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Table 5 Quantitative evaluation on intraspecies differences between adult and the young

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

Substances dataset

Dose metric

Stage of development

Results

Reference

Animal data

238 chemicals

LD50

Adult and newborn mammals

Median LD50Adult/LD50Newborn = 2.6

[70]

   

14% of ratios exceeded 10

 

18 industrial chemicals

pNOAEL

Young and newborn rats (postnatal days 4 to 21)

NOAELYoung/NOAELNewborn < 5 for 17 of 18 chemicals

[98]

Human data

15 anticancer drugs

MTD

Adults and children

1.3 < Mean MTDChild/MTDAdult <4.1

[99], ratio of equivalent doses in mg/kg calculated by Dourson et al. [100]

24 drugs

Hepatic clearance (Cl) or half-life (HL)

Adults and newborns

Cl or HLNewborn/ Cl or HLAdult > 3.2 for 33% of drugs

[101], ratios calculated by Dourson et al. [100]

22 substances

Toxicokinetic parameters

Adults and children and/or newborns

3.2 subfactor for toxicokinetics intraspecies differences adjusts the adult parameter to that of the infant or child for 91% of substances.

[78] as calculated by Dourson et al. [100]

313 substances (mostly pharmaceuticals)

LD50

Adults and children

14% of LD50Adult/LD50Child > 10

[102]

6 drugs

Toxicokinetic parameters (one toxicodynamic)

Adult and children

Ratio of mean adult parameter to lower 95% value of children varied between 0.6-3.7.

[92]

   

Composite ratios all below 10

 

44 drugs

Half-life

Adult and children in different age groups

Proportion of children whose half-life exceed 3.2-fold the adult mean value;

[94]

   

0–1 week premature: 70%

 
   

0–1 week full term: 26%

 
   

1 week- 2 months: 27%

 
   

2 months-18 years: 0%