Week 7 Flashcards
Metals
More toxic as soluble ionic form or organometallics.
Increased absorption, accumulation in tissues; slow excretion
- Toxic responses involve:
- many organs i.e. CNS, liver, kidney, cardiovascular & reproductive systems, G.I. tract & skin
- route-specific e.g. Ni dust – inhaled (lung cancer), swallowed (liver damage) or on skin (allergies)
- many are carcinogenic e.g. Ni, Cd (genotoxic activation-independent inorganic carcinogens)
Reactive Oxygen Species & Protective Pathways
Transition Metals (Fe, Cu) catalyse Fenton Reaction.
Protective pathways: SOD, superoxide dismutase; CAT, catalase; GSH Px, glutathione peroxidase
Pesticides
Generally have acute & chronic effects on nervous system
* Toxic heavy metals and metalloids (e.g. lead arsenate) were widely-used in early mass agriculture – now replaced by Organochlorine pesticides
Organochlorine pesticides
DDT, dieldrin
- very lipophilic & persistent
- some are immunotoxic & carcinogenic (promoters)
- tend to bioaccumulate & bioconcentrate in the foodweb
Organophosphates (OP) & carbamate esters
inhibit acetylcholinesterase (AchE) on neuronal post-synaptic clefts (“aged AchE”)
- Many need metabolism by cytochrome P450 (CYP) to active forms eg.(malathion malaoxon)
Pyrethroids
based on natural pyrethrins
least persistent pesticides (but can cause neurological disturbances)
Neonicotinoids
- stable hydrophilic systemic pesticides*; uptake & transport to all plant tissues (different to surface contact pesticides)
- selective for invertebrate CNS (less toxic to birds & mammals, but toxic to beneficial insects, e.g. bees; low dose stim., high dose paralyses)
Aromatic hydrocarbons
Produced in many industrial processes
(adhesives, detergents, polymers, pesticides, cigarette smoke & fuel)
Many “endocrine disruptors” causing hormonal disruption
Polyhalogenated aromatic hydrocarbons (HAHs)
- Fat soluble and persistent
- Have numerous toxic effects including:
carcino- & terato- genicity; hepato-, neuro- & immuno- toxicity; potent tumour promoters - Includes:
fire retardants/heat exchangers
polychlorinated biphenyls ‘PCBs’
polybrominated biphenyls ‘PBBs’
hexachlorobenzene
eg. Furans, Dioxins
Polycyclic aromatic hydrocarbons (PAHs)
- Formed from incomplete combustion of organic matter
- Ubiquitous environmental contaminants
- Some are potent carcinogens and immuno-suppressants
- PAHs & HAHs bind the aromatic hydrocarbon (Ah) receptor
- specifically inducing CYP1A enzymes to enhance toxicities of other xenobiotics (by increasing metabolic activation)
Most carcinogenic PAHs must first be converted to reactive metabolites
Acute adverse effects of solvents
interfere with nerve function.
Used in confined spaces causes acute CNS-depressive effects:
Disorientation, euphoria, giddiness, confusion, progressive loss of consciousness, paralysis, convulsion, death
Chronic adverse effects of solvents
Neurotoxicity:
Sensory - e.g. visual, auditory
Cognitive - e.g. memory, confusion, disorientation
Affective - e.g. depression, apathy, nervousness
Motor - e.g. fatigue, tremor, in-coordination
Chlorinated solvents
Uses: paint removal, metal degreasing, cleaning
Acute: Irritant, liver, kidney, CNS depression, heart (arrythmias), lung (oedema)
Chronic: Fatigue, anorexia, liver, kidney; cancer (animals, non-genotoxic)
Aromatic solvents (benzene)
Uses: Rubber industry; paints, plastic & chemicals manufacture
Acute: CNS depression: nausea, ventricular arrhythmia, respiratory depression
Chronic: Headache, anorexia, weariness
Glycol ethers
Uses: resins, printing inks, textile dyes, varnish removers,
Acute: Irritant, nausea, liver, kidney
Chronic: Reproductive toxicity (male animals); developmental toxicity
(animal teratogen)
