Toxic Effects of Chemicals

ALL CHEMICALS ARE TOXIC AT SOME LEVEL.ALL CHEMICALS SHOULD BE CONSIDERED TOXIC UNTIL PROVEN OTHERWISE.EVEN CHEMICALS WHICH ARE RELATIVELY “SAFE” CAN BE HARMFUL IN COMBINATIONS.

OSHA says hazardous chemicals are ones which are…

toxic, corrosive, irritants, strong sensitizers, carcinogenic, flammable or reactive, or

specifically listed by OSHA in 29 CFR 1910, Subpart Z, or

have been assigned a TLV by the ACGIH.

Toxicity of chemicalsDefinitions

Acute toxicity occurs from a single exposure and results in damage within a few days.

Chronic toxicity results from repeated, often low-level, exposures over months to decades. Effects may not appear until long after exposure has ceased.

Types of Chronic ToxicityMutagens act on DNA, genes or chromosomes of cells; may lead to death of the cell or cancer. If the cell is a sperm or egg, may lead to birth defects.Carcinogens are cancer-causing after a latency period.Embryotoxins cause problems for a developing fetus when the mother is exposed during pregnancy, includes teratogens.Fertility depressants are substances which lower the odds of conception.

Toxicology Studies

Routes of exposure

Transport within the body

Transformation within the body

Modes of attack

Storage

Elimination

Routes of Exposure

INHALATION

INGESTION

SKIN or MUCOUS MEMBRANE ABSORPTION

EYE ABSORPTION

INJECTION

Routes of Exposure (cont’d)Inhalation: vapors, mists, gases or dusts can produce irritation by contact and systemic poisoning by absorption into the blood stream. The most common [and usually most dangerous] route of entry. We breath 10 m3 of air every eight hours and this air comes in contact with 140 m2 of capillary surface.Ingestion: hazards as for inhalation. Generally of minor importance except for very toxic agents because of normal precautions taken with respect to eating, drinking, smoking, etc. in presence of chemicals. Chemicals are not as readily absorbed from GI tract as in lung. Can occur as a side effect of inhalation through cilliary action and swallowing.Skin and eye contact: hazards as for inhalation. Skin provides some protection but is the most common point chemical contact. Some solvents pass directly through the skin. The eyes are especially sensitive, acting like sponges to liquids and easily scratched by solids.Injection: can occur from cuts by contaminated materials such as broken glass or by accidental syringe wounds.

Dose-effect Curves

Biological organisms show differences in sensitivity to toxic materials. The variations are small within species compared to between species. A frequency of response curve would theoretically look like a “normal” distribution.

Dose-effect Curve

Dose

Num

ber

begi

nnin

g to

sho

w e

ffec

t

Cumulative Response Curve

It is more conventional to use a cumulative response curve to report toxicological data. The slope of the rising portion of the curve is related to the margin of safety. If the effect being plotted is death, it is an easy matter to obtain the LD50 from the graph.

Cumulative Response Curve

Lethal DosesCompound Test animal Route LD50 (mg/kg)

ethanol mouse oral 10,000

sodium chloride rat oral 3,000

aspirin rat oral 1,500

DDT rat oral 150

potassium cyanide rat oral 10

nicotine rat iv 1

dioxin guinea pig iv 0.001

botulinus toxin rat iv 0.00001

Some terms encountered which express toxicity verbally include:

extremely toxic LD50 <1 mg/kg

moderately toxic 50-500 mg/kg

relatively harmless >15000 mg/kg

Interactive Effects

Additivity – the total effect is the simple sum of the individual effects.Synergism – the total effect is greater than the simple sum of the individual effects.Antagonism – the total effect is less than the simple sum of the individual effects.Potentiation – one chemical has the effect of setting the organism up for an effect by a following chemical.

Epidemiological studies are carried out on large groups of human

subjects either retrospectively or prospectively

Strengths: natural exposures; long-term, low-level exposures can be found; no need to extrapolate from animals.

Weaknesses: many variables which cannot be controlled for; difficult to determine causation (as opposed to association)

Clinical studies are carried out on carefully controlled groups of human

subjectsStrengths: much more knowledge about exposure conditions, fewer uncontrolled variables, often-possible to assess cause-effect.

Weaknesses: artificial exposures, generally only acute studies, ethics of group control.

Toxicological studies are performed on animals, tissues, cells,

biochemicalsStrengths: maximum exposure control, exact response can be determined, cause-effect probably determinable.

Weaknesses: extrapolation to humans required when animals used, often difficult to study chronic effects due to short lifetime of animal subjects, ethics of subjecting animals to tests.

Exposure Limit Terminology

PEL = permissible exposure limit (OSHA). This may be given as a time-weighted average (TWA, for 8-hr shift over 40-hr week) limit, or a short-term exposure limit (STEL, not to be exceeded for more than 15 min. any time during a work day) or a ceiling limit (CL, not to be exceeded any time).

Exposure Limit Terminology

REL = Recommended exposure limit (NIOSH). Highest airborne level not expected to produce injury in workers, generally TWA for 10-hr day, but may be a CL.

IDLH = immediately dangerous to life (NIOSH). Maximum concentration which could be tolerated for 30 min. (in case of respirator failure) without impairing ability to escape or causing permanent damage.

Exposure Limit Terminology

AL = action level (OSHA). Exposure level at which OSHA regulations to protect workers (air monitoring, medical monitoring, etc.) kick in, generally half the PEL.

TLV = threshold limit value (ACGIH). Designed to protect “average” healthy worker. May be expressed in any of the same ways as PEL’s above. Traditionally were TWA’s.