Yale scientists show how bisphenol A induces epigenetic changes in pregnant mice that cause hormonal imbalance in the later life of female progeny

Here’s more evidence that “safe” plastics are not as safe as once presumed: New research published online in The FASEB Journal suggests that exposure to Bisphenol A (BPA) during pregnancy leads to epigenetic changes that may cause permanent reproduction problems for female offspring. BPA, a common component of plastics used to contain food, is a type of estrogen that is ubiquitous in the environment.

“Exposure to BPA may be harmful during pregnancy; this exposure may permanently affect the fetus,” said Hugh S. Taylor, Ph.D., co-author of the study from Yale University School of Medicine in New Haven, Connecticut. “We need to better identify the effects of environmental contaminants on not just crude measures such as birth defects, but also their effect in causing more subtle developmental errors.”

Taylor and colleagues made this discovery by exposing fetal mice to BPA during pregnancy and examining gene expression and DNA in the uteruses of female fetuses. Results showed that BPA exposure permanently affected the uterus by decreasing regulation of gene expression. These epigenetic changes caused the mice to over-respond to estrogen throughout adulthood, long after the BPA exposure. This suggests that early exposure to BPA genetically “programmed” the uterus to be hyper-responsive to estrogen. Extreme estrogen sensitivity can lead to fertility problems, advanced puberty, altered mammary development and reproductive function, as well as a variety of hormone-related cancers. BPA has been widely used in plastics and other materials. Examples include use in water bottles, baby bottles, epoxy resins used to coat food cans, and dental sealants.

“The BPA baby bottle scare may be only the tip of the iceberg.” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Remember how diethylstilbestrol (DES) caused birth defects and cancers in young women whose mothers were given such hormones during pregnancy. We’d better watch out for BPA, which seems to carry similar epigenetic risks across the generations. ”

Author: FASEB* – Federation of American Societies for Experimental Biology, Why BPA leached from ’safe’ plastics may damage health of female offspring, 25-Feb-2010.

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* FASEB comprises 23 societies with more than 90,000 members, making it the largest coalition of biomedical research associations in the United States

Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction, infertility, cryptorchidism, hypospadias and testicular cancer.

Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time periods past 50 years. Except for testicular cancer this evidence is circumstantial and needs cautious interpretation. However, the male germ line is one of the most sensitive tissues to the damaging effects of ionizing radiation, radiant heat and a number of known toxicants.

So far occupational hazards are the best documented risk factors for impaired male reproductive function and include physical exposures (radiant heat, ionizing radiation, high frequency electromagnetic radiation), chemical exposures (some solvents as carbon disulfide and ethylene glycol ethers, some pesticides as dibromochloropropane, ethylendibromide and DDT/DDE, some heavy metals as inorganic lead and mercury) and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures, but millions of workers in less affluent countries are at risk from reproductive toxicants. New data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world.

For other noxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds as phthalates, bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones.

Finally, there are data indicating a particular vulnerability of the fetal testis to toxicants – for instance maternal tobacco smoking. Time has come where male reproductive toxicity should be addressed form entirely new angles including exposures very early in life.

Literatur:
Bonde JP., Male reproductive organs are at risk from environmental hazards, Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, Copenhagen, Denmark, Asian J Androl. 2009 Dec 7.

Press release of the German Professional Association of Environmental Medicine (Deutscher Berufsverband der Umweltmediziner – DBU)

from 26. October 2009

Swine flu vaccine is unsuitable for patients with environmental diseases and other chronic multi-system illnesses.  Pandemrix® poses substantial health risk with respect to mass immunization programs due to the lack of proof of safety.  Because of the producer’s release from liability by the German Federal Government (BRD), the risk of adverse reactions and/or permanent damage due to the vaccine rests with the patient.

The German Professional Association of Environmental Medicine (DBU) has, in spite of press releases from the BRD, the Paul-Ehrlich-Institute, as well as the vaccine producer’s assurances of safety, serious concerns relating to Pandemrix® (GlaxoSmithKline), the only vaccine which has been approved for mass vaccination by the BRD.

The DBU discusses at this point neither the medical use of immunization in general nor the necessity of such measures in the, up until now, mild course of the swine flu pandemic.

Our criticism is directed only against the pandemic vaccine Pandemrix®.

• There exists considerable doubt as to the effectiveness of the vaccine: during the licensing phase, the vaccine tested had a 40% higher portion of virus antigen (5. 25µg) than the vaccine (3.75µg) now being delivered. An unequivocal consensus has not been reached as to whether the vaccination should be given once or twice a season !!!

• There exists considerable doubt concerning the safety of the adjuvanted active amplifier since it is being used for the first time. The vaccine contains 27.4mg AS03, an emulsion of polysorbate, squalene and tocopherol. Sufficient studies are lacking, because in the test phase, only the development of antibody titers was determined as a surrogate criterion, and not any potential adverse reactions.

• The producer as well as government agencies have concealed the fact that squalene, if used subcutaneously or intramuscularly is an inflammatory immune activation immunogen, unlike when ingested. (Squalene is, among other things, for example, naturally contained in olive oil.)

• Autoimmune diseases can be provoked by squalene; already existing ones can be activated. Squalene has been connected with the emergence of Guillan-Barré Syndrome (GBS) and is now considered a trigger for Gulf War Syndrome (GWS). In animal studies squalene brought on rheumatoid arthritis.

• Squalene from food sources is mainly incorporated into membranes in the body. The production of squaline antibodies resulting from an immunization sets off chronic inflammation of the membranes, which explains diseases such as Gulf War Syndrome and also degenerative neurological diseases such as Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Chronic Inflammatory Demyelinating Polyneuropathy and Guillan-Barré Syndrome.

• The delivery of vaccine in multiple dose ampules is obsolete. In single dose ampules the mercury used for preservation, as in thimerosal – which is included in Pandemrix – would be unnecessary.  Also, mercury has been proven to set off autoimmune diseases.

• Since the vaccine has not been tested on either young children or pregnant women (Ethics Commission objection), the call to give preference in the first phase of vaccination to precisely this particularly endangered segment of the population represents an improper and totally unjustifiable field test.

• The vaccine poses a higher risk than the swine flu itself for patients with environmental illness and for patients with compromised immune systems (e.g. AIDS).

• The vaccine producer GlaxoSmithKline (GSK), according to the contract with the BRD, is largely exempt from liability. In case of damage from the vaccination, the affected vaccinee would have to sue the government and therefore the country of Germany, usually a futile exercise.

• To avoid the trap of liability, the doctor giving the vaccination must meticulously inform the patient of all risks concerning the vaccination and the vaccine. It is recommended to give this information in the presence of an assistant and to have it be confirmed by the patient’s signature. The explanation should also include the liability features. Also the indication that other, lower risk vaccines are available in Europe and that due to a faulty decision by the German government, they are currently not available to the German population. This information should definitely be included in the explanation.

For general and environmental health considerations the DBU urgently advises against carrying out a vaccination with Pandemrix® !

Dr.med. Hans-Peter Donate

for the board of the German Professional Association of Environmental Medicine (DBU)

Translation: CSN – Chemical Sensitivity Network

This article aims to describe essential conditions and starting-points for the monetary evaluation of environmentally attributable diseases. Furthermore, a cost calculation within a scenario analysis is conducted for Germany. 

To calculate the costs of environmental health effects we chose a disease-specific perspective. The national statistics of the Federal Statistical Office and the World Health Report burden of disease estimates were used to identify the most important disease categories for Germany. Based on an extensive literature research in computerized databases and the publications of national and international institutions, available costs of illness studies for Germany as well as environmental attributable fractions (EAFs) were identified. Based on these data environmental health costs were calculated with a top-down approach. 

Direct and indirect environmental costs of illness add up to 15-62 billion euro (2006) per year depending on the specific scenario. From our results a tentative scheme is deduced of how the monetary environmental burden of specific diseases is composed and how it can be assigned to major environmental exposures and economic sectors which can be used in setting intervention priorities and evaluating intervention efficiency. 

Within this article, we were able to calculate environmental health costs for Germany based on available, easy to access data and deduce implications for environmental policy decision-making. However, there are restrictions in data quality, as the aetiology of some diseases with respect to environmental impacts is not very well documented and data has not been collected particularly for Germany. 

Reference:   Haucke F, Brückner U., First approaches to the monetary impact of environmental health disturbances in Germany, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Institute of Health Economics and Health Care Management, Germany, Health Policy. 2009 Sep 8.

Epidemiologic studies suggested a possible link between prenatal exposure to organophosphate insecticides (OP) and long-term mental delay and some behavioral troubles. Experimental studies in rats and mice have confirmed that a relatively short exposure to low doses of OP such as Chlorpyrifos (CPF) during specific perinatal periods decreased anxiety-like behaviors.  

In the present study, we report that chronic perinatal exposure (GD15-PND14) to low doses of CPF lead to an increase (and not a decrease) in anxiety-like behaviors of female mouse offspring. Pregnant or lactating female mice were exposed to CPF (0.2; 1; or 5 mg/kg.day) by oral treatment during 18 consecutive days.  

Following a recovery period of several weeks, the anxiety of adult female offspring was determined using neurobehavioral tests (elevated plus-maze and light/dark box tests).  

Our results showed that CPF-exposed female offspring were more anxious than controls. In addition, the magnitude of anxiety profile alterations depended on the level of exposure to CPF during gestation and lactation with a maximal effect observed at the 1 mg/kg.day dose.  

Our results confirm that OP exposure during the perinatal period can induce long-term alterations in mouse anxiety-like behaviors and suggest that the routes of administration and the duration of OP exposure during brain development may be factors to consider when studying the development of anxiety. 

Reference:   Braquenier JB, Quertemont E, Tirelli E, Plumier JC., Anxiety in adult female mice following perinatal exposure to Chlorpyrifos, Neurotoxicol Teratol. 2009 Aug 27.