Chem. 253 – 5/13 Lecture

Announcements I• Return HW and Group Assignments• Turn in Toxicology HW (last homework)• Today’s Group Assignment on Alternative Fuel

and Toxicology• Final Exam

– Scheduled for Wednesday, 5/20 5:15 to 7:15 PM– Not cumulative and same percent toward overall

grade as exam 1 and 2– will give you 2 hours

Announcements II• Today’s Lecture

– Review of Last Week’s Topics– Additional Toxicology (Redistribution and Fate of

Substances)– Review for Final Exam– Skipping Soil Chemistry Section (due to failing voice

+ limited time)– Will have two sets of teaching evaluations (one for

me and one for Justin)– Any comments on the group activities would be

appreciated

Biofuels- Review

• Rationale for Interest in Biofuels– Reduction in CO2 production with fuels from

renewable resources

– Oxygenated fuels are also cleaner burning

– Fuels as waste products (used cooking oil and cellulose) reduce overall resource use

• Limitations:– Problems from using high % renewables in fuel

– Land requirements are high if % of fuels from biofuel sources is significant

– Competition with food

Biofuels- Review

• Fuel Issues– Ethanol feedstocks• food competitive (starch and sugar)

• cellulose (large % of ag waste)

• feedstock affects viability and competition

– Biodiesel feedstocks (vegetable oils and fats)• storage/use issues (decomposition and precipitation)

• higher NOx emissions

Toxicology- Review of Exposure Section

• Exposure – Three main routes• Dermal – contact with liquids, gases or

solids• Inhalation – typically major problem

with gases and aerosols• Oral – inadvertent ingestion or

contamination of food or drink

Toxicology- Review of Exposure Section

• Exposure – What matters beyond concentration and entry route– Form of Toxic Substances Matter• Phase of molecule• Polarity of molecule• pKa for acids or bases

– Exposure Time

Toxicology- Review of Dose-Response Section

• Typically Multiple Responses• Variability of Effect on Subject is

Common• LD50 occurs in middle of distribution, but

distribution can depend on factors• Steepness of response curve affects range

of concentrations inducing an effect• Exposure must be set low enough not to

generate effects at low concentration end of response curve

Toxicology - Redistribution in Body

• Movement to target organs/tissue (e.g. Hg to nerve tissue)

• Storage Tissue/Organs– fats (for compounds with large Kows)

– bones (for certain inorganic compounds)

• Organs with High Concentrations:– Liver + Kidneys– Normal because these organs used for

chemical transformation (liver) or excretion (kidney)

Toxicology - Fate of Substances

Toxic compounds in the body can be: 1) excreted or 2) transformed

Water soluble compounds tend to be excreted more quickly, while lipid soluble compounds can have long lifetimes (months)

A common transformation is enzymatic oxidation in the liver (particularly for lipid soluble compounds)

Oxidation can lead to decreases or increases in toxicity, but usually leads to faster excretion due to increase in polarity

Toxicology - Fate of Substances

• Some Common Transformations:– Hydroxylation– Dealkylation (alkyl

groups attached to N, O, or S)

– Oxidation– Epoxidation– Glucuronic Acid

Addition

OH

RNHCH3 RNH2 + CH2O

RCH3 RCH2OH RCH2O

RCH=CH2RCH--CH2

ORC(OH)HCH2OH

O

O

OHH

HH

OHOH

H OH

H

OH

OH+

O

O

OH

HH

OHOH

H OH

H

OH

Toxicology - Fate of Substances

• Hypothetical Example– Moderately polar compound (compound A) is

slowly eliminated and transformed to product (compound B)

– Compound B is eliminated faster than compound A (Only reaches low concentration)

Time

Conc. A – elimination only

A – transformation onlyA – both losses

Compound B

Toxicology - Removal of Substances

• Polar/Water soluble compounds are often eliminated through urination

• Volatile compounds can be eliminated by exhalation

• Less polar compounds can be removed from liver through bile (goes back to GI tract)

• Other routes– GI tract– Sweat

Toxicology - Biotracer Studies

• Exposure is often difficult to assess accurately– Example: wood smoke in winter– can measure outdoor concentrations (but it is variable

under inversion conditions)– many people are inside (indoor concentrations are lower)– people exercising under high pollution conditions (early

evening running) are likely to be exposed to much higher concentrations than to others

• An alternative approach is to directly measure concentrations of toxin or metabolites in urine

• Factors affecting exposure then can be studied by comparing environmental concentrations with detected amounts

Break for Group Activity

Toxicity- Types of Effects

• Acute Effects– exposure period is typically short but intense– effects occur soon after exposure– effects may be reversible or irreversible

• Chronic Effects– exposure period is typically over a period of time– effects generally take time to develop (e.g. cancer)– may occur from build up of product (e.g. calcium

oxalate from ingestion of ethylene glycol)– may result from body’s reaction to toxin (e.g. build

up of scar tissue)– may occur for low probability effects (mutation of

DNA)– determining relationship is more difficult

Toxicity- Chronic Effects

• Teratogens– Compounds that affect normal

development of fetuses

• Mutagens– Cause changes to DNA sequences

• Carcinogens– Compounds that can lead to the

development of cancer

Toxicity- Chronic Effects

• Effects of Carcinogens– Most carcinogens (or their metabolites) can

react with and alter DNA– Carcinogens may react with base pairs (e.g.

aromatic compounds) or with sugar or phosphate parts

– Many changes to DNA sequence have little effect (may kill cell or have minor effects)

– Changes to DNA can affect normal mechanisms to restrict cell growth

– Proliferation of deformed cells is what leads to problems with cancer

Toxicity- Chronic Effects

• Determination of Carcinogens– Epidemiological Studies (comparison of

environmental exposure with effects on population)

– Animal Tests (e.g. feeding compounds to rats or mice)

– Ames Test (bacterial screening test for mutagens)

Toxicity- More questions

1. The LD50 for paraquat is about 100 mg/kg. Estimate the amount of paraquat that would need to be ingested by a “typical” 50 kg woman to just die from it.

2. Why might it be prudent to limit exposures of toxic compounds to several orders of magnitude under the LD50?

3. What are possible metabolic products of CH2=CHCH2OCH3?

4. Regulations often limit toxic substances through a) absolute concentration limits and b) time averaged concentration limits. Why would two separate limits be useful? What are the two limits protecting against?

Exam 3- Topics to know

I. Climate Change• Be able to balance solar light in with infrared light out (with and without albedo considerations)*• Blackbody emissions (total flux as a function of T* and wavelength dependence)• Understand main absorbing species in the atmosphere for solar radiation and infrared radiation• Understand effect of increasing greenhouse gases on radiation balance• Requirements for a molecule to be able to absorb in IR and basis for relative effectiveness of different gases

* Need to be able to perform calculations

Exam 3- Topics to know

I. Climate Change – cont.• Main causes for increases in main greenhouse gases (CO2, CH4, N2O, CFCs)• Differences between long-lived greenhouse gases (those above) and other climate affecting compounds (ozone and aerosols)• Direct and Indirect aerosol effects on climate• Concepts of positive and negative feedbacks on climate• What sensitivity refers to

Exam 3- Topics to know

II. Fuels and Energy• Major uses of energy• Why requirements for different fuels depend on use• Three main fossil fuel sources• The significance of energy efficiency (heat per mol of CO2 generated)• The basic strategy in carbon capture

III. Green Chemistry• Main Goals of Green Chemistry (see slide 8)• Should know several of the 12 principles

Exam 3- Topics to know

III. Green Chemistry – cont.• Be able to judge how specific principles apply to alternative syntheses and products (e.g. hazard assessment if MSDS type information is given)• Be able to calculate atom economy*• Some of the major types of changes to make a process or product “greener” (product, solvent, feedstock, energy requirements)

IV. Biofuels• Rationale for Use and Limitations• Feedstock sources• Secondary advantages of fuels

Exam 3- Topics to know

V.Toxicology• Concept of Exposure• Routes of Entry + issues with these• How form of compound affects toxicity• Meaning of LD and Dose – Response Plots (plus be able to read)• Two major routes of toxic compound transformation and elimation• Common transformation reactions and their effects on toxic compounds• Differences between acute and chronic effects• Definition of carcinogens, teratogens, and mutagens• Methods of determining carcinogens