Subchronic Toxicity of Baltic Herring Oil and its Fractions in the Rat II: Clinical Observations and Toxicological Parameters

Abstract

This study aimed to increase the knowledge about the toxicity of fish-derived organohalogen pollutants in mammals. The strategy chosen was to separate organohalogen pollutants derived from Baltic herring (Clupea harengus) fillet, in order to obtain fractions with differing proportions of identified and unidentified halogenated pollutants, and to perform a subchronic toxicity study in rats, essentially according to the OECD guidelines, at three dose levels. Nordic Sea lodda (Mallotus villosus) oil, with low levels of persistent organohalogen pollutants, was used as an additional control diet. The toxicological examination showed that exposure to Baltic herring oil and its fractions at dose levels corresponding to a human intake in the range of 1.6 to 34.4 kg Baltic herring per week resulted in minimal effects. The spectrum of effects was similar to that, which is observed after low-level exposure to pollutants such as chlorinated dibenzo-p-dioxins and dibenzofurans (CDD/F) and chlorinated biphenyls, despite the fact that these contaminants contribute to a minor part of the extractable organically bound chlorine (EOCl). The study confirmed previous findings that induction of hepatic ethoxyresorufin deethylase (EROD) activity takes place at daily intake levels 0.15 ng fish-derived CDD/F-TEQs/kg body weight. The study also demonstrated that hepatic vitamin A reduction takes place at somewhat higher daily exposure levels, i.e. 0.16-0.30 ng fish-derived CDD/F-TEQs/kg body weight. Halogenated fatty acids, the major component of EOCl, could not be linked to any of the measured effects. From a risk management point of view, the study provides important new information of effect levels for Ah-receptor mediated responses following low level exposure to organohalogen compounds from a matrix relevant for human exposure.

Subchronic Toxicity of Baltic Herring Oil and its Fractions in the Rat (III) Bone Tissue Composition and Dimension, and Ratio of n‐6/n‐3 Fatty Acids in Serum Phospholipids

“…The fat concentration in the R34 diet is standardised to 3.5 % (mainly fish fat). 2 The daily consumption of CDD/F‐TEQ, calculated according to WHO‐TEF (Van den Berg et al 1998), was estimated from the contaminant concentrations in herring oil and its fractions (Öberg et al 2002), the fish fat content of the diets and the estimated daily food consumption (Stern et al 2002). …”

“…Due to the concern of health effects of various organohalogen pollutants, including dioxins and PCBs in fatty fish, a subchronic toxicity study was carried out in the rat (Stern et al 2002; Öberg et al 2002). Rats were given Baltic herring oil or its fractions at different doses in the diet to examine the contribution of different organohalogen pollutants to toxicity and biological effects.…”

“…We reported that CYP1A1 induction and hepatic Vitamin A depletion could be related to pollutants such as PCDD/Fs and PCBs, despite the fact that these compounds contribute on a weight basis to a minor part of the extractable organically bound chlorine (Öberg et al 2002). We have also reported changes in total bone mineral density (determined by the bone‐ash method) in rats exposed to Baltic Herring oil or its fractions (Stern et al 2002). More detailed follow‐up analysis of single bones showed dramatic differences in bone composition between some dietary groups.…”

“…The underlying mechanisms for the observed effects on bone tissue, however, are still unclear. In an attempt to address this question, we extended our previous study on rats (Stern et al 2002) by using the more sophisticated bone investigation method of peripheral quantitative computed tomography (pQCT). In addition, we attempted to evaluate any casual relationships between the observed bone effects and the exposure to chemical pollutants on the one hand and natural food components on the other hand.…”

Risks and Management of Dioxins and Dioxin-like Compounds in Baltic Sea Fish: An Integrated Assessment

“…1996b;c van der Plas & al. 2001; Stern & al. 2002; e f RCMV=rat cytomegalovirus; g NK=Natural Killer cell.…”