Is current risk assessment of non-genotoxic carcinogens protective?

Non-genotoxic carcinogens (NGTXCs) do not cause direct DNA damage but induce cancer via other mechanisms. In risk assessment of chemicals and pharmaceuticals, carcinogenic risks are determined using carcinogenicity studies in rodents. With the aim to reduce animal testing, REACH legislation states that carcinogenicity studies are only allowed when specific concerns are present; risk assessment of compounds that are potentially carcinogenic by a non-genotoxic mode of action is usually based on subchronic toxicity studies.

An integrative test strategy for cancer hazard identification.

Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association between the accumulation of genetic damage and cancer. Using genotoxicity assays to predict carcinogenic potential has the significant drawback that risks from non-genotoxic carcinogens remain largely undetected unless carcinogenicity studies are performed.

Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4.

Background: Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor (TLR)-4 mediated mechanism. We hypothesized that effects of parenteral MCTs on immune cells involve TLR-4 signaling and that these effects are modulated by n-3 FA that are present in FO.

No Clinical or Biochemical Evidence for Essential Fatty Acid Deficiency in Home Patients Who Depend on Long-Term Mixed Olive Oil- and Soybean Oil-Based Parenteral Nutrition.

Background: Home parenteral nutrition (HPN) patients depend on lipid emulsions as part of their parenteral nutrition regimen to provide essential fatty acids (EFAs). Mixed-oil sources are used in modern lipid emulsions to decrease the amount of proinflammatory EFAs, mainly linoleic acid, which is present in large amounts in soybean oil. It is unknown whether patients who fully depend on such mixed lipids have adequate EFA supply.