Table 2 Examples of increased susceptibility in the human population
Factor | Example | Susceptibilitya | Reference |
|---|---|---|---|
Examples from Science and Decisions 2009 report | |||
Genetic | Increased copper susceptibility among Wilson’s heterozygotes (~ 1% population). | > 10:1 | NRC 2000 [78] |
Predisposing exposure | Increased susceptibility among smokers to arsenic-induced lung cancer. | 20:1 | CDHS 1990 [76] |
Increased susceptibility among smokers to radon-associated lung cancer. | 10–20:1 | ATSDR 1992 [79] | |
Increased susceptibility among low-iodide female smokers to perchlorate-induced thyroid hormone disruption. | 20–100:1 | Blount et al. 2006 [77] | |
Preexisting disease | Increased susceptibility among people with hepatitis to liver cancer from aflatoxin. | 10–30:1 | Wu-Williams et al. 1992 [80] |
Physiologic and Pharmacokinetic | Difference in susceptibility to 4-aminobiphenyl (median vs upper 2 percentile) due to physiologic and pharmacokinetic differences (modeled). | > 10:1 | Bois et al. 1995 [81] |
Overall | Increased heterogeneity in lung and colorectal cancer risk (95th percentile vs median) from age-specific incidence curves. | 50:1 | |
Additional examples identified from peer-reviewed literature | |||
Age/life stage | Analysis of kinetic data from pharmaceutical studies in populations of adult white, non-white, children, and those with metabolic polymorphisms which found 10-fold variation (99.9% protective) too low for very young. | > 10:1 | Renwick and Lazarus 1998 [84] |
Greater susceptibility among elderly populations compared to adults. | > 10:1 | Abdel-Megeed 2001 [85], Skowronski et al. 2001 [86] | |
Under-protective of children. | > 10:1 | Hattis et al. 2002 [87] | |
Decreased expression or activity of xenobiotic metabolizing enzymes (e.g., cytochrome p450) in 2nd trimester fetal livers compared to adult livers. | 77–12,271:1 | Robinson et al. 2020 [88] | |
Age/life stage and genetic | Not protective of neonates, elderly, or people with polymorphisms. | > 10:1 | Dorne et al. 2007 [89] |
Increased TK susceptibility among children/infants and occupational groups with genetic susceptibility. | 1 to 30–60:1 | OEHHA 2008 [90] | |
Toxicokinetic | Increased variation in metabolic clearance of trichloroethylene (TCE). | 10–100:1 | Chiu et al. 2014 [91] |
Toxicodynamic | Increased variation in cytotoxic response to specific chemicals in population-based human in vitro models (95th percentile vs median) using 1000 Genomes Project. | 1 to 10–100:1 | Abdo et al. 2015a [92] |