J. C. Larsen

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

The CALUX (chemically activated luciferase expression) bioassay based on rat hepatoma (H4IIE) cells is a sensitive assay for the detection of Ah receptor agonists like 2,3,7,8-substituted chlorinated dibenzo-p-dioxins and dibenzofurans and related PCBs. In this paper, the assay was optimized and applied for monitoring levels of dioxins in human milk samples. Combination effects of dioxin-like compounds were evaluated by testing potential mechanisms of interaction between seven of the major dioxin-like compounds in human milk using the isobole method. Results showed that the compounds acted additively, indicating that the usual assumption of additivity in the risk assessment process is valid. In general the relative potencies (REPs) of the single agents were in accordance with their TEFs assigned by the World Health Organisation, except for the mono-ortho-substituted PCB118 that had a 40-fold lower REP in CALUX. The total dioxin-like activity was determined in 16 Danish human milk samples and was in the range 20.5-55.8 pg TEQ g(-1) fat. These values were compared with TEQs obtained from GC/MS analysis (range 14.8-43.6 pg TEQ-g(-1) fat) that overall were a little lower than CALUX TEQs. The results obtained with the bioassay when testing milk extracts fractionated into dioxins/furans, non-ortho PCB and mono/di-ortho PCB fractions indicated that the correlation between the bioassay and the chemical analyses depends primarily on the Ah receptor activity observed in the mono/di-ortho PCB fraction.

Polyoxyethylene alkylphenols (PA) are a group of non-ionic surfactants with a widespread use. As part of the safety evaluation of PA a teratology study with nonoxynol-9 and -30 (NP-9 and NP-30) administered perorally and epicutaneously to rats was performed. In addition the mutagenicity of NP-9 was tested in the Ames test. Treatment of pregnant rats with NP-30 (up to 1 g/kg b.wt./day, orally) did not reveal any signs of adverse effects. Pregnant rats given 250 mg or 500 mg NP-9/kg b.wt./day orally exhibited a statistically significant decrease in weight gain. A concomitant effect in these dams on reproduction, and an increase in the incidence of extra ribs and dilated pelvic cavity in their foetuses was interpreted as a consequence of a toxic effect of high doses of NP-9. No clear cut effect was observed when pregnant rats were dosed epicutaneously with up to 500 mg of NP-9/kg b.wt./day. A slight but persistent response in one tester strain in the Ames test was not interpreted as a clear mutagenic effect of NP-9.