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Table 6 Probabilistic multiplication of subfactors

From: Dispelling urban myths about default uncertainty factors in chemical risk assessment – sufficient protection against mixture effects?

Reference Database used Distribution parameters Results
Sheehan et al. 1990 [70]
Interspecies variation Ratios of tumour incidences (TD50s) for 190 chemicals in mice and rats Median = 2.6  
Intraspecies variation Ratios of acute lethality (LD50s) for adult and newborn mammals for 238 chemicals Median = 2.4  
Overall assessment    Values exceeding 100: 11.8% predicted, 10% observed
Baird et al. 1996 [107]
Interspecies variation 69 pesticides tested in different animal species, allometrically adjusted for body surface (Dourson et al. 1992) Median = AS1  
   GSD = 5  
Intraspecies variation Probit dose–response slopes from 490 acute lethality experiments using rats [75], assuming two different levels of protection; Basic approach:  
   Median = 2.7  
   GSD = 2.3  
  Basic approach: 1/100,000 Alternative approach:  
  Alternative approach: 1/1,000 Median = 5.3  
   GSD = 1.4  
Overall assessment RfDs or RfCs for 126 compounds with NOAELs from chronic bioassays in IRIS database Basic approach: Fraction of RfDs within the lower 5% of distribution of potential threshold values2 ;
   Median = AS x 3 All: 56%
   P95 = AS x 50 Mice: 23%
   P99 = AS x 220 Rats: 39%
   Alternative approach: Dogs: 98%
   Median = AS x 5  
   P95 = AS x 63  
   P99 = AS x 194  
Vermeire et al. 1999 ; Vermeire et al. 2001 [5, 49]
Interspecies variation 184 substances tested in mice, rats and dogs GM = AS Factor 12 (4 for allometric scaling x 3 for remaining uncertainty) coincides with 73rd percentile.
   GSD = 4.5  
   P95 = AS x 19  
   P99 = AS x 65  
Intraspecies variation Theoretical, to be consistent with default factor 10, P99 = 10 [108] Median = 1 + 3  
   GSD = 1.6  
Overall assessment   GM = AS x 4 Percentile of the default factor 100: 79% (NOAEL in mouse), 88% (NOAEL in rat)3
   GSD = 4.7  
   P95 = AS x 53  
Gaylor and Kodell 2000 [109]
Interspecies variation Binary aquatic interspecies comparisons from dozens to over 500 agents [72] Median = 1  
   GSD = 1.66  
Intraspecies variation Probit dose–response slopes from 490 acute lethality experiments using rats [75] adapted by Dourson and Stara [31] Median = 1 Default value of 10 corresponds to the 92nd percentile
   GSD = 1.64  
Overall assessment   Median = 1  
   GSD = 2.33  
   P95 = 46  
   P99 = 230  
Schneider et al. 2005 [106]
Interspecies variation 63 antineoplastic agents in humans and five different animal species [68] GM = AS x 0.97  
   GSD = 3.45  
   P95 = AS x 6.7  
   P99 = AS x 15  
Intraspecies variation Human database for predominantly healthy adults developed by Hattis et al. [79] GM = 3.8  
   GSD = 4.3  
   P95 = 44  
   P99 = 117  
Overall assessment Our own calculation GM = AS x 3.7 Proportion of substances for which the default factor 100 would not be exceeded:
   GSD = 5.4 AS based on caloric demand; 76% (mouse), 85% (rat)
   P95 = AS x 82 AS based on surface area; 64% (mouse), 79% (rat)
   P99 = AS x 295  
Hasegawa et al. 2010 [110]
Interspecies variation 63 antineoplastic agents in humans and five different animal species adapted from [68] GM = AS  
   GSD = 3.23  
   P95 = 48.2 (mice)  
   P95 = 27.5 (rats)  
Intraspecies variation Rat young/newborn NOAEL ratios for 18 industrial chemicals [98] GM = 3  
   GSD = 1.38  
   P95 = 5.09  
Overall assessment   P95 = 155 (mice)  
   P95 = 88.7 (rats)  
  1. References
  2. 1 Allometric scaling factor according to body surface area (mouse = 14, rat = 6).
  3. 2 For 231 RfDs including some derived from LOAELs and/or sub-chronic bioassays.
  4. 3 Allometric scaling factors based on caloric demand were used.