Lecture 5 – NPs, ecotoxicology and the public concern about chemicals

in the environment

Lecture 5 – NPs, ecotoxicology and the public concern about chemicals in the

environment

Sherlock Holmes ponders  "the curious incident of the dog in the nighttime."

Watson, surprised, responds,"But the dog did nothing in the nighttime."

"That was the curious incident," Holmes replies

Arthur Conan Doyle, Silver Blaze

Learning outcomes • why any discussion of chemicals in the environment can be greatly enriched by thinking about NPs …

• the growth in public concern about “pollution”

• toxicology “fails” but did ecotoxicology succeed?

• why it might be useful to build a new, broader view on the issues that are of interest to "ecotoxicologists“ – biomolecular toxicology?

• what have NPs to do with this … am I in the wrong lecture?

• you should leave with a new insight into why we need to rethink our ideas about ecotoxicology

The changing attitudes to drugs and agrochemicals

Pre 20th C• very limited use of manufactured chemicals

End 19th C and very early 20th C• significant use of manufactured chemicals in agriculture. • mainly toxic metal salts – lead, arsenic, mercury, copper, etc..Early laws to protect consumers from contaminated foods. Fictional use of poisons for murders.• HCN used to fumigate fruit trees. First know case of pesticide resistance.• use of poisons in medicine also common – selective application or uptake, not selective toxicity

The changing attitudes to drugs and agrochemicals

1910-1940 The discovery of selective toxicity – scientists marvel and dream

• Erlich’s pioneering work on highly selective action of drugs• The discovery of the antibiotic penicillin• First synthetic selective fungicides discovered• First synthetic selective herbicides discovered (2,4-D)• First synthetic highly selective insecticides discovered (DDT)

1940-1960 The widespread adoption of new “safe” drugs and agrochemicals – the public love them.

• The growth of the pharmaceutical industry • The growth of the agrochemical industry• The belief that major diseases would be irradicated by vaccination, drugs and pesticides

The changing attitudes to drugs and agrochemicals

1960-1975 What is safe? Safe for humans? Safe for other organisms?

• 1962 Rachel Carson’s Silent Spring - DDT and organochlorines• 1960-1970 Agent Orange (2,4-D and 2,4,5-T) in Vietnam war• Early 1960sThalidomide – drug to treat morning sickness• Scientists begin to worry more about non-target organisms

DDT – the good, the bad and the ugly

The changing attitudes to drugs and agrochemicals

1975-2005 The widespread use of drugs and agrochemicals but public sceptism still very high

• Greater demands on companies to assess all risks• Industry consolidation• GM crops – better or worse?• The affluent public in many developed countries increasingly adopt Organic Foods and “natural” or “no artificial colouring” becomes common on labels ………. the public fear is a sales opportunity.

1950 1965 1980Toxicology Acute toxicity (LD50) Acute toxicity (LD50) Acute toxicity (LD50)

30-90 d rat feeding 90 d rat feeding 30-90 d rat feeding90 d dog feeding 90 d dog feeding2 y rat feeding 2 y rat feeding1 y dog feeding 2 y dog feeding

Reproduction in 3 rat generationsTeratogenesis in rodentsToxicity to fishToxicity to shellfishToxicity to birds

MetabolismNone Rat Rat and dog

Plants

Residues Food crops 1ppm Food crops 0.1 ppm Food crops 0.01 ppmMeat 0.1 ppm Meat 0.1ppmMilk 0.1 ppm Milk 0.005 ppm

Ecology None None Environmental stabilityEnvironmental movementAccumulationTotal effects on all non-target species

The Growth of Public Concern about Chemicals EU Directive on Drinking Water Directive

> £1,200,000,000 capital costs and £100,000,000 pa running costs to achieve < 0.1 microg per litre of any any pesticide

Only 14 per cent of the chemicals used in high volumes in the EU today (over 1,000 tonnes per year) have got a basic set of safety data publicly available. The EU commission has proposed a strategy for a future Chemicals Policy, whereby some 100,000 different chemicals will be tested on animals.

REACH – the EU Policy on evaluation of the risks associated with the use of chemicals

“WWF and The Co-operative Bank took and analysed the blood of 47 people from all over Europe in December 2003. These included 39 Members of the European Parliament, 4 Observers from accession countries, 1 former MEP and 3 WWF staff, representing 17 countries in Europe. The results released on 21 April 2004 are unacceptable. It reveal that every person is contaminated with a cocktail of persistent, bio-accumulative and toxic chemicals including chemicals from each of the 5 groups of (...)”

Chemicals Industry - stop wrecking REACHReport reveals misleading and unsubstantiated statements by chemical industry

Brussels, 10 November 2005 - The European chemical industry has been progressively weakening the European Chemicals Reform (REACH), contrary to its publicly voiced support for the legislative proposal according to a report released today by Friends of the Earth Europe.

From FOE website

REACH – the EU Policy on evaluation of the risks associated with the use of chemicals

But how does any of this relate to NPs?

Biomolecular activity is a rare property for a molecule to possess

So the chances low doses of any one chemical, synthetic or natural, being harmful is very small

The list of chemicals mentioned in ecotoxicology textbooks rarely exceeds 80 ….

But how does any of this relate to NPs?

As Holmes might have said    " ..... the curious incident of the 80 chemicals mentioned in this textbook ..."

Watson feels obliged to comment  " .. but there is nothing curious about that list is there?"

Holmes   "Why are there only 80 instead of 80,000? Why do those 80 chemicals have their effect when the other 79,920 have no apparent effect?"

Watson     "Good heavens Holmes, the lesson from Silver Blaze again!“

Holmes   "Elementary my dear Watson, pass my favourite Natural Product ...."

Watson    "But Holmes old man, seeing you take the cocaine makes me think that one might increase that list to > 500,000 because there are organisms out there making chemicals as well."

Holmes   "Quiet Watson. I do the clever stuff around here ..."

But how does any of this relate to NPs?

Organisms have evolved to cope with chemicals in their food or in their environment

The NP diversity is greater than current synthetic chemical diversity

The quantity of NPs made every year is > 109 tonnes – maybe as much as total biomass of animals?

The world was never a chemically clean place.

Ecotoxicology and toxicology must take into account NPs

Ecotoxicology and toxicology should take into account NPs.

• How do NPs get broken down in the soil or water?

• There must be some very good means of breaking down chemical diversity otherwise over a period of 1 century the total mass of chemicals would be huge.

• How is it done?

• Microbes mainly … we think

• But why do they do it?

• A source of carbon, nitrogen or P?

• What implications are there for the breakdown of synthetic chemicals?

Do microbes degrade NPs (and synthetic chemicals) as a source of elements?

• Are microbes living on exotic chemicals simply accessing a source of carbon, nitrogen or P?

But why would a microbe select to grow on a low concentration of a NP when there are higher concentrations of other organic molecules in the soil or water?We know from laboratory studies that unless one maintains a high selective force on a microbial isolate capable of growing on an exotic chemical, mutants capable of growing on more easily metabolised chemicals take over.

Maybe microbial enzymes degrading exotics are NP producing enzymes with broad substrate tolerances – it is an accident unless selected for?

Animals … how do they deal with NPs (and synthetic chemicals)?

• Did the liver evolve to degrade toxins?

You ingest thousands of NPs every dayMost ingested NPs will have low biomolecular activity

Any chemical made by degrading one NP has the same low probability of possessing biomolecular activity – the fewer chemicals one makes the betterThe best strategy might simply be to make NPs water soluble and excrete them. That keeps the concentration of the chemical very low hence reduces the chance of significant biomolecular activity arising. The same broad specificity enzymes that do that will happily accept most synthetic molecules as well … including pharmaceuticals ..

Discussions of the way in which synthetic chemicals have their effects on the natural world must take into account the chemistry of the natural world – that means NPs

Summary

An understanding of the way in which organisms evolved to make and degrade complex natural chemicals is essential to the subjects of toxicology and ecotoxicology.

The principles outlined in the module so far are simple and could help the public and politicians come to terms with a subject that causes unnecessary worry and expense.

Horseradish root contains approx. 0.6% of glucosinolates; the most abundant of these are sinigrin (0.2%) and gluconasturtiin (0.1%). As soon as intact cells are damaged, these isothiocyanates are enzymatically hydrolyzed to yield allyl isothiocyanate and 2-phenylethyl isothiocyanate, respectively.

Horseradish

Ecotoxicology and toxicology must take into account NPs. many organisms can make chemical

diversity

many organisms can degrade exotic chemicals

why do they do that?

mammals - the liver? insects microbes - plants - the green liver?

how do they do that?

mammals - P450 cytochromes, etc. insects - P450 cytochromes, etc microbes - P450 cytochromes plants - P450 cytochromes, etc.