PCBs (Polychlorinated biphenyl)

The possible positions of chlorine atoms on the benzene rings are denoted by numbers assigned to the carbon atoms.
Polychlorinated biphenyls (PCBs) are a class of organic compounds
with 1 to 10 chlorine atoms attached to biphenyl, which is a molecule composed
of two benzene rings.
PCBs were widely used for many applications,
especially as dielectric fluids in transformers, capacitors, and coolants. Due to PCB's toxicity and classification as a persistent organic pollutant, PCB production was banned by the United States Congress in 1979 and by the Stockholm Convention on Persistent Organic Pollutants in 2001.
Concerns about the toxicity of PCBs are largely based on compounds within this group that share a structural similarity and toxic mode of action with dioxin.
Toxic effects such as endocrine disruption and neurotoxicity are also associated with other compounds within the group.

Physical and chemical properties
PCB congeners are odorless, tasteless, clear to pale-yellow, viscous liquids (highly chlorinated mixtures are more viscous and deeper yellow). They are formed by electrophilic chlorination of biphenyl with chlorine gas.

PCBs have low water solubilities — 0.0027-0.42 ng/L for Aroclors, and low vapor pressures at room temperature, but they have high solubilities in most organic solvents, oils, and fats. They have high dielectric constants, very high thermal conductivity, high flash points (from 170 to 380 °C) and are chemically fairly inert, being extremely resistant to oxidation, reduction, addition, elimination, and electrophilic substitution.

The density varies from 1.182 to 1.566 kg/L. Other physical and chemical properties vary widely across the class. As the degree of chlorination increases, melting point and lipophilicity increase, and vapour pressure and water solubility decrease.
PCBs readily penetrate skin, PVC (polyvinyl chloride), and latex (natural rubber). PCB-resistant materials include Viton, polyethylene, polyvinyl acetate (PVA), polytetrafluoroethylene (PTFE), butyl rubber, nitrile rubber, and Neoprene.
In terms of structural relationship to toxicity, PCBs fall into 2 distinct categories, referred to as coplanar or non-ortho-substituted arene substitution patterns and noncoplanar or ortho-substituted congeners. The coplanar group members have a fairly rigid structure, with the 2 phenyl rings in the same plane.
This gives the molecule a structure similar to polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans, and allows it to act in the same way as these molecules as an agonist of the aryl hydrocarbon receptor (AhR) in organisms. These type of PCBs are considered as contributors to overall dioxin toxicity, and the term dioxin is often used interchangeably when the environmental and toxic impact of these compounds is considered. Noncoplanar PCBs, with chlorine atoms at the ortho positions, have not been found to activate the AhR, and are not considered part of the dioxin group; however, studies have indicated some neurotoxic and immunotoxic effects, but at levels much higher than normally associated with dioxins, and thus of much less concern to regulatory bodies.

PCBs are very stable compounds and do not decompose readily. Their destruction by chemical, thermal, and biochemical processes is extremely difficult, and presents the risk of generating extremely toxic dibenzodioxins and dibenzofurans through partial oxidation. Intentional degradation as a treatment of unwanted PCBs generally requires high heat or catalysis (see Methods of destruction below).
Written by Carole Pointet Student in Health Safety & Environement

References:

THE MISSING PEREGRINE: CHLORINATED HYDROCARBONS

Decline of birds of prey, populations seriously depleted:  

• Peregrine Falcon in UK with all known territories deserted by 1992 
• Europe: Golden Eagle and Sparrow Hawk 
• USA: Bald Eagle, Osprey, Cooper’s Hawk 

Decline due to bird’s eggs fragility, resulting in many not being viable: Ratcliffe in 1967, demonstrated that shell egg thickness had declined sharply since the 1940s by observing egg collections, but tracking the source of the problem proved difficult. 

It was noticed that the level of decline in Sparrow Hawk was relative to the intensity of the agriculture and the use pesticide, but the evidence was only circumstancial. Pesticides toxic impact had been previously denounced in Rachel Carson’s book, “Silent Spring” in 1963. 

Three main groups of chlorinated hydrocarbons were thought responsible of the decline: 

• Polychlorinated Byphenols (PCBs): manufactured from the 1920s by Monsanto for electrical insulation, heat transfer fluids, hydraulic systems or in plastics. When plastics are burnt PCBs are released in the atmosphere. 

• Organochlorine pesticides (OCs): DDT (Dichloro-diphenyl-trichloroethane) from 1945 which was extremely performant against Malaria, now banned in most countries but still used in India and parts of Africa. 

Other OCs are lindane and chlordane which were pesticides to control pests from cabbages (brassicas), top fruits and cereals. 

• Cyclodiene pesticides (drins) from 1950 to control soil pests (cabbage root fly in brassicas, wireworms in potatoes). Example: Dieldrin, Aldrin, Heptachlor. 

At first Organochlorine Pesticides (OCs) thought not responsible as were shown to be non-toxic to vertebrates: tests on humans showed no signs of toxicity, however they were administered a very small dose during trial (0.5 mg kg⁻¹) when toxic effects in humans are noted at 10 mg kg¯¹. Based on these tests the link between bird decline and OCs wasn’t established at first. 

It was then established that three properties of OCs were a significant risk to birds: 

1. The breakdown products of OCs are very persistent 

DDT (Dichloro-diphenyl-trichloroethane) metabolic pathway: breaks down to DDD (Dichloro-diphenyl-dichloroethane) then finally to DDE (Dichloro-diphenyl-ethane). Thus finding the metabolite DDE proves DDT is involved.

2. Organochlorine pesticides are hydrophobic, so insoluble in water but highly soluble in lipids where they bioaccumulate. This can be shown with a liver biopsy. 

3. Organochlorine pesticides concentrations are magnified up the food chain: biomagnification thus higher animals have much higher concentrations of DDE. 

However, even though OCs were linked to eggshell thinning of birds of prey, the cause was not yet determined. A study involving Ring Doves was conducted where 12 pairs of doves were fed 40ppm of DDE for 126 days, and the results measured against a set of controls again of 12 pairs of doves. It was observed that the tested pairs nested fewer times with longer periods in-between. They also laid less eggs which had thinner eggshells and a significantly higher mortality rate of the young.  

The experiment established that the organochlorine pesticides affected the reproduction, and the cause was found when it was discovered in another unrelated experiment that chlordane, an OC, could induce the activation of the cytochrome P450 enzyme. Indeed, P450 can metabolise the natural chemical oestrogen, a hormone that controls both reproduction and calcium production. Ocs are therefore endocrine disruptors (= disrupt hormone balance). 

So birds reproducing less and as need a lot of calcium for their eggs were greatly affected. 

Dieldrin, PCBs and DDT stimulate P450 (so the three main groups of chlorinated hydrocarbons) P450 was then switched on and stated metabolising oestrogen inappropriately  level of oestrogen went down causes a lower production of Calcium (Ca) so reduced ability to make eggshells; and reduces reproductive activities  DDE inhibits the enzyme carbonic anhydrase which controls the uptake of Ca by the oviduct results in thin shells, broken eggs  Dieldrin is toxic to embryos 

DDT no very toxic to vertebrates and humans, but is to birds. 

Lindane still in use today to treat roofs, not known to affect birds but bioaccumulates in bats – 30 years half-life. 

100,000 tonnes of DDE estimated to be in ecosystems, will persist for another 100-200 years. Detectable in all animals, human milk. 

This highlighted the difficulty of first realising there is an environmental problem; and second on how difficult it is to prove a causal relationship as even if have circumstancial evidence it might be impossible to establish the relationship. Here for example, awareness of the problem happened by observation that birds were declining and that it seemed odd enough for someone to investigate but it took another 15 years befor it was noticed that the eggshells were thinning; also the survey on eggshell thickness was only possible as some historical collections existed.  

Chlorinated hydrocarbons: Organochlorine pesticides (OCs) thus DDT, DDD and DDE, Polychlorinated Byphenols (PCBs) linked to endocrine