1 Lectures: based on chapter 4 Instructor: Dr. Ephraim Massawe Credit: The Occupational Environment -- Its Evaluation and Control

 Guidelines to control untoward health effects in the traditional workplace  Protection for workers day after day without adverse health effects  Basis for Setting OELs ◦ Human use and experience  Epidemiological data  Medical case histories  Human exposure data vs. adverse effect ◦ Long term animal toxicity studies  Best for chronic toxicity and carcinogenicity ◦ Short term animal toxicity studies  Dermal data on skin penetration  Basis for STEL or Ceiling Limit 2 Credit: The Occupational Environment -- Its Evaluation and Control

 Special studies in animals ◦ Genotoxicity (use of model animals) evaluations pp66  In vitro and In vivo tests are most desirable  Useful for threshold considerations  Limitations – false negatives/false positives? ◦ Developmental/reproductive toxicity studies pp67  Teratogens also included in this category  Male or female reproductive performance?  Behavioral/functions of off-springs or parents? pp67 ◦ Metabolism/pharmacokinetics pp66  Absorption (uptake), distribution, fate and elimination ◦ Physical chemical properties 3 Credit: The Occupational Environment -- Its Evaluation and Control

 Types of exposure & duration pp66 ◦ acute? ◦ Subacute/subchronic-pp66?) ◦ Chronic?  Species tested (rats/dogs/etc…  Chemical factors  Test compounds  Dose, rate, route factors  Route of administration  Genetic factors  Immunologic and dietary factors  Gender, age and emotional status 4 Credit: The Occupational Environment -- Its Evaluation and Control

 Amount required to produce effects  Route of exposure  Type of tumors  Number of species affected  Tumor incidence  Time of tumor  Metabolism  Genetic effects  Other: hormonal status, target organ for non-neoplastic lesions 5 Credit: The Occupational Environment -- Its Evaluation and Control

The projection, extension, or expansion of known data or experience into an area not known or experienced so as to arrive at a usually conjectured knowledge of the unknown area by inferences based on an assumed continuity, correspondence, or other parallelism between it and what is known. (WEBSTER'S Dictionary) 6 Credit: The Occupational Environment -- Its Evaluation and Control

 Established for workday exposure frequencies and duration, not for continuous exposures.  Intended to provide protection for healthy, young, white male workers, not for the general populations.  Based on widely different types and severity of health effects, some of which may be irrelevant for the general population.  Based on data that varies widely in accuracy and age.  Presumed to provide an adequate margin of safety for the workplace, an adjustment difficult to quantify. 7 Credit: The Occupational Environment -- Its Evaluation and Control

 ACGIH TLVs  AIHA WEEL Guides  NIOSH RELs  OSHA PELs Standards-Regulatory  EPA’s____? 8 Credit: The Occupational Environment -- Its Evaluation and Control

Dose = Concentration x Time D = C x T C: You will need to conduct field evaluation to obtain it! T: Time for the task of a worker 9 Credit: The Occupational Environment -- Its Evaluation and Control

 Exposure Dose ◦ That amount of chemical substance to which a given organism is exposed ◦ Expressed as:  parts per million (ppm) for gases & vapors  milligram per cubic meter (mg/m 3 ) for solids i.e. particulates  Absorbed dose: ◦ That amount of a chemical substance deposited in or absorbed by a given organism ◦ Expressed as:  mg/kg 10 Credit: The Occupational Environment -- Its Evaluation and Control

Dose 11 Response Credit: The Occupational Environment -- Its Evaluation and Control

 ACGIH formed in 1939  MAK (Maximum Allowable Concentration) Committee established 1941 pp63 ◦ 5 years later published list of MAKs ◦ Problems with MAK concept  Based on TLVs, not maximum ceiling  Implication of “allowable”  1960 TLVs ® substituted for MAKs  ACGIH Policy  They are not developed for use as legal standards, and the ACGIH does not advocate their use as such (may protect all people in all cases).  The Threshold Limit Values (TLVs ® ) and Biological Exposure Indices (BEIs) are developed as guidelines to assist in the control of health hazards.  These recommendations or guidelines are intended for use in the practice of IH, to be interpreted and applied only by a person trained in this discipline. 12 Credit: The Occupational Environment -- Its Evaluation and Control

“Threshold limit values refer to airborne concentrations of chemical substances and represents conditions under which it is believed that nearly all workers may be repeatedly exposed, day after day, over a working lifetime, without adverse effects.” Susceptible Person “TLVs ® will not adequately protect all persons. Some individuals may experience discomfort or even more serious adverse health effects when exposed to a chemical at the TLV ® or even at concentrations below the TLV ®. There are numerous possible reasons for increased susceptibility to a chemical substance, including age, gender, ethnicity, genetic factors (predisposition), lifestyle choices (e.g., diet, smoking, abuse of alcohol or other drugs), medications, and pre- existing medical conditions (e.g., aggravation of asthma or cardiovascular disease). “ 13 Credit: The Occupational Environment -- Its Evaluation and Control

Air Contaminants  Time-weighted average (TWA)  Ceiling value (C)  Short-term exposure limit (STEL) Range of TLVs Highest ◦ Carbon dioxide ppm Lowest ◦ Strontium chromate mg/cu.m. 14 Credit: The Occupational Environment -- Its Evaluation and Control

 TLVs are established in terms of ppm  mg/m 3 values are determined by calculation conversion based upon 760 mm Hg and 25 o C (77 o F)  If samples are taken at P and T conditions different from TLV NTP conditions and results are in mg and m 3, results must be corrected prior to comparison  Converting Concentration 15 Credit: The Occupational Environment -- Its Evaluation and Control

 TLV Limitations ◦ Not a relative index of toxicity ◦ Not a community allowable limit ◦ Not for exposures >8 hr/day; or >40 hr/wk ◦ Not to be used as proof of hazard (absence of hazard or protective of all people at all times in all cases)  Changes in TLVs ® ◦ Documentation produced ◦ Submitted to committee ◦ Notice of intended change  After January committee meeting 16 Credit: The Occupational Environment -- Its Evaluation and Control

 Sensory irritation e.g. NH 3  Lower respiratory irritation e.g. O 3  Physical irritation e.g. CaCO 3, PNOC  Neuropathic effects e.g. n-Hexane  Metabolic effects e.g. CO, HCN  General systemic toxicity e.g. hexafluoroacetone  Hepatotoxicity e.g. ethylene dichloride  Cancer (carcinogenic) e.g. benzene  Narcosis butane, CFC-12  Sensitization e.g. TDI, MDI  Odor e.g. isopropyl ether  Analogy e.g. aniline derivatives, methemaglobin anaemia  Others e.g. cardiovascular (CS 2 ), ocular (methanol) 428 PELs for which changes were considered by OSHA, 29CFR Part 1910 Air Contaminants; Final Rule 17 Credit: The Occupational Environment -- Its Evaluation and Control

ACGIH Carcinogen  A1Confirmed human carcinogen ◦ human data  A2 Suspected human carcinogen ◦ animal data due to conflicting or insufficient human data  A3 Animal carcinogen ◦ not relevant for extrapolation to humans  A4 Not classified as a human carcinogen ◦ inadequate data  A5 Not suspected as a human carcinogen ◦ good negative human ◦ considers animal data Note: If no data exists, compounds remains unclassified 18 Credit: The Occupational Environment -- Its Evaluation and Control

 Average exposure for an individual over a working period of time as determined by taking one or more samples during the working period 19 TLV - TWA = ——————————— C 1 T 1 + C 2 T 2 + … + C N T N T 1 + T 2 + … + T N Credit: The Occupational Environment -- Its Evaluation and Control

 Average exposure for an individual over an 8-hr working period of time as determined by taking one or more samples during the 8-hr working period 20 Credit: The Occupational Environment -- Its Evaluation and Control A degreaser operator is monitored for exposure to Stoddard solvent. The monitoring data is: Example

Where: C = airborne concentration t = time 21 Eight Hr TLV-TWA = ppm Solution to the Example Credit: The Occupational Environment -- Its Evaluation and Control

 Excursions in worker exposure levels may exceed 3 times the TLV- TWA for no more than a total of 30 minutes during a workday, and under no circumstances should they exceed 5 times the TLV-TWA, provided the TLV-TWA is not exceeded Applicable to TLV-TWAs that do not have STELs 22 Credit: The Occupational Environment -- Its Evaluation and Control Short Term Exposure Limit (STEL) A 15 minute TWA exposure that should not be exceeded anytime during the workday even if 8-hour TWA is within TLV-TWA The concentration to which workers can be exposed continuously for a short period of time without suffering from: irritation chronic or irreversible tissue damage narcosis of sufficient degree to increase the likelihood of accidental injury, impaired self- rescue or materially reduce work efficiency Exposures above TLV-TWA up to STEL: Should not be longer than 15 minutes Should not occur more than 4 times a day Should be at least 60 minutes between successive exposures in this range

 Ceiling Value  Concentration that should not be exceeded during any part of the working exposure  Designated by “C” preceding substance listing  Ceiling Value Determination ◦ In conventional industrial hygiene practice if instantaneous monitoring is not feasible, then the TLV-C can be assessed by sampling over a 15-minute period except for those substances that may cause irritation when exposures are short. 23 Credit: The Occupational Environment -- Its Evaluation and Control

 Substances followed by the designation “Skin” refer to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors, by direct skin contact with the substance.  Air sampling alone may be insufficient to accurately quantify exposure and measures to prevent significant cutaneous absorption may be required. 24 Credit: The Occupational Environment -- Its Evaluation and Control

If the biological effects of mixture components are additive: Where C N = Measured TWA concentration T N = TLV for a substances If ratio is < 1, combined exposure is less than TLV (in compliance) If ratio is > 1, combined exposure exceeds TLV (out of compliance If biological effects of mixture components are:  Synergistic or potentates toxicity; Hazard must be determined individually; and/or Antagonistic No guidelines are presented 25 Credit: The Occupational Environment -- Its Evaluation and Control

Adjustments to the TLVs may be needed to apply the TLVs when work schedules are markedly different from the 8-hour day, 40-hour week. Adjustments are not generally necessary if: ◦ The goal of the exposure limit is to avoid excessive irritation or odor, or ◦ the biological half-life of the toxicant is less than 3 hours or more than 400 hours. 26 Credit: The Occupational Environment -- Its Evaluation and Control

 If the goal of the OEL is to minimize the likelihood of a systemic effect, the concentration to which persons can be exposed should be less than the TLV if: ◦ they work more than 8 hr/day or more than 40 hr/wk, and ◦ the chemical has a half-life between 4 and 400 hours.  If the biological half-life is unknown, a “safe” level can be estimated by assuming that the chemical has a biologic half-life of about 20 hours.  This will generally yield the most conservative adjustment factor for typical 10-, 12-, and 14-hr workdays. 27 Credit: The Occupational Environment -- Its Evaluation and Control

 OSHA Model  Brief and Scala Model ◦ T is the duration of exposure  Hickey and Reist Model t 1 = hours worked per day on unusual schedule t 2 = 24 times days worked/week on unusual schedule 28 Credit: The Occupational Environment -- Its Evaluation and Control

 Assuming that 1,2-trichloroethane has a biologic half-life of 16 hours in people, what modified TLV or PEL would be appropriate for persons who wished to work 3 days, 12 hours per day for the work week.  The present ACGIH TLV and OSHA PEL for 1,2-trichloroethane is 10 ppm.  Solution 29 Credit: The Occupational Environment -- Its Evaluation and Control

Type of LimitRecommending BodyLegally Binding? Permissible exposure limitOccupational Safety and Health Administration Yes Recommended exposure limit National Institute for Occupational Safety and HealthNo Threshold limit valueAmerican Conference of Governmental Industrial Hygienists No Workplace EnvironmentalAmerican Industrial Hygiene Association (AIHA)No Exposure Level New chemical exposure limitEnvironmental Protection Agency (EPA)Yes Maximum allowable Deutsche Forschungsgemeinschaft (Commission for the No concentration Investigation of Health Hazards of Chemical Compounds (translated)in the Work Area) (Germany) Occupational exposure limit Health and Safety Commission &No Health and Safety Executive (Britain) Emergency Response AIHA (community-based standard, not an OEL) No Planning Guide Reference concentration EPA (community-based standard, not an OEL) Yes 30 Credit: The Occupational Environment -- Its Evaluation and Control

LD 50 Probable ToxicityCommonSingle OralVapor ExposureLD 50 Lethal Dose RatingTermDose (Rats)Mortality A Skin (Rabbits) for Humans 1extremely toxic1 mg or less/kg<10 ppm5 mg or less/kga taste, 1 grain 2highly toxic1–50 mg10–1005–43 mg/kg1 teaspoon, 4 cc 3moderately toxic50–500 mg100–100044–340 mg/kg1 ounce, 30 g 4slightly toxic0.5–5 g1000–10, –2.81 g/kg1 pint, 250 g 5practically nontoxic5–15 g10,000–100, –22.59 g/kg1 quart 6relatively harmless15 g and more>100, or more g/kg>1 quart Source: Hodge, H.C. and J.H. Sterner: Tabulation of toxicity classes. Am. Ind. Hyg. Assoc. Q. 10:93 (1949). A Inhalation 4 hours, 2/6–4/6 rats 31 Credit: The Occupational Environment -- Its Evaluation and Control

Hazard Toxicity Categories Indicators I II III IV Oral LD 50 up to and includingfrom 50–500 mg/kgfrom 500–5000 mg/kg>5000 mg/kg 50 mg/kg Inhalation LC 50 up to and includingfrom 0.2–2 mg/Lfrom 2–20 mg/L>20 mg/L 0.2 mg/L Dermal LD 50 up to and includingfrom 200–2000 mg/kgfrom 2000–20,000 mg/kg>20,000 mg/kg 200 mg/kg Eye effectscorrosive; cornealcorneal opacityno corneal opacity;no irritation opacity not reversiblereversible within 7irritation reversible within 7 daysdays; irrigationwithin 7 days persisting for 7 days Skin effectscorrosivesevere irritation at 72 hrsmoderate irritation at 72 hrsmild or slight irritation at 72 hrs Source: Code of Federal Regulations Title 40, Part (h) 32 Credit: The Occupational Environment -- Its Evaluation and Control

Acute oral LD 50 highly toxic; LD 50  50 mg/kgtoxic; 50 mg/kg < LD 50  500 mg/kg Acute dermal LD 50 highly toxic; LD 50  200 mg/kg; 24 hrstoxic; 200 mg/kg < LD 50  1000 mg/kg LC 50 inhalationhighly toxic; LC 50  200 ppmtoxic; 200 ppm; < LC 50  2000 ppm LC 50  2 mg/L; 1 hr2 mg/L  LC 50 < 20 mg/L Carcinogenif IARC “carcinogen” or “potential carcinogen”; or if National Toxicology Program “carcinogen” or “potential carcinogen”; or OSHA regulated carcinogen Corrosivevisible destruction of, or irreversible alterations in living tissue by contact; 4 hrs Irritantnot corrosive; reversible inflammatory effect on living tissue by contact; 4 hrs; skin score  5 Sensitizersubstantial portion of exposed people or animals develop allergic reaction Source: Code of Federal Regulations Title 29, Appendix A 33 Credit: The Occupational Environment -- Its Evaluation and Control

Inhalation Gases,SkinEye AcuteOral A DermalVapors (ppm)IrritationIrritation ToxicityLiquids,Liquids,Dusts, Fumes,Liquids,Liquids, RatingSolidsSolidsMists (mg/L)SolidsSolids LD 50 Rat (mg/kg)LD 50 Rabbit (mg/kg)LC 50 Rat4-hr Exposure B 1-hr Exposure 40–10–200–0.2 mg/Lnot applicablenot applicable 3>1–50>20–200>0.2–2 mg/Lseverelycorrosive; irreversible >20–200 ppmirritating and/orcorneal opacity >20–200 ppmcorrosive 2>50–500>200–1000>2–20 mg/Lprimary irritantirritating or moderately >200–2,000 ppmsensitizerpersisting > 7 days with reversible corneal opacity 34 Credit: The Occupational Environment -- Its Evaluation and Control

Inhalation Gases,SkinEye AcuteOral A DermalVapors (ppm)IrritationIrritation ToxicityLiquids,Liquids,Dusts, Fumes,Liquids,Liquids, RatingSolidsSolidsMists (mg/L)SolidsSolids 1>500–5000>1000–5000>20–200 mg/Lslightly irritatingslightly irritating but >2000–10,000 ppmreversible within 7 days 0>5000>5000>200 mg/Lessentially nonirritatingessentially nonirritating >10,000 ppm A The oral route of exposure is highly unlikely in a workplace setting. If situations are encountered through where the oral LD50 value would indicate a significantly different rating, toxicity values for the other routes of entry may be considered more appropriate when assigning the rating. B Note animal species and duration of exposure if different from that recommended. Source: National Paint & Coatings Association (Hazardous Materials Identification System® HMIS®; Label Master); Washington, DC 35 Credit: The Occupational Environment -- Its Evaluation and Control