitly account for sensitive subgroups.
Cal EPA (OEHHA)	10	√10 ≈ 3	30-fold	Default	Children/infants and genetic TK susceptibility (though does not cover fetal period nor all identified variabilities).
IPCS/WHO	2–4.5^a	2.5–10^a	3.5–42-fold^a	Probabilistic	Does not explicitly account for sensitive subgroups; data based primarily on studies in healthy adults.

Intra-species adjustment (sub) factors representing human metabolism (TK) and tissue response (TD) TK/TD variability
^a IPCS ranges include median and 95th percentile estimates for target population incidence ranging from 1 to 10% [16]

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