Discovery of mutagenesis

In the 1920s, Hermann Muller discovered that x-rays caused mutations in fruit flies. He went on to use x-rays to create Drosophila mutants that he used in his studies of genetics. He also discovered that x-rays not only mutate genes in fruit flies but also have effects on the genetic makeup of humans.[1] The first mutagens to be identified were carcinogens, or cancer-causing substances. Earlyphysicians detected tumors in patients more than 2,000 years before the discovery of chromosomes and DNA. In 500 B.C., the Greek Hippocrates named crab-shaped tumors cancer, meaning crab.

In England in 1775, Dr. Percivall Pott wrote a paper on the high incidence of scrotal cancer in chimney sweeps who were typically boys small enough to fit inside chimneys and clean out the soot. Pott suggested that chimney soot contained carcinogens that could cause the growth of the warts seen in scrotal cancer. Over 150 years later, chimney soot was found to contain hydrocarbons capable of mutating DNA.

In France in the 1890s, Bordeaux wine workers showed an unusually high incidence of skin cancer on the back of the neck. These workers spend their days bending over in the fields picking grapes, exposing the back of their necks to the sun. The ultraviolet (UV) radiation in natural sunlight was later identified as a mutagen.

Nature of mutagens

Mutagens are usually chemical compounds or ionizing radiation. Mutagens can be divided into different categories according to their effect on DNA replication:

• Some mutagens act as base analogs and get inserted into the DNA strand during replication in place of nucleotides.
• Some react with DNA and cause structural changes that lead to miscopying of the template strand when the DNA is replicated.
• Some work indirectly by causing the cells to synthesize chemicals that have the direct mutagenic effect.

The Ames test is one method to determine how mutagenic an agent is. 

Carcinogens 

A carcinogen is a substance that causes cancer (or is believed to cause cancer).

A carcinogenic material is one that is known to cause cancer. The process of forming cancer cells from normal cells or carcinomas is called carcinogenesis.

A known human carcinogen means there is sufficient evidence of a cause and effect relationship between exposure to the material and cancer in humans. Such determination requires evidence from epidemiology, clinical, or tissue/cell studies involving humans who were exposed to the substance in question. Obviously, it is unethical to deliberately test potential carcinogens on humans, so "proving" something (in the rigorous scientific sense) to be a carcinogen in humans is a difficult, demanding and lengthy task!

Substances that are reasonably anticipated to be human carcinogens meet any of the following descriptions:

• There is limited evidence of carcinogenicity from studies in humans. A cause and effect interpretation is credible, but that alternative explanations such as chance, bias, other variables etc. can not be ruled out. Again, science can never prove a hypothesis, only disprove one. Scientific "facts" are established only when a preponderence of the evidence supports a hypothesis and there is 1) no evidence to disprove it and 2) no equally viable alternative hypotheses.
• There is sufficient evidence of carcinogenicity from studies in experimental animals, which indicates there is an increased incidence of malignant and/or a combination of malignant and benign tumors (1) in multiple species or at multiple tissue sites, or (2) by multiple routes of exposure, or (3) to an unusual degree with regard to incidence, site, or type of tumor, or age at onset.
• There is less than sufficient evidence of carcinogenicity in humans or laboratory animals; however, the substance is structurally related to other materials that are either human carcinogens or reasonably anticipated to be human carcinogens
• There is convincing relevant information that the material acts through mechanisms that are likely to cause cancer in humans.

A wide variety of information is required to assess carcinogenicity and risks to humans. For example, a substance may cause cancer in laboratory animals, but the mechanism by which this occurs may not occur in humans.

Cancer is a disorder in which the mechanisms which control proliferation of cells no longer function adequately. Because of the implications of this 'biomagnifier' effect leading to irreversible life-threatening changes, it is an emotive subject and chemical carcinogenicity has commonly been perceived to be different from other forms of chemical toxicity.

The International Agency for Research on Cancer (IARC) is part of the World Health Organization. IARC's mission is to coordinate and conduct research on the causes of human cancer, the mechanisms of carcinogenesis, and to develop scientific strategies for cancer control. The Agency is involved in both epidemiological and laboratory research and disseminates scientific information through publications, meetings, courses, and fellowships.

Сarcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage thegenome or to the disruption of cellular metabolic processes. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit. Common examples of carcinogens are inhaled asbestos, certaindioxins, and tobacco smoke. Cancer is a disease in which damaged cells do not undergo programmed cell death. Carcinogens may increase the risk of cancer by altering cellular metabolism or damaging DNA directly in cells, which interferes with biological processes, and induces the uncontrolled, malignant division, ultimately leading to the formation of tumors. Usually DNA damage, if too severe to repair, leads to programmed cell death, but if the programmed cell death pathway is damaged, then the cell cannot prevent itself from becoming a cancer cell.

There are many natural carcinogens. Aflatoxin B1, which is produced by the fungus Aspergillus flavus growing on stored grains, nuts and peanut butter, is an example of a potent, naturally-occurring microbial carcinogen. Certain viruses such as Hepatitis B and human papilloma viruses have been found to cause cancer in humans. The first one shown to cause cancer in animals is Rous sarcoma virus, discovered in 1910 by Peyton Rous.

Dioxins and dioxin-like compounds, benzene, kepone, EDB, and asbestos have all been classified as carcinogenic. As far back as the 1930s, industrialsmoke and tobacco smoke were identified as sources of dozens of carcinogens, including benzo[a]pyrene, tobacco-specific nitrosamines such asnitrosonornicotine, and reactive aldehydes such as formaldehyde—which is also a hazard in embalming and making plastics. Vinyl chloride, from which PVCis manufactured, is a carcinogen and thus a hazard in PVC production.

Co-carcinogens are chemicals that do not necessarily cause cancer on their own, but promote the activity of other carcinogens in causing cancer.

After the carcinogen enters the body, the body makes an attempt to eliminate it through a process called biotransformation. The purpose of these reactions is to make the carcinogen more water-soluble so that it can be removed from the body. But these reactions can also convert a less toxic carcinogen into a more toxic carcinogen.

DNA is nucleophilic, therefore soluble carbon electrophiles are carcinogenic, because DNA attacks them. For example, some alkenes are toxicated by human enzymes to produce an electrophilicepoxide. DNA attacks the epoxide, and is bound permanently to it. This is the mechanism behind the carcinogenity of benzo[a]pyrene in tobacco smoke, other aromatics, aflatoxin and mustard gas.

Teratogens (and embryotoxins or fetotoxins) 

A teratogen is an agent that can cause malformations of an embryo or fetus. This can be a chemical substance, a virus or ionizing radiation.

This is closely related to a embryotoxin, an agent that causes poisoning effects on a developing fetus.

Both embryotoxins and teratogens are reproductive toxins, substances which cause damage to one's reproductive and/or endocrine system and/or a developing fetus.

Pregnant women should avoid all contact with teratogens, particularly during the first three months of pregnancy, as this can result in damage to the developing child. For example, alcohol is a teratogen and drinking during pregnancy can lead to a child born with fetal alcohol syndrome.

Many drugs can also have an adverse effect on developing fetuses, the most infamous example being thalidomide. This drug was used to control morning sickness, but was withdrawn from the market after it was discovered to cause limb and other developmental deformities.

There are few examples of transplacental carcinogens, substances which can cause fetuses exposed during pregnancy to eventually develop cancer. The best-known example is DES, diethylstilbestrol, a compound formerly used to prevent miscarriages before its trans-generational carcinogenic activity was known.

Always minimize the use and release of teratogens (or believed teratogens) in the workplace. Women who are of child-bearing age should pay particular attention to teratogenic materials because they could be pregnant without knowing it and expose their fetus. Teratogens typically cause their most severe damage during the first 3 months of pregnancy when many pregnancies are not yet known. Many teratogens cause effects at very low exposure levels.

Embryotoxins are substances that act during pregnancy to cause adverse effects on the developing fetus. These effects may include embryolethality (death of the fertilized egg, the embryo, or the fetus), malformations (teratogenic effects), retarded growth, and postnatal function deficits. A few substances have been demonstrated to be embryotoxic in humans. 

Stockholm Convention on Persistent Organic Pollutants 

Persistent organic pollutants are a category of chemicals including some that have become household names for their danger to human health. The category includes DDT, polychlorinated biphenyls (PCBs), and dioxins.

Completed in 2001, this treaty aims to protect human health and the environment from chemicals that share four intrinsic characteristics:

• they are toxic;
• they have the potential to accumulate in unhealthy quantities in humans and animals;
• they are stable and thus resistant to natural breakdown; and
• they can be transported over long distances through the atmosphere and oceans.

POPs are capable of affecting human health and the environment far away from the regions where they are used and released. While none of the twelve chemicals covered by the Stockholm Convention are now used or manufactured in the United States, there are still some uses in other parts of the world, particularly in developing countries. As a result, they can still have a negative impact on the health of U.S. citizens. These chemicals have been linked to cancer, damage to the nervous system, reproductive disorders, and/or weakening of the immune system. Some POPs, such as DDT, are known to have negative effects on the wildlife species themselves. Because POPs are capable of long-range transport, no one country acting alone can address their human health and environmental effects. A global agreement was needed to control the use and release of these substances.

The Stockholm Convention deals with intentionally produced POPs, such as DDT or PCBs; unintentionally produced POPs, such as dioxins and furans; and POPs wastes. For intentionally produced POPs, the Convention prohibits or restricts their production and use, subject to certain exemptions such as the continued use of DDT for malaria and other disease vector control. The Convention also prohibits or restricts trade in such substances. For unintentionally produced POPs, the Convention requires countries to develop national action plans to address releases and to apply "Best Available Techniques" to control them. Parties must also take appropriate measures to ensure that POPs wastes are managed in an environmentally-sound manner.

It can be difficult for developing countries to manage POPs; therefore the Convention includes a flexible system of financial and technical assistance through which these countries can receive help to meet their obligations. The United States has spent over $20 million assisting several developing countries addressing this issue.

Finally, the Stockholm Convention creates a science-based procedure to govern the addition of new chemicals beyond the current twelve. The process will allow a subcommittee of scientific experts to review and recommend to the Parties to the Convention whether the chemical is likely, as a result of its long-range environmental transport, to lead to significant adverse human health or environmental effects, such that global action is warranted." The Convention entered into force on 17 May 2004 and has so far been ratified by 144 Parties. The United States helped negotiate this treaty and signed it in 2001, but it has not yet become a Party to the Convention.

History

In 1995, the Governing Council of the United Nations Environment Programme (UNEP) called for global action to be taken on POPs, which it defined as "chemical substances that persist in the environment, bio-accumulate through the food web, and pose a risk of causing adverse effects to human health and the environment".

Following this, the Intergovernmental Forum on Chemical Safety (IFCS) and the International Programme on Chemical Safety (IPCS) prepared an assessment of the 12 worst offenders, known as the dirty dozen.

The negotiations for the Convention were completed on 23 May 2001 in Stockholm. The convention entered into force on 17 May 2004 with ratification by an initial 128 parties and 151 signatories. Co-signatories agree to outlaw nine of the dirty dozen chemicals, limit the use of DDT to malaria control, and curtail inadvertent production of dioxins and furans.

Parties to the convention have agreed to a process by which persistent toxic compounds can be reviewed and added to the convention, if they meet certain criteria for persistence and transboundary threat. The first set of new chemicals to be added to the Convention were agreed at a conference in Geneva on 8 May 2009.

As of April, 2011, there are 173 parties to the Convention.

Problems associated with pesticides

Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.  A pesticide may be a chemical substance, biological agent (such as a virus or bacterium), antimicrobial, disinfectant or device used against any pest. Pests include insects, plant pathogens, weeds, molluscs, birds, mammals, fish, nematodes (roundworms), and microbes that destroy property, spread disease or are a vector for disease or cause a nuisance. Although there are benefits to the use of pesticides, there are also drawbacks, such as potential toxicity to humans and other animals. According to the Stockholm Convention on Persistent Organic Pollutants, 9 of the 12 most dangerous and persistent organic chemicals are pesticides

About 60 years ago, when DDT and other organochlorine pesticides became popular in agriculture, they  were considered a safe and effective way to get rid of pests. But over the years, more and more problems associated with the use of pesticides have shown up. Major problems include: 

• harmful side effects on non-target organisms (people, animals, soil, water, etc.)
• resurgence of pest populations (because natural control is disrupted)
• the development of resistance
• the cost

 

Toxicity for non-target organisms

The use of pesticides (both synthetic and organic) always involves certain risks because of their poisonous character. Who is at risk?

Farmers and their family members run the highest risks. They can easily come in contact with the pesticides, for example when mixing the chemicals or when applying them to the crop.  

The pesticides that were sprayed on the crop can leave behind residues that will be eaten by the consumers.

Pesticides will not only reach the target organisms but will also kill other organisms (e.g. beneficial insects, birds, earthworms, fish) in or around the crop fields, causing loss of biodiversity, deaths of wild life, and death of farm animals. Soil, air and water bodies can easily be contaminated with these poisonous chemicals. The unavoidable destruction of beneficial insects and spiders interferes with natural pest control.

The mentioned risks are most obvious when pesticides cause acute toxicity to man, domestic animals and non-target organisms such as fish, bees, birds and soil organisms. The more subtle long-term chronic effects (disruption of endocrine system, cancer, sterility and mutagenic effects) often go unnoticed and are not yet fully understood.

Also in the environment, some pesticides have not only acute effects but also long-term effects. Especially the "persistent organic pollutants" (POPs) will continue to poison non-target organisms in the environment and will also appear as crop residues long after their use has ceased.

No pesticide, synthetic or organic, is considered "safe". However, some are less dangerous to use than others, depending on their effect on living organisms. Before using a pesticide, it is essential to be well informed about the various effects it may have. Farmers have to know how to reduce the risks.

Resurgence