1. Introduction to Chemical Hazards Eric Amster MD MPH Introduction to Environmental Health

2. Overview  Information on chemical hazards  Common types of exposures:  Metals  Solvents  POPs  Routes of chemical exposure

3. Sources of chemical hazards  Natural  Synthetic How many synthetic chemicals in production

4. 200,000+ synthetic chemical compounds  Impossible to know about toxicity of all of them.  Ask yourself three questions  What were the chemicals being used?  What is the actual exposure?  Concentration of chemicals  Amount  What is the route (dermal, inhalational, ingestion) of exposure?  Are exposure levels of specific chemical of health concern

5. Case Presentation

6. Occupational history  Factory worker with 4 years experience  Cleans metal parts of airplanes  Open work space  No PPE, no individual ventilation  Reports working with  Acetone, MEK, PRC Case Presentation

7. Medical history  29 years old, generally healthy  Quit smoking 3 years ago, non-drinker  No surgeries, medical problems, allergies  No prior pregnancies Question: Is it safe for her to continue working? Case Presentation

8.  What chemicals is she exposed to?  I.e. what is MEK and PRC  What is her actual exposure?  Route, amount  Are her exposure levels concerning for teratogenic effects? Case Presentation Spoke with safety manager and requested MSDS Requested information about industrial processes, monitoring data and PPE Searched through the relevant literature to determine toxicity profile

9.  Information supplied by manufacturer  Information edited by distributor  “Trade secret” not included  Limited and selective information MSDS

10.  9 pages long  Tox-line search  23,194 original articles published  Hazardous substance database (HSDB)  301 reviews published MSDS- PRC

11. MSDS

12.  487 articles on DART (developmental and reproductive toxicology databases) on teratogenicity of Manganese

13.  Information supplied by manufacturer  Information edited by distributor  “Trade secret” not included  Limited and selective information  Not consistent MSDS

16.  Information supplied by manufacturer  Information edited by distributor  “Trade secret” not included  Limited and selective information  Not consistent  Information is not always clinically relevant MSDS

17.  According to personal monitoring: exposed to 8 ppm of MEK

18.  NIOSH pocket guide Clinical resources

19.  NIOSH pocket guide Clinical resources

21. National Library Medicine- toxportal

23. Heavy metals  Naturally occurring and commonly used in industry  Most commonly from anthropogenic sources (human sources)  Lead  Mercury  Arsenic  Cadmium

24. Lead Most common cause of metal poisoning Common exposures:  Smelting (melting) lead: battery factories, metal recycling  Ammunition  Lead miners  Plumbers, auto mechanics  Paint before 1980’s, gasoline

25. Lead  Levels: Blood lead >10ug/dl is poisoning  Toxicity: Toxic to heart, bones, kidneys, reproductive and nervous system  Symptoms: abdominal pain, anemia, confusion, headache, seizure, come, death

26. Mercury  Common exposures:  Elemental mercury (only inhalation of the vapor is toxic): metal mining and smelting, laboratories, dental  Inorganic mercury (more bio-available)  Organic mercury (most available and toxic): fish consumption (shark, large tuna, swordfish)

27. Mercury  Toxicity: Brain, kidneys, lungs, neurologic  Symptoms: peripheral neuropathy, insomnia, memory loss, skin discoloration (facial), loss of hair, teeth, and nails. Impaired vision, hearing. “Mad as a Hatter”

28. Arsenic  Exposures:  Inorganic (more toxic form): well water, glass work, wood preservation.  Organic (less toxic form): pesticides on vineyards, antibiotics for poultry, fish in contaminated water.

29. Arsenic  Toxicity: lungs, skin, kidneys, liver  Symptoms: diarrhea, vomiting, hair loss, seizures, coma

30. Cadmium  Exposures: batteries, industrial paints (ships & trains), pesticides  Toxicity: lungs, bones, kidneys  Symptoms: “metal fume fever” (sorethroat, headache, dizziness, fever, chills), renal failuree, osteoporosis

31. Organic Solvents  A liquid (commonly) that dissolves another material.  Organic solvents used in almost all industries and are commonly found in home cleaning supplies and cosmetics.  Dermal, ingestion, and inhalation hazard.

32. Organic Solvents  Dry cleaning-- tetrachloroethylene

33. Organic solvents  Nail polish remover– acetone, ehyl acetate

34. Organic Solvents  Paint thinner--- toluene turpentine

35. Organic Solvents  Toxicity:  Nervous system: confusion, headache, loss of consciousness. Primarily from inhalation  Hematologic: anemia, leukemia  Liver: liver failure, liver cancer

36. Persistent organic pollutants  A class of chemical that are resistant to environmental degradation.  Organic compounds  lipophilic  Persist in the environment and accumulate in the body (bio-accumulate)

37. POPs  Toxicity: Endocrine and reproductive systems  Also known as “endocrine disruptors”  DDT, dioxin, and PCB linked with diabetes  Possible association with breast cancer  Possible association with decreased sperm count and infertility.

38. Bioaccumulation  The buildup of chemicals in the body.  Usually lipophilic and stored in fat tissue  Biomagnification: Accumulation through the food chain.

39. Bioaccumulation

40. POP “dirty dozen”  Aldrin  Chloradane  DDT  Dieldrin  Endrin  Heptachlor  Hexachlorobenzene  Mirex  Polychlorinated biphenyls (PCB)  Polychlorinated dibenzo- p-dioxin  Polychlorinated dibenzofurnas  toxaphene

41. POPs  DDT: dichlorodiphenyltrichloroethane:  Type of insecticide: organochlorine.  Used extensively in early 1900s to control malaria from mosquitos.

42. POPs  DDT: dichlorodiphenyltrichloroethane:  1962: “Silent Spring” by Rachel Carson discussed widespread use of DDT. Contributed to environmental movement.  Primarily effects wildlife, considered “moderately hazardous” by WHO.  Genotoxic, 2B carcinogen by IARC

43. IARC categories  International Agency for Research on Cancer  1A: Carcinogenic to humans  2A: Probably carcinogenic to humans  2B: Possibly carcinogenic to humans  3: Not enough information  4: Probably not carcinogenic in humans.

44. POPs  PCB: Polychlorinated biphenyls  A group of 209 different chemicals of different conformations.  Has two phenyl rings with multiple combination of chlorine atoms.  Primarily exposed through inhalation of gas in the air, ingesting contaminated food or direct exposure to the skin

45. PCB  Exposures: Fire retardant, adhesive, paints, water- proofing, PVC piping.  Symptoms: Chloracne  Liver and breast cancer  Menstrual irregularities,  Cognitive delay in children.

46. POPs  Dioxin: 2 oxygen molecules in center ring  75 different congeners  Toxicity: Endocrine disruptors, reproductive toxicity

47. Also includes  PAH (polycyclinc aromatic hydrocarbons)  32 different compounds  Toxicity is variable  Carcinogenic  Benzo(a)pyrene  1 st carcinogen discovered  Product of cigarette smoke, BBQ  Chronic lung disease  Acute neurological conditions

48. Also includes  Brominated flame-retardants  Found in furniture, electronics, carpets, clothing  Endocrine disruptor, reproductive toxicity, carcinogenic?

50. A Population-based Case– Control Study of Urinary Arsenic Species and Squamous Cell Carcinoma in New Hampshire, USA  Diane Gilbert-Diamond, 1,2 Zhigang Li, 1,2 Ann E. Perry, 3 Steven K. Spencer, 4 A. Jay Gandolfi, 5 and Margaret R. Karagas 1,2  Environ Health Perspect 121:1154–1160;

51. Scientific Background  Nonmelanoma skin cancer is the most common type of malignancy among whites  Chronic exposure to arsenic (As) has been associated with SCC in regions of Taiwan where high exposures through drinking water were common  it is not clear whether lower levels of exposure that are common in the United States also are a risk factor for SCC.

52.  Research Question:  Does exposure to inorganic arsenic at lower levels found in the USA increase risk of skin cancer?  Hypothesis  SCC is associated with chronic low-level exposure to arsenic  Null hypothesis  There is NO association between SCC and chronic low-level exposure to arsenic

53. Research Study Design  Case-Control Study of 470 patients with SCC and 447 controls  Appropriate considering rare design and a fairly common exposure.  Exposure assessment:  Urinary arsenic levels (biomarkers representing internal dose)  Well water arsenic level (environmental monitoring representing ambient exposure)  Outcome assessment:  identified incident cases of invasive SCC of the skin that were newly diagnosed in residents 25–74 years of age from July 2003 through June 2009

54. Misclassification  Exposure:  Error in sampling and analysis (non-differential)  Outcome:  Incorrect diagnosis (non-differential)  sex, age, BMI, education, smoking status, skin reaction to chronic sun exposure, and urinary creatinine Confounding

55. Results  In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln- transformed microgram per liter increase in ln- transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80  A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49).

56. Conclusions  Arsenic exposure at low levels is associated with increased odds of SCC  The observed association between methylated forms of As and SCC may reflect the carcinogenicity of those methylated forms or their chemical predecessors

57. Limitations  Limited exposure assessment  One urine sample  Exposure was measured after diagnosis occurred., lack temporality.  SCC treatment could have resulted in changes in As excretion

58. Impact on public health  These findings suggest that common exposure levels may influence cancer risk in the United States and elsewhere.