19 research outputs found
Programming of metabolic effects in C57BL/6JxFVB mice by in utero and lactational exposure to perfluorooctanoic acid
Perfluorooctanoic acid (PFOA) is known to
cause developmental toxicity and is a suggested endocrine
disrupting compound (EDC). Early life exposure
to EDCs has been implicated in programming of the
developing organism for chronic diseases later in life.
Here we study perinatal metabolic programming by
PFOA using an experimental design relevant for human
exposure. C57BL/6JxFVB hybrid mice were exposed
during gestation and lactation via maternal feed to
seven low doses of PFOA at and below the NOAEL
used for current risk assessment (3–3000 μg/kg body
weight/day). After weaning, offspring were followed
for 23–25 weeks without further exposure. Offspring
showed a dose-dependent decrease in body weight from
postnatal day 4 to adulthood. Growth under high fat
diet in the last 4–6 weeks of follow-up was increased
in male and decreased in female offspring. Both sexes
showed increased liver weights, hepatic foci of cellular
alterations and nuclear dysmorphology. In females, reductions in perigonadal and perirenal fat pad weights,
serum triglycerides and cholesterol were also observed.
Endocrine parameters, such as glucose tolerance, serum
insulin and leptin, were not affected. In conclusion,
our study with perinatal exposure to PFOA in mice
produced metabolic effects in adult offspring. This is
most likely due to disrupted programming of metabolic
homeostasis, but the assayed endpoints did not provide
a mechanistic explanation. The BMDL of the programming
effects in our study is below the current point of
departure used for calculation of the tolerable daily
intake.The authors wish to acknowledge the support of
the biotechnicians from the team of Hans Strootman at the RIVM animal
facilities. Further technical support was provided by Piet Beekhof,
Hennie Hodemaekers, Sandra Imholz (RIVM), Mirjam Koster
(UU), Stefan van Leeuwen (RIKILT), Jacco Koekkoek and Marja
Lamoree (VU). This study was funded by the European Community’s
Seventh Framework Programme [FP7/2007–2013] under grant agreement
OBELIX 227391
Risk, Uncertainty and Precaution in Science: The Threshold of the Toxicological Concern Approach in Food Toxicology
ISSN:1353-3452ISSN:1471-554