Jj. Chen et S. Lensing, CAUSAL-MODELING OF MULTIVARIATE OUTCOMES FROM DEVELOPMENTAL TOXICITY EXPERIMENTS, Environmental and ecological statistics, 3(3), 1996, pp. 207-218
Exposure to developmental toxicants may cause foetal malformations, in
crease foetal death or resorption and reduce foetal weight. The correl
ations among these developmental endpoints have been reported, but the
ir causal relationships have not been investigated. Structural equatio
n models (path models) were applied to study the patterns of causation
among the four developmental outcomes, number of viable foetuses, num
ber of malformations, number of deaths/resorptions, and average foetal
weight; these outcomes were modelled as response variables with the d
ose level and number of implants (litter size) modelled as independent
variables. Three hypothesized path models were fitted to developmenta
l toxicity data from a study of the herbicide 2,4,5-T exposure in mice
. One model, which hypothesized that foetal weight, implicitly a mecha
nism such as cellular growth, affects both malformations and death/res
orption (equivalently, viability) with no causation relationship betwe
en malformation and death/resorption, described data consistently well
for three strains of mice. The most consistent relationship found was
a strong direct effect of foetal weight on malformations, and the cor
relation between malformations and death/resorption (or reduced viabil
ity) was likely spurious.