DOSAGE & TOXICITY

1. DOSAGE & TOXICITY

2. A lack of understanding of these principles can lead to improperly labeling as toxic ingredients that are beneficial when used in the proper doses. • Every natural substance that is used for therapeutic benefit also has a toxic dose. • Even medications often found at a pharmacy or grocery store shelves have a dose at which toxicity occurs.

3. For example, Vitamin C (as well as • some of the other compounds in citrus fruit) will cause diarrhea (腹瀉), stomach upset (反胃), and even vomiting (嘔吐), if ingested in extremely large amounts. While this might be toxicity, no one would suggest that vitamin C should never be used for therapeutic benefit.

4. All substances have what is termed an LD50 (半數致死劑量). • This is the dose that, when administered to a large group of animals (or humans), will cause lethality (death) in 50% of that group.

5. If the LD50 is less than the average therapeutic dose, then toxicity occurs before therapeutic effects and the substance should be avoided. • If the LD50 is much greater than the therapeutic dose, then the substance is very safe and can be administered to a patient in large amounts without fear of toxicity.

6. Penicillin, which has an LD50 approaching infinity and a therapeutic dose that is much lower. • If LD50 is very close to the average therapeutic dose, then the medicine must be managed carefully. • Digoxin (地高辛) is a medicine commonly used for some heart conditions, congestive heart failure, and to regulate the heart rate.

7. Propylene glycol (丙烯乙二醇) is used in antifreeze and it should never be used on the body in any form. • The natural hormones (such as progesterone (黃體激素), estrogen (雌激素), DHEA (青春素), or testosterone (睪丸素) ) are placed in a pharmaceutical base containing propylene glycol because it is one of the very best substances for increasing absorption of natural hormone through the skin.

8. In fact, if Propylene glycol were not used, the medicine would not be absorbed effectively.#

9. Units used to measure chemicals in the environment • ppm: parts per million 1 cent in $ 10, 000 • ppb: parts per billion 1 cent in $ 10, 000, 000 • ppt: parts per trillion 1 cent in $ 10, 000, 000, 000

10. Important Relationship • For water at STP (standard temparature [23C] and pressure [15psi]) • 1cc = 1ml = 1g

11. 1 liter of water = 1 kg • 1 mg / kg = 1 ppm • 1 mm3 / liter = 1 ppm • 1 mg / liter = 1 ppm

12. Measures of Toxicity • Toxicity of chemicals is determined in the laboratory. • The normal procedure is to expose test animals by ingestion, application to the skin, by inhalation, gavage, or some other method which introduces the test item into the body.

13. Toxicity is measured as clinical “endpoints” which include: • Mortality (death) • Teratogenecity (birth defects) • Carcinogenicity (cancer) • Mutagenecity (DNA damage)

14. The Median Lethal Dosage(LD50 and LC50) • LD50 The dose ofa chemical which produces death in 50% of a population of test animals to which it is administered by a specified method. Normally expressed as mg/kg (milligrams of substance per kilogram of animal body weight)

15. LC50 • LC50 The concentration ofa chemical in air or water which produces death in 50% of an exposed population of test animals in a specified time frame. Normally expressed as mg/kg (milligrams of substance per liter of air or water [or as ppm])#

16. Routes of exposure (暴露途徑) • There are three primary routes by which organisms are exposed to certain material (solvents, pesticides, )： • Oral (口服) ：Taken in through the mouth and passes through gastrointestinal tract. • Dermal (皮膚)：Most common route of human exposure. • Inhalation (呼吸)：Breathed into the lungs through nose or mouth.#

17. Duration of Exposure (持續暴露時間) • Three terms are commonly used to describe the duration of doses： • Acute (急毒性)：Application of a short-term [generally less than a day] dosing. • Chronic (慢性)：Repeated exposure to a chemical in doses regularly applied to organism for a time greater than half of its life-expectancy. • Subchronic (亞慢性)：

18. The less you need to cause a toxic effect, the more toxic the substance is. Thus, an LD50 of 15 mg/kg is more toxic than is one of 250 mg/kg.#

19. Signal words (警語標示) • Caution (小心)：Reflects the lowest degree of relative toxicity. All pesticides with an LD50 > 500 mg/kg must display this word on their label. Actually includes two groups: 500 - 5,000 mg/kg (slightly toxic, 輕毒性) > 5,000 mg/kg (relatively nontoxic, 相對無毒性)

20. Warning (警誡)： Reflects an intermediate degree of relative toxicity. All pesticides with an LD50 that is 500 > LD50 > 50 mg/kg must display this word on their label. Pesticides in this category are classified as “moderately toxic (中等毒)”

21. Danger (危險)： Reflects the highest degree of relative toxicity. All pesticides with an LD50 < 50 mg/kg must display this word on their label. Pesticides in this category are classified as “highly toxic (劇毒)”

22. Poison (毒物)：Any pesticide with an LD50 < or = 50 mg/kg , the label must have the signal word “DANGER” plus the word “POISON”. • Also, the label must display the skull and crossbones icon.

24. Organisms can’t differentiate between “natural” and “synthetic” chemicals. • “synthetic (合成)” does not mean toxic or poisonous. • “natural (天然)” does not mean safe or even low risk. • Chemicals must evaluated in their biological context of behavior in organisms.

25. Mode of action, not source, is the concern and informed the users of pesticides. • Most herbicides act on biological pathways not present in humans.#

26. Insecticides (殺蟲劑) • TCDD (Dioxin) 0.1 mg/kg • Parathion (巴拉松) 13.0 mg/kg • Nicotine (尼古丁) 50.0 mg/kg • Carbaryl (加保利) 270.0 mg/kg • Malathion (馬拉松) 370.0 mg/kg

27. Herbicides (除草劑) • Paraquat (巴拉刈) 95 mg/kg • 2,4-D (二四地) 375 mg/kg • 2,4-DP (N/A) 532 mg/kg • Triclopyr (三氯比) 630 mg/kg • Dicamba (N/A) 755 mg/kg • Hexazinone (N/A) 1,690 mg/kg • Glyphosate (嘉磷塞) 4,320 mg/kg

28. Highly Toxic (劇毒) • Botulinus toxin 0.00001 mg/kg • Dioxin 0.1 mg/kg • Parathion 13.0 mg/kg • Nicotine 50.0 mg/kg

29. Moderately Toxic (中等毒) • Paraquat 95 mg/kg • Caffeine 200 mg/kg • Carbaryl 270 mg/kg • Marathion 370 mg/kg • 2,4-D 375 mg/kg

30. Are all substances toxic? • All are toxic to some degree. • Sugar has an LD50 of 30,000 mg/kg. • Ethanol has an LD50 of 13,700 mg/kg. • Even water has a recognized LD50 of slightly > 80,000 mg/kg. • All materials should be treated with care and proper respect!!!