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Basic Toxicology


1) What are the main local toxic effects caused by exposure to (contact with) organic solvents?

Local contact with organic solvents can cause defatting of skin (loss of protecting), local irritation and inflammation (skin red, warm, maybe swollen, maybe tingling = paraesthesia), and under rare circumstances chemical burn (necrosis).


2) Describe the meaning of the toxicological term ‘target organ’.

The (primary) target organ is the organ injured first when increasing the dose of a poison from a low level.


3) What is not a typical mechanism underlying chronic toxic effects?

A accumulation of agent due to its distribution into tissue with low blood perfusion rate
B accumulation of hydrophilic metabolites in blood plasma phase
C increase of activity of xenobiotics metabolising enzymes
D accumulation of DNA damage
E accumulation of subclinical cellular damage (e. g. continuous demyelinisation of neuronal axons)

B is correct answer


4) Describe the meaning of the toxicological term ‘receptor’ and give two examples.

The (cellular/body) molecule that interacts with the toxic agent and causes the molecular or cellular reaction that finally leads to poisoning is called receptor. Often (but not in any case) the receptor binds the toxic agent with high specificity, even if the free concentration is very low.

The receptor can be a protein, DNA, a phospholipid or a small molecule with own biological activity.

 

5) What ist the most leading cause of malformations or mental retardation of children during pregnancy in Europe?

Chronic ethanol consumption of the mother before and during pregnancy.

 

Pesticides A


1) Describe the basic principles of (allergic) chemical sensitisation.

At first exposure to a chemical agent the immune system (of some, not all human bodies exposed) starts to develop antibodies against the agent. Typically the patient does not suffer from any symptom within this sensitisation phase.

At subsequent exposures typical symptoms develop, either mainly respiratory (immediate type allergy: e.g. spastic bronchial muscle contraction = bronchial asthma) or dermal (delayed type allergy: contact dermatitis: inflammation of skin)

 

2) Describe the first two steps of the (classical) 3-step-model of chemical cancerogenesis

First step ‘initiation’: DNA alteration leading to mutation (non no-effect level, in principle one molecule can hurt)

Second step ‘promotion’: unspecific stimulus of cell proliferation (cell division) leads to deregulation of growth control in initiated cell(s) and tumor formation (for many cancerogens a no-effect-level can be derived)

(Thrid step 'progression': further mutions, metastasis)

 

3) What are the most typical symptoms of severe oral paraquat ingestion?

Initially local chemical burn of esophagus and stomach, leading often to cardiovascular dysregulation and shock. After a latency period pulmonary fibrosis (developing after 10 days or more)

 

4) What is the molecular mechanism underlying chlorophenoxy carbonic acid poisoning (e. g. 2,4,5-T = ‚Agent Orange’)

Heat production caused by decoupling of mitochondria.

 

5) Describe the cause and circumstances of the 1971 Iraq Poison Grain Disaster?

Seed grain treated by fungicidal methyl mercury was consumed as food (bread) by error (Spanish label and warning colour were not understood).

 

Pesticides B

 

1) What enzyme is inhibited by organophosphate insecticides?

Acetylcholine esterase in neuronal synapses.

 

2) Describe three typical symptoms of organophosphate insecticide poisoning!

Increase of bronchial secretion, breathing difficulties, heart rate decreased, colic pain in stomach, pinpoint pupils

 

3) What is the reason that nine insecticides are banned by the World Health Organisation (WHO) today?

The banned insecticides (ALDRIN, CHLORDANE, DDT, DIELDRIN, ENDRIN, HEPTACHLOR, HEXACHLORBENZOL (HCB), MIREX, TOXAPHENE) are very persistent in the environment and accumulate in the human body (fat and breast milk).

 

4) Give 3 examples for insecticides banned by the World Health Organisation (WHO).

ALDRIN, CHLORDANE, DDT, DIELDRIN, ENDRIN, HEPTACHLOR, HEXACHLORBENZOL (HCB), MIREX, TOXAPHENE

 

5) What is the symptom typically caused by pyrethroids in man?

Paraesthesia (tingling, local, perioral), anaesthesia

 

6) What is the mechanism of pyrethroids toxicity?

Suppression of neuronal signal transmission caused by interaction with sodium channels in neurons