LETTER TO THE EDITOR

Per Eriksson and Henrik Viberg

Department of Environmental Toxicology, Uppsala University, Norbyvägen 18 A, S-752 36 Uppsala, Sweden

To the Editor:

Regarding the "Letter to the Editor" from Drs. Henk P. M. Vijverberg and Martin van den Berg concerning our article "Neurobehavioural derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development" we were very pleased that the misprint in the table was observed. It should show pmol, as given in the text.

The letter from Vijverberg and van den Berg discusses the content of PBDE 209 in the mouse brain, in relation to levels found in human tissues, and whether environmental exposure to PBDEs can lead to high tissue concentrations; furthermore, whether PBDEs can induce specific neurotoxic effects and effects related to the degree of halogenation. They have compared the structure activity relation of PCB toxicity via Ah receptor induced toxicity. From the aforegoing, they question whether this paper is of any value for risk assessment.

We do agree on several points in the letter, especially that more knowledge about mechanisms is needed to form a firm basis from which to predict possible toxic effects of certain compounds. However, we have the opinion that any potentially toxic agent that is known to be increasing in our environment—and especially in mother's milk—should be of particular concern.

Identification of different PBDE congeners—and also possible metabolites—in our environment is still an ongoing work. New information is being gathered and improved analyses for such agents are continuously being developed.

Toxicity data on highly brominated diphenyl ethers are very sparse. Previously it was believed that the decabrominated diphenyl ether, PBDE 209, is not present in our environment and also assumed not to be taken up in an organism. However, our paper showed that mammals can take up PBDE 209. After oral administration of 14C-labelled PBDE 209 (uniformly labeled), radioactivity was detected in the mouse brain, heart, and liver. Whether it was the parent compound or its metabolites (including debrominated metabolites) could not be said. Regarding the time for when the compound was given to the neonatal animals and the development of neurotoxic effect it is suggested that a metabolite was the agent responsible for the observed effects (doses, time of administration, and effects—in relation to radioactivity found in the brain—are discussed in the paper). PBDE 209 is also found in human blood (Jakobsson et al., 2002Go). The question calls for an answer: is this of importance when estimating the risk of PBDEs and/or PBDE 209?

With regard to our earlier studies on developmental neurotoxic effects of certain PCBs, we have reported that some ortho-substituted and some coplanar PCBs do indeed cause observed developmental neurotoxic effects such as deranged spontaneous behavior, diminished or lack of habituation to a novel environment, and learning and memory defects (Eriksson, 1998Go). We have also found that the cholinergic system is one target that is affected, observed as changes in the response of the cholinergic system and a decrease in cholinergic receptors, and is one of the mechanisms underlying these behavioural changes. The effects reported by us are also consistent with other findings showing that developmental exposure to PCBs can cause neurotoxic effects (Seegal, 1996Go). It should be pointed out that in our studies we used low-dose exposure to PCBs.

From our research into the developmental neurotoxic effects of PBDEs (PBDE 47, PBDE 99, PBDE 153, PBDE 209) (Eriksson et al., 2001Go; Eriksson et al., 2002Go; Viberg et al., 2002Go; Viberg et al., 2003aGo; Viberg et al., 2003bGo) we have seen that these agents can cause the same developmental neurotoxic effects as those we have reported for PCBs. Moreover, some of the PBDEs appear to be just as toxic as PCBs. These findings are also of special interest, not only for PBDEs as individual agents for risk assessment but for possible interactive effects between these persistent environmental agents and the current background levels of PCBs.

Recently we also showed at the DIOXIN '03 conference in Boston, Massachusetts, that PCBs and PBDEs can interact during brain development to exacerbate developmental neurotoxic effects (Eriksson et al., 2003Go). The concentrations of PBDEs in human serum have now also reached roughly the same level as for PCBs (Sjödin et al., 2003Go).

When we observe an increase in the levels of PBDEs in our environment—and especially in human mothers' milk—it is incumbent on us to study these new agents to ascertain if they can be as potent in inducing developmental neurotoxic effects as are better known and more extensively studied compounds such as PCBs. We are of the opinion that experiments designed to continuously elicit new scientific information concerning a new class of environmental agents, so conducted that it can be compared with earlier established knowledge of known environmental agents, can be helpful when evaluating the potential risks of new environmental chemicals. This can also be useful when applying the precautionary principle to new chemicals and when the evaluating their possible risks.

REFERENCES

Eriksson, P. (1998). Perinatal Developmental Neurotoxicity of PCBs. Swedish Environmental Protection Agency, Stockholm, Sweden.

Eriksson P, Jakobsson E, Fredriksson A. (2001). Brominated flame retardants: A novel class of developmental neurotoxicants in our environment? Environ. Health Perspect., 109, 903–908.[ISI][Medline]

Eriksson, P., Fischer, C., and Fredriksson, A. (2003). Co-exposure to a polybrominated diphenyl ether (PBDE 99) and an ortho-substituted PCB (PCB 52) enhances developmental neurotoxic effects. Organohalogen Comp., 61, 81–83.

Eriksson P, Viberg H, Jakobsson E, Örn U, Fredriksson A. (2002). A brominated flame retardant, 2,2',4,4',5-pentabromodiphenyl ether: Uptake, retention and induction of neurobehavioural derangement in mice, during a critical phase of neonatal brain development. Toxicol. Sci., 67, 98–103.[Abstract/Free Full Text]

Jakobsson, K., Thuresson, K., Rylander, L., Sjödin, A., Hagmar, L., and Bergman, Å. (2002). Exposure to polybrominated diphenyl ethers and tetrabromobisphenol A among computer technicians. Chemosphere, 46, 709–716.[CrossRef][ISI][Medline]

Seegal, R. (1996). Epidemiological and laboratory evidence of PCB-induced neurotoxicity. Crit. Rev. Toxicol., 26, 709–737.[ISI][Medline]

Sjödin, A., Jones, R. S., Lapeza, C. R., Focant, J-F., Wang, R., Turner, W. E. (2003). Retrospective time study of brominated flame retardants and chlorinated biphenyls in human serum from various regions of the United States from 1985 to 2002. Organohalogen Comp., 61, 1–4.

Viberg H, Fredriksson A, Eriksson P. (2002). Neonatal exposure to the brominated flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether, causes altered susceptibility in the cholinergic transmitter system in the adult mouse. Toxicol. Sci., 67, 104–107.[Abstract/Free Full Text]

Viberg H, Fredriksson A, Eriksson P. (2003a). Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. Toxicol. Appl. Pharmacol., 192, 95–106.[CrossRef][ISI][Medline]

Viberg, H., Fredriksson, A., Jakobsson, E., Örn, Ulrika, and Eriksson, P. (2003b). Neurobehavioural derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development. Toxicol. Sci., 76, 112–120.[Abstract/Free Full Text]





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