Toxicology 3 Flashcards
T-f– most areas of USA have arsenic levels below .01mg/L. What is considered high?
T
>1mg is high
What does to much arsenic come from?
coal combustion and non-ferrous smelting
What form of Arsenic is the major toxic form?>
AsIII
[sodium arsenate is example NaAsO2]
What is the main use of arsenic?
pesticides
[other includes medicine, computer chips, glassware and paints]
What is the main ingredient in ant poison?
arsenic trioxide- tasteless…use for homicides
What keeps the high levels of arsenic in fish at check?
bound to betaine and is harmless and urinated out
T-F- arsenic is the 3rd most common cause of heavy metal induced death in the USA?
False- 2nd
What is the major routes of arsenic uptake?
GI and lung
What is arsenic half life=
3 days
What are the normal arsenic blood levels?
.03-.05 micrograms per dL
Total body burden is 1-10 mg mostly in skin hair and nails
Where is short term accumulation of arsenic?
liver, kidney, heart, and lung
Where is the long term storage of arsenic?
hair, nails and skin (affinity to keratin, SULFHYDRYL GROUPS!)
There is deposition in bones and teeth
What is the major route of arsenic excretion?
(sweat, hair, nails, teeth) > feces >urine
What is the mech of arsenic toxicity?
accumulates in mitoch. and inhibit mitoch enzymes w/ -SH groups
What are target organs of arsenic toxicity?
GI, Kidney, skin,
CV, nervous
What is dimercaprol and penicillamine used for?
chelation therapy in arsenic toxicity
T-F– arsenic toxicity leads to vasoconstriction?
False- dilation
What are mouth symptoms of arsenic?
burning lips, garlic breath, constriction of throat.
Review what chronic arsenic exposure does?
muscle weakness perspiration, skin pigmentation, dermatitis numbness, burning feet soles, vasodilation, heart arrhythmias ischemic gangrene Cancer reproductive tox
T-F 13 million live with > 10 micrograms As/L
True
Is cadmium bioaccumated?
yes, we take up more than we can excrete
Where is cadmium released from?
coal burning, Zn missing smelting
[used in electroplating, galvanizing, NV-Cd batteries
4. color pigment
What is the normal daily uptake of cadmium?
10-40 microgram / day
where is most of the body burden for cadmium?
kidneys>liver
what haooens in acute oral cadmium exposure?
nausea, vomiting, death
What happens in acute respiratory exposure to cadmium?
pneumonitis, pulmonary eema, death
What is the treatment for cadmium toxicity?
none- support lung function
What happens in chronic chronic lung cadmium exposure? cardiovascular? bone?
- COPD, BRONCHITIS, EMPHYSEMA
- HYPERTENSION
- PAIN, OSTEOMALACIA (Itai-itai disease japan- Ca metabolism disrupted due to damage)
What type of cancer doe cadmium exposure cause?
prostate (and lung, testes, kidney, stomach)
What happens to the kidneys with chronic cadmium exposure?
renal tubular disease, proteinuria, Fanconi’s syndrome.
What is the T1/2 of cadmium in humans?
10-30 years—> accumulate it with age
Do we have a biological need for lead?
no
Where does most lead toxicities come from today? 2
- paint, lead dust in households
2. recreation: shooting (and jewelry, stained glass, pottery, paint)
how many US children are at risk for lead poisoning?
100000, blood lleve > 10 micrograms/dL
Is lead problems worse in children?
yes their absorption is 41% and retention is 32% whereas adults are just a little over 5%
Where is lead sequestered in body?
RBCs
Doe lead replace Ca in hydroxyapatite in the bone more in children or adults? soft tissue?
- adults is 90% and children is 70%
2. 5%adults, 30%childrne
How is lead secreted?
urine, milk , fetus
can lead pass BBB?
yes
is lead readily stored, absorbed and mobilized?
yes
Does led have a cumulation burden?
Yes
IS there a large margin between population levels and toxicity for lead?
No- narrow margin
What is t1/2 of lead in soft tissue? bone?
- 28-36 days
2. 15-30 years (also a component of hair and nails as it combines with sulfhydryl groups
Acute lead poisoning in children causes what?
growth retardation, behavioral and lowered IQ problems
Whaat are the 4 keys parts of lead pathophysiology?
- binds sulfhydryl groups
- disrupts mitoch function
- disrupts Ca dependent intracellular messengers
- Inclusion bodies with a lot of lead
why do children have higher blood levels of lead than adults?
less goes to bone for storage
where does mercury naturally occur?
earth crust
when is mercury released?
coal burning, chlorine processing, waste incineration, and metals
What are the estimates for increased in atmospheric Hg due to humans?
2-3x or 1.5% per year
Does mercury display biomagnification of aquatic ecosystems?
yes
What form of mercury can bioaccumulate in fish?
methylmercury
what are CNS side effects of mercury?
constriction of vision, hearing loss, sensory disorder, ataxia, central disequilibrium
Does mercury damage the kidney? heart? what does it do in prenatal exposure?
- yes
- yes
- retardation, blindness, cerebral palsy like syndrome
What is the body burden of mercury that leads to damage?
15-35 g
we intake 3-7 mg /day
What is the T1/2 of methyl mercury? what does this lead to?
70 days and it leads to bioaccumulation.
How many women have more mercury in blood stream than EPA considers safe?
8%
Review the following recommendations on seafood for women and children
- do not eat shark, swordfish, king mackerel, or tilefish
- eat up to 12 ounces a week of seafood low in mercury- shrimp, canned light tuna, salmon, pollock, catfish, WHITE TUNA HAS MORE MERCURY THAN CANNED
- check local advisories about the safety of fish caught
Where do we get mercury in dentistry?
vapors from scrap amalgam are extremely dangerous [can not be discarded as regular trash] Its safety in dental fillings use is very controversial
What are 4 key characteristics of POPs?
persistent, highly toxic, evaporate and travel long distances hot to cold climates, accumulate in fatty tissue
What is trying to eliminate POPs from our environment?
Stockholm convention
What is dieldrin?
halogenated/cyclodiene- used against termites, textile pests, insects in agriculture
What is chlordane?
halogenated/cyclodiene- used against termites, broad spectrum
What is toxaphene?
halogenated/cyclodiene- applied to cotton, grains etc. and used against ticks and mites
What are the CNS effects of cyclodiene?
antagonize GABA r, uncontrolled state of excitation, dizziness, headache, convulsions, jerking
What are the GI effects of cylodienes?
nause, vomit, induction of liver enzymes C P450s etc
Can cyclodienes be absorbed through intact skin? carcinogenic?
yes
yes
What are polychlorinated biphenyls?
halogenated industrial compound- used for electrical equipment, prevents overheating, used in papers, sealants, plastics
Review the uses of PCBs?
capacitors, transformers, plasticizer, surface coatings, sealants CAULK, adhesive cutting oils, pesticide extenders, carbonless paper
Where are we exposed to PCBs?
- food (bioaccumulation/biomagnification)
2. Air (outdoors, old buildings)
When was production of PCBs banned in US?
1970
When are new PCBs continuously produced?
bi products in paint (when green paint isn’t green
What is a major PCB effect on the skin?
chloracne
What are the major PCB effects on the endocrine system?
disruption–> anti-estrogen/androgen, disrupts thyroid hormone homeostasis, OBESITY, METABOLIC SYNDROME, T2 diabetes
What is a chemical that causes a hormonal imbalance by out competing the body’s natural hormones?
endocrine disruptor
[causes reproductive and preg. problems, lactation prob, neurodevelopment problems, intellectualproblems in children, etc.]
What are PBDEs?
polybrominated diphenylethers– bromine flame retardants
penta, octa, deca
Where are PBDEs used?
electronic equipment, polyurethane foams, hard plastics
What country has the highest PBDE in human breast milk?
US then Canada
from flame retardant use in carpets
What are PDBEs toxic effects in humans?
unknown
possibly carcinogenic
[long term exposure has a greater effect than short term toxicity as the build up in your body]
How much of the body burden of a nursing mother is thought to be given to their child?
1/2!!!!
