Neonatal co-exposure to low doses of an ortho-PCB (PCB 153) and methyl mercury exacerbate defective developmental neurobehavior in mice

Fischer, Celia; Fredriksson, Anders; Eriksson, Per

doi:10.1016/j.tox.2007.11.006

Cited by 48 publications

(22 citation statements)

References 57 publications

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“…Also other in vivo studies using behavioural endpoints: motoric functions [39,60], spatial memory functions [37], open-field behaviour [38] provided no proof of a synergistic or additive PCB/MeHg interaction. The only results suggesting a synergistic type of PCB (PCB 153,126) and MeHg interaction come from the Fisher et al [61] study on mice with the use of the open-field test.…”

Section: Effects Of Combined Exposure To Mehg and Pcb 153mentioning

confidence: 99%

Early developmental effects of separate or combined perinatal exposure to methylmercury (MeHg) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) in the rat

Sitarek¹,

Gralewicz²

2009

International Journal of Occupational Medicine and Environmental Health

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Objectives: Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental pollutants and food contaminants. Both are neurotoxic, especially for the developing nervous system. Material and Methods: Female rats were exposed from day 7 of pregnancy up to day 21 after the delivery to MeHg in drinking water, PCB 153 per os or MeHg+PCB 153. Assessment of the exposure effects in mothers included food and water intake, body weight and reproduction success. Assessment of the progeny comprised determination of body weight, time of pinna detachment, eye opening, incisor eruption, and the negative geotaxis, grip strength and righting reflex. Results: The following effects of the exposures were observed: A) MeHg: 0.5 mg/kg/day -no effect on maternal health status and reproduction. In the progeny: faster incisor eruption and hastened negative geotaxis development. MeHg 2.0 mg/kg/day: In mothers: signs of MeHg toxicity (reduced food intake and body weight, ataxia) during lactation. In the progeny: reduced rate of body weight increase, accelerated incisor eruption but delayed development of the righting reflex. B) PCB 153 exposure: 1.0 mg/kg/day: no effect on maternal health status, reproduction success or morphological and physical development of the progeny; 5.0 mg/kg/day: no effect on maternal health status and reproduction. In the progeny: accelerated growth in females, faster pinna detachment and incisor eruption but delayed development of the grip strength. C) MeHg+PCB153 exposure: none overt effect was noted in mothers or in their progeny. Conclusion: The results confirm the ability of a low level perinatal exposure to MeHg or PCB 153 to affect the early development in the rat. They have not provided, however, an evidence of a synergistic interaction of these contaminants. To the contrary, the results suggest that, at least under the conditions prevailing in the present study, MeHg and PCB 153 interact antagonistically.

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Section: Effects Of Combined Exposure To Mehg and Pcb 153mentioning

confidence: 99%

Early developmental effects of separate or combined perinatal exposure to methylmercury (MeHg) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) in the rat

Sitarek¹,

Gralewicz²

2009

International Journal of Occupational Medicine and Environmental Health

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“…A NOAEL of 0.08 mg/kg b.w. per day was observed by Fischer et al (2008b), in the other studies the lowest tested dose was associated with effects.…”

Section: Neurotoxicity In Young and Adult Animalsmentioning

confidence: 73%

“…The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Remark: The design of this study by Fischer et al (2008b) and of several further studies (as recognizable from the study descriptions) from the Eriksson group is characterized by the following procedure: 8-9 neonate test animals per group have been "randomly selected from at least three litters" to "yield the same statistical effect and power as using litter-based studies". This has been heavily criticized by Hardy and Stedeford (2008) and the results of the study have been mistrusted.…”

Section: Cerebellummentioning

confidence: 99%

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Collate the literature on toxicity data on mercury in experimental animals and humans (Part I – Data on organic mercury)

Hassauer

Kaiser

Schneider

et al. 2012

EFSA Supporting Publications

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It was the scope of this project to collate, compile and summarise the scientific literature on the toxicity of methyl mercury, inorganic mercury and total mercury in humans and experimental animals published since 2002 and not evaluated in former JECFA risk assessments. Epidemiological data on MeHg toxicity confirmed former findings on an association between prenatal exposure and developmental neurotoxicity. Recent findings also support an influence of methyl mercury on the cardiovascular and immune system. Existing epidemiological data reveal several shortcomings limiting their suitability for risk assessment. Developmental neurotoxicity seems to be the most critical effect of MeHg in animals. A LOAEL of 0.01 mg/kg b.w. per day has been reported in young mice for locomotor activity exposed in utero. Rats seem to be less sensitive towards this endpoint: a NOAEL of 0.04 mg/kg b.w. per day has been reported in this species for locomotor activity. Systemic effects other than neurotoxicity have been mostly observed at higher doses than those producing neurotoxicity. No qualified epidemiological data appropriate for the evaluation of the toxicity of inorganic mercury after oral intake have been identified due to several limitations of the studies, e.g. small study group, insufficient control for confounders, inadequate exposure assessment. Toxicological studies in experimental animals widely confirmed former findings with respect to the target organs (neuro-, liver-, kidney-, immune-and reproductive toxicity, oxidative stress). The animal studies indicate that there might be relevant toxicological effects (developmental toxicity, liver toxicity) of inorganic mercury at dose levels similar or below the BMDL 10 value used for the derivation of the existing PTWI. However, due to some limitations of the studies no final conclusions can be drawn from these studies and the findings need further confirmation.

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“…In one study, mice were exposed to MeHg and PCB 153 only once at PND 10. In maturity, in animals exposed to both these neurotoxicants, habituation of the locomotor activity was impaired more severely than in animals exposed to MeHg or PCB alone [37]. In the second study on rats, a combined perinatal exposure to MeHg and Aroclor 1254 resulted in a stronger…”

Section: Effects Of Combined Pcb 153 and Mehg Exposurementioning

confidence: 91%

Neurobehavioural functions in adult progeny of rat mothers exposed to methylmercury or 2,2', 4,4', 5,5'-hexachlorobiphenyl (PCB 153) alone or their combination during gestation and lactation

Gralewicz¹,

Wiaderna²,

Lutz³

et al. 2009

International Journal of Occupational Medicine and Environmental Health

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Objectives: Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants. Both are neurotoxic, especially for the developing brain. The main source of human exposure to MeHg and PCBs is seafood. The aim of the present work was to find out whether and how separate or combined perinatal exposure to these neurotoxicants affects neurobehavioural functions in maturity. Materials and Methods: The study was performed on adult Wistar rats, the progeny of rat mothers exposed to MeHg (0.5 mg/kg/day or 2.0 mg/kg/day), PCB 153 (1.0 mg/kg/day or 5.0 mg/kg/day), or to MeHg 0.5 mg/kg/day + PCB 153 5.0 mg/kg/day, from day 7 of pregnancy to day 21 post partum. The following functions were assessed: spontaneous locomotor activity (open field test), spatial short-term memory (radial maze test), long-term memory (passive avoidance test), sensitivity to pain and vulnerability to stress (hot plate test), efficiency of the sensorimotor gating (startle response test), and sensorimotor coordination (the rotarod test). Results:The results obtained in the MeHg part of the study showed a reduced locomotor activity in the female progeny of both exposed groups, an impaired passive avoidance in the male progeny of the high and low exposure group and a faster recovery from the effects of the stressful experience (hot plate test) in the male progeny of the high dose group. Results obtained in the PCB part showed an increased locomotor activity in the female progeny of both exposure groups and impairment in rotarod performance in males of the high dose group. Neurobehavioural alterations were not found in either the females or males exposed jointly to MeHg and PCB 153. Conclusions: The results suggest that in condition of the combined exposure, MeHg may protect against the effects of PCB 153 and vice versa.

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Neonatal co-exposure to low doses of an ortho-PCB (PCB 153) and methyl mercury exacerbate defective developmental neurobehavior in mice

Cited by 48 publications

References 57 publications

Early developmental effects of separate or combined perinatal exposure to methylmercury (MeHg) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) in the rat

Early developmental effects of separate or combined perinatal exposure to methylmercury (MeHg) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) in the rat

Collate the literature on toxicity data on mercury in experimental animals and humans (Part I – Data on organic mercury)

Neurobehavioural functions in adult progeny of rat mothers exposed to methylmercury or 2,2', 4,4', 5,5'-hexachlorobiphenyl (PCB 153) alone or their combination during gestation and lactation

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