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Study director / genotoxicologist
Work description :
Study director for in vitro genotoxicity assays and other in vitro studies in line with GLP
Establishment and development of new in vitro methods
Leading of research projects involving design, implementation, reporting and publication of the project

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The environment not only alters our genes, but also our gene expression. Alteration of the genes are well documented and can be determined with several validated in vitro and in vivo methods, however aleterations of gene expression is a new and complex field, termed epigenetics.

Epigenetics is the study of heritable changes in gene expression or phenotype occurring
without changes in DNA sequence.

This review focuses on the evidence that the prenatal/fetal period is highly susceptible to
epigenomic dysregulation with implications for health, both lifelong and transgenerationally. There are examples of developmental exposure to various environmental pollutants shown to induce epigenetic changes and neurodevelopmental deficits and diseases.

Prenatal Environmental Exposures, Epigenetics, and Disease

Frederica Perera and Julie Herbstman

Copyright © 2011 Published by Elsevier Inc.

Zadnjič posodobljeno (Sobota, 22 Januar 2011 08:47)


The toxicants that accumulate in vast areas have potentially severe adverse effects locally on the people directly, as well as through the food chain via animal and plant life. When the toxicants get into the ground water as well as the air, the adverse effects may spread around the world.

Zadnjič posodobljeno (Petek, 21 Januar 2011 05:20)


Sedež Slovenskega toksikološkega društva (STD)

je na Veterinarski fakulteti,

Gerbičeva 60

1115 Ljubljana

Kontaktna oseba na VF je prof. dr. Silvestra Kobal

Zadnjič posodobljeno (Petek, 14 Januar 2011 06:46)


Written by Ester Lovšin Barle

On the April 28, 2009 it was announced on the US Labor Department's Occupational safety and health association (OSHA) national news release in the USA, that the Secretary of Labor Hilda L. Solis announced convening of rulemaking panel on worker exposure to food flavorings containing diacetyl. A month earlier, she withdrew an Advance Notice of Proposed Rulemaking to facilitate timely development of a standard to protect workers from bronchiolitis obliterans, a serious and potentially fatal lung disease associated with exposure to diacetyl. "I am alarmed that workers exposed to food flavorings containing diacetyl may continue to be at risk of developing a potentially fatal lung disease. Exposure to this harmful chemical already has been linked to the deaths of at least three workers," said Solis.


Diacetyl (also called butanedione or 2,3-butanedione, molecular formula C4H6O2) is a natural byproduct of fermentation and is also synthesized by chemical manufacturers. Diacetyl gives a distinctive buttery flavor and aroma. Food flavorings containing diacetyl are used in microwave popcorn and other snack foods, pet foods, candies, baked goods, and other food products. Diacetyl, at low level, gives beer or wine a slippery feel. At higher levels one can taste a butterscotch flavor. Diacetyl has a flashpoint of 47 degrees Fahrenheit and is, therefore, a flammable liquid.

Animal data

In acute exposure study in rats via inhalation, butter flavoring vapors containing 285-371 ppm diacetyl caused necrotizing bronchitis, which was most consistently present in the mainstem bronchus. Alveoli were unaffected. Butter flavoring vapors containing 203-371 ppm diacetyl caused necrosuppurative rhinitis (inflammation of the nose epithelia marked by death of the epithelial cells, creating pus). Therefore, concentrations of butter flavoring vapors that can occur during the manufacture of foods are associated with epithelial injury in the nasal passages and pulmonary airways of rats. This study was performed in 2002. Subchronic and chronic, as well as reproductive toxicity studies were performed with oral administration, showing decreases in weight gain, increases in water consumption, anemia and increased leukocyte count, increase weight of several organs, as well as necrotic stomach lesions, which is an irreversible effect. This study was performed in 1969. Reproductive studies have shown no effect on reproduction/fertility in animals. Diacetyl was weakly mutagenic in Ames study at 6 umoles/ plate and caused mixed results in other genotoxicity tests. In 1973 a carcinogenicity study was performed and found no tumors in 24 weeks of application via intra peritoneal route. This study is of questionable relevance due to its short duration and the route of administration which does not resemble an actual route of entry for the workers or consumers.

As seen from the animal data, the studies which were performed with a relevant route of exposure for occupational health have indicated a severe effect on the respiratory tract.

Human data

The National Institute for Occupational Safety and Health (NIOSH) reported that medical tests of employees at microwave popcorn plants showed fixed airways obstruction, some cases consistent with bronchiolitis obliterans, and other respiratory illnesses such as occupational asthma. NIOSH concluded that the lung diseases identified in these microwave popcorn plant employees were likely due to exposure to butter flavoring chemicals (reports from 2003 up to 2006). NIOSH also described cases of fixed airways obstruction, including three cases consistent with bronchiolitis obliterans, among employees producing butter and vanilla flavorings containing diacetyl at a flavorings manufacturing facility.

Bronchiolitis obliterans is a disease of the lungs. The bronchioles are plugged with granulation tissue. It is a rare and life-threatening disease. A patient with bronchiolitis obliterans may experience shortness of breath and have a dry cough, he/she may also be wheezing a lot. His/her lung capacity will be at about 16% to 21% lung usage, compared to a normal capacity of 80%. There is no cure for this disease, apart from a lung transplant. Treatment is extremely limited.

Exposure protection

In January 2005, NIOSH recommended that employers take measures to limit their "occupational respiratory exposures to food flavorings and flavoring ingredients in workplaces where flavorings are made or used."

NIOSH has determined that effective controls for employers in microwave popcorn packaging plants using include isolation of mixing processes (i.e. enclosures) and use of local and general exhaust ventilation to reduce inhalation exposure. Based on the NIOSH investigations of microwave popcorn plants, a NIOSH-certified air-purifying respirator equipped with organic vapor cartridges in combination with particulate filters would provide the minimum level of protection. Supplied air respirators can also be used in these facilities. Powered air-purifying respirators (PAPRs) (with organic vapor cartridges and particulate filters) are acceptable alternatives and may be easier for employees to wear in hot mixing rooms.

Gloves and aprons made from butyl rubber are effective in reducing skin contact with ketones to prevent skin irritation. Chemical-resistant gloves or sleeves, or other appropriate protection for exposed skin must be used when handling liquid, paste, or powdered flavoring ingredients that could cause dermal injury. Employees must use chemical goggles or other appropriate eye protection when working with diacetyl.

Lessons learned

1. Well performed toxicological experiments with applicable route of exposure on animals have the ability to determine the health hazards that may be relevant for humans. However there are only few cases when inhalation is used as an administration route. In pharmaceutical industry these cases are limited to the medicinal drugs intended for inhalation.

2. Flavoring agent might be considered a non-toxic substance due to its wide use and no determined limits. However toxicity of chemicals (active pharmaceutical ingredients, excipients, additives, vitamins etc.) can not be determined based on the substance’s popular classification.

3. Things change. With additional animal studies and frequent human exposure, new data is available and hazard identification may be shown as more, or less severe then previously anticipated.

More on diacetyl, the toxic butter flavor and the workplace environment also at CDC NIOSH

Zadnjič posodobljeno (Sreda, 12 Januar 2011 14:19)