US EPA

1715166 

Journal Article 

Developmental Toxicology In The Neonatal Mouse: The Use Of Randomly Selected Individuals As Statistical Unit Compared To The Litter In Mice Neonatally Exposed To Pbde 99 

Eriksson, P; Von Rosen, D; Viberg, H; Fredriksson, A 

2005 

1 

Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 

TOX/5001208 

84 

1-S 

English 

In traditional behavioural teratology and/or developmental toxicology the chemical to be tested is given to the mother. The exposure period can include both the gestational and lactation period. In such a case the litter generally should be considered the statistical unit. In several reports we have shown that low-dose exposure of environmental toxic agents such as PCB, DDT, brominated flame-retardants, pyrethroids, organophosphates, and nicotine, can cause persistent developmental neurotoxic effects when administered directly to pups during a defined critical period of neonatal brain development in the mouse. In the present study the use of the litter or randomly selected individuals as a statistical unit in developmental toxicology in the neonate is evaluated. In this investigation 18 different litters were used. Pregnant NMRI mice were randomly selected and purchased from a commercial breeder. Male pups at the age of 10 days were given either one single oral dose of the brominated flame-retardant, 2, 2', 4, 4', 5-pentabromo diphenyl ether (PBDE 99) 1.4 umol/kg bw, or a vehicle (20% fat emulsion). Spontaneous motor behaviour was studied in 2-month-old-mice. Statistical evaluation was made by both using the litter (n=9) as a statistical unit and randomly selected individuals (n=9, 3 mice randomly selected from 3 different litters). Both statistical evaluations, using ANOVA, showed a significant deranged behaviour in the PBDE 99 exposed mice compared to controls, defects that we earlier have reported on. This study shows that there is no difference whether the litter or the randomly selected individuals are used as the statistical unit. This study also shows that randomly selected animals from different litters (at least 3) have the same statistical effect and power compared to the use of litter based studies to evaluate developmental neurotoxicity in neonatal mice.