3 research outputs found
Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice
6:2 fluorotelomer alcohol (6:2 FTOH) was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100Â mg/kg/day. The no-observed-adverse-effect level (NOAEL) for systemic toxicity was 25Â mg/kg/day (males) and 5Â mg/kg/day (females), based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell), clinical chemistry (liver-related), liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland). However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100Â mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25Â mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100Â mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5Â mg/kg/day for systemic toxicity and 25Â mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals
Safety Assessment of Food and Feed from GM Crops in Europe: Evaluating EFSA’s Alternative Framework for the Rat 90-day Feeding Study
Regulatory-compliant
rodent subchronic feeding studies are compulsory
regardless of a hypothesis to test, according to recent EU legislation
for the safety assessment of whole food/feed produced from genetically
modified (GM) crops containing a single genetic transformation event
(European Union Commission Implementing Regulation No. 503/2013).
The Implementing Regulation refers to guidelines set forth by the
European Food Safety Authority (EFSA) for the design, conduct, and
analysis of rodent subchronic feeding studies. The set of EFSA recommendations
was rigorously applied to a 90-day feeding study in Sprague–Dawley
rats. After study completion, the appropriateness and applicability
of these recommendations were assessed using a battery of statistical
analysis approaches including both retrospective and prospective statistical
power analyses as well as variance–covariance decomposition.
In the interest of animal welfare considerations, alternative experimental
designs were investigated and evaluated in the context of informing
the health risk assessment of food/feed from GM crops