Appendix B: Criteria for Chemical Classification
The goal of the CH/EM Plan is to provide a tool which allows the user to quickly and easily design a safe SOP for the use of any chemical found in his/her workplace. When the specific hazards of a chemical are identified and, wherever possible, quantified selection of appropriate controls and workpractices are automatic. In order to use the information presented however, it is vital that the user have a clear understanding of the nature of the information, including its limitations. For this reason, on preparation of the hazard indices and Op MSDSs, clarity and consistency in the use of toxicological and risk terminology are extremely important goals. This section illustrates precisely what information has been utilized and how it has been integrated into the final determination of risk for each of the 12 categories of hazard for which each chemical has been classified.
A. Select Carcinogens
B. Select Teratogens and Reproductive Hazards
C. Highly Toxic Substances
D. Inhalation Hazards
E. Dermal Hazards
F. Corrosive / Serious Irritant
G. Specific Eye Hazard
H. Regulated Chemicals: STEL, Ceiling Values
J. Suspect Carcinogens
K. Suspect Teratogens and Reproductive Hazards
By definition in the Lab Standard (29 CFR 1910.1450 (b)
"Select Carcinogen" means any substance which meets one of the following criteria:
(i) It is regulated by OSHA as a carcinogen;
(ii) It is listed under the category "known to be carcinogens" in the Annual Report on Carcinogens published by the National Toxicology Program (NTP).
(iii) It is listed under Group 1 ("carcinogenic to humans") by the International Agency for Research on Cancer Monographs (IARC).
(iv) It is listed in either Group 2A or 2B by IARC or under the category "reasonably anticipated to be carcinogens" by NTP...and...causes statistically significant tumor incidence in experimental animals in accordance with the following criteria:
(A) After inhalation exposure of 6-7 hours per day, 5 days per week, for a significant portion of a lifetime to dosages of less than 10 mg/m3
(B) After repeated skin application of less than 300 (mg/kg body weight) per week.
(C) After oral dosages of less than 50 mg/kg of body weight per day.
The criteria employed include all OSHA, IARC1A, and NTP 'known' Carcinogens. As some different definitions of dose, species, and endpoint exist, secondary criteria were taken from:
Gold, L.G., Sloane, T.H., and Bernstein, L. Summary of Carcinogenic Potency and Positivity for 492 Rodent Carcinogens in the Carcinogenic Potency Database. (Envrtl. Hlth. Perspect. 79: 259-272 (1989)).
In addition to the reported Rat Oral Doses, results reported for Mouse studies only were scaled by a factor of .58 to approximate equivalent Rat dosages (Davidson, I.W.F., Parker, J.C., Beliles, R.P. Biological Basis for Extrapolation across Mammalian Species. Acad Press 211-238 (1986)).
The criteria for this category are taken from:
- Table 2. Teratogenic Agents in Human Beings, Shepard, T.H., Catalog of Teratogenic Agents, 6th Ed., Johns Hopkins Univ. Press 1988.
- Chemicals with a Reproductive Risk Index 0f 3 or greater (see Classification K for details).
- Any chemical classified as antineoplastic.
Toxic potency is expressed as the dose which produces an effect in a certain percentage of the test population. For acutely toxic effects, this is often the dose in mg/kg body weight which is lethal to half of the population, the LD50 (for oral, topical or injected dosages; by inhalation, the ratio of the concentration of the chemical to air, in parts per million (ppm) is used with the designation LC50). Toxic effects other than lethality may be monitored, for example the initiation of tumours, and given the designation TD50. These values are generally reported for or extrapolated to a standardized population (rats), and are useful for indexing the relative toxicity of chemicals. The actual effect on humans may vary considerably due to differences in metabolism and distribution in the body and mechanisms of detoxification. For some effects, for example reproductive toxicity, the value reported will be the lowest dose at which any individual in the observed group showed an effect, the Tdlo or LDlo . While this number is less statistically reliable, it has the advantage of accommodating some of this uncertainty and more clearly stating the relative risk.
- A chemical that has a median lethal dose (LD50) of 1 milligram or less per kilogram of body weight when administered orally to albino rats weighing between 200 and 300 grams each.
- A chemical that has a median lethal does (LD50) of 5 milligrams or less per kilogram of body weight when administered by continuous contact for 24 hours (or less if death occurs within 24 hours) with the bare skin of albino rabbits weighing between two and three kilograms each.
- A chemical that has a median lethal concentration (LC50) in air of 10 parts per million by volume or less of gas or vapor, or 2 milligrams per liter or less of mist, fume, or dust, when administered by continuous inhalation for one hour (or less if death occurs within one hour) to albino rats weighing between 200 and 300 grams each.
- LD50 50 mg/kg when orally administered as above.
- LD50 200 mg/kg administered by continuous contact as above.
- LD50 200 ppm or 2 mg/L when administered by continuous inhalation as above.
- 50 mg/kg > LD50 500 mg/kg when orally administered as above.
- 200 mg/kg > LD50 1000 mg/kg when administered by continuous contact as above.
- 200 ppm or 2 mg/L > LD50 2000 ppm or 20 mg/L when administered by continuous inhalation as above.
Where available, an equivalent Acute Rat Oral LD50 (the dose level which results in the death of 50% of the test population) is presented.
Substances with an LD50 of 5 mg/kg or less are considered highly toxic.
Substances with an LD50 of 50 mg/kg or less are considered very toxic.
Substances with an LD50 of 500 mg/kg or less are considered toxic.
Substances with an LD50 of 5000 mg/kg or less are considered slightly toxic.
ACUTE TOXICITY OF SOME TYPICAL LABORATORY CHEMICALS
|SUBSTANCE||ACUTE TOXICITY (RAT LD50) mg/kg|
The criteria used to construct Classification "D" include both qualitative and quantitative data. Qualitative information was gathered by selection from the MSDS sheets using the keyword expressions:
"DIFFICULTY IN BREATHING"
"INHALATION MAY BE FATAL"
"MAY BE FATAL IF INHALED"
"HARMFUL BY INHALATION"
"HARMFUL IF INHALED"
INDEX of INHALATION POTENTIAL:
Inhalation Risk Index was computed as the common log of the ratio of vapor pressure to toxicity. The value was then normalized to a scale of 0-5 representing increasing severity.
Recommended Response based on Index:
Index 3 Fume Hood, specifically designed Canopy/Slot Ventilation, or closed reaction vessel required.
Index <3, 2 Above methods MAY be necessary.
Index <2 Normal laboratory ventilation probably adequate
In consideration of specific conditions of use, note the following:
Vapor Pressure is essentially the upper limit equilibrium concentration of a substance in air over a pure solution of the same substance in a closed system. Static conditions of this sort do not occur in 'real life'; the more relevant parameter, Generation Rate, is strongly influenced by:
a. The Temperature, governing molecular activity.
b. The Partition Coefficient for solutions of more than one component.
c. The Surface Area of the liquid/air interface.
d. The Ventilation Rate at the interface.
The effect of temperature on Vapor Pressure may be estimated by assuming a 6% change in VP per degree Centrigrade. Though not a highly precise technique, this can provide valuable information in assessing potential hazard under your conditions of use. Except for extremely toxic substances, chemicals with Vapor Pressures under 5 mm Hg are rarely an inhalation hazard.
Vapor Pressure-derived Indices above are chiefly relevant to pure organic solvents or mixtures of organic solvents with similar physical characteristics:
The Generation Rate of the substance is dependent on its relative concentration in the solution. Low concentration, low risk.
For aqueous solutions, the tendency for the solute to vaporize is balanced by its water solubility. As polarity increases, generation rate rapidly decreases and is virtually nonexistent for many organics and most inorganics. Note this effect particularly for some mineral acids (HF, HCL) which are extremely serious inhalation hazards in the form of pure gasses, but pose no vapor potential as aqueous solutions. The formation of suspended liquid or solid particles in the air - Aerosols -results in a particularly high inhalation risk, and is totally independent of vapor pressure. These particles impact on the inner surface of the lung and provide a nearly 100% effective delivery of dose. Substances without appreciable vapor pressure can become serious inhalation hazards if aerosolized. Be cautious particularly of 'benchtop' centrifuges, and any sonicating device. Be particularly cautious as well when using fine or light dust: the general air motion in our laboratories is sufficient to aerosolize these dusts and maintain relatively stable high ambient air concentrations for extended periods of time.
Although the General Dilution Ventilation Rate in the laboratory is usually quite high -typically 10 Air Changes per hour or more, substances with appreciable vapor pressure and toxicity, or a tendency to aerosolize, and which are generated from a localized source are best handled by Local Exhaust Ventilation - either the Chemical Fume Hood, or well-designed Canopy or Slotted-Duct exhausts. Note particularly in designing work practices that the employee should not be positioned between the source of the contaminant and the face of the exhaust. Note also that the geometry of suction of Local Exhaust Ventilation does NOT resemble a forced 'jet' of air. The efficiency of capture instead falls off as the square of the distance from the face, and may thus be effective only within a few inches, and seldom as much as a foot from the source of generation. Further information regarding the use of the fume hood may be found in Appendix B.
Inhalation Risk Index of some common laboratory chemicals
|SUBSTANCE||INHALATION RISK INDEX|
|1,1-DIMETHYLHYDRAZINE, CARBON DISULFIDE||4.2|
|GLUTARALDEHYDE OSMIUM TETROXIDE||3.9|
|METHANOL, HEXANE (N-)||3.2|
|DIOXANE, MERCRCAPTOETHANOL, ETHANOL||3.1|
|CELLOSOLVE, ANILINE, XYLENE||3.0|
|METHYL SALICYLATE, ACRYLAMIDE||2.5|
Criteria for Dermal Hazards comes chiefly from the Skin Hazard designations defined by OSHA, NIOSH and the ACGIH; and for the values relating dermal penetration to toxic dose as defined by Fiserova-Bergerova, V., Pierce, J.T., Droz, P.O.,(Dermal Absorption Potential of Industrial Chemicals: Criteria for Skin Notation. Am. J. Ind. Med. 17:617-635 (1990)). Currently, only published values are selected.
Qualitative information was gathered by selection from the MSDS sheets using the keyword expressions:
"READILY ABSORBED THROUGH SKIN"
"SENSITIZATION BY SKIN CONTACT"
In addition, data has been abstracted from the bibliographic information presented in Forsberg, K, and Keith, L.H (Chemical Protective Clothing Performance Index Book, John Wiley and Sons, 1989) to characterize specific response of polymer formulations to chemical class. This has been incorporated into a glove selection strategy presented in Appendix C.
Corrosive chemicals are selected from information obtained from the MSDS sheets or RTECs notations, by keyword selection. The keyword employed were:
"SEVERE IRRITATION OR BURNS"
No attempt at quantification was made in defining this list, rather selection was 'conservative' in the direction of inclusion rather than exclusion. "Severe Irritant", by OSHA-defined terminology would not fall into this category, as the definition of "Irritant" excludes those substances capable of producing tissue destruction. However, it was included in our selection criterion to accommodate potential variation in terminology employed by other parties. Similarly, all Organic Acids were automatically included without regard to their ionization potential. In determining the level of protection required, you may wish to consider that corrosivity, and any other toxic property is concentration dependent. Acid solutions with a Ph greater than 2 present little hazard. Greater caution should be exercised in extrapolating hazards of basic substances. The tendency of these substances to solubilize in protein typically leads to greater penetration in intact tissue, with greater tissue destruction occurring over protracted periods of time.
For corrosive substances, tight fitting chemical splash goggles are mandatory, at least when mixing stock solutions. Additional protective clothing may also be required, and a face shield may be advisable. Ordinary rubber gloves of any polymer composition and suitable thickness to withstand abrasion are sufficient for mineral acids and bases, but may not be for organic corrosives.
The criteria for specific eye hazards has been taken from a number of sources, including regulatory designations of OSHA, NIOSH, and the ACGIH, information from MSDS sheets and RTECs notations, and published reviews. In addition, any substance listed under Category "F", "Corrosive" was automatically classified as an Eye Hazard. We have thus far not categorized this information further as to degree of toxicity. For all such substances, subject to the amounts employed and concentration of the contaminant, but not the frequency of use, chemical splash goggles are required.
Qualitative information was gathered by selection from the MSDS sheets using the keyword expressions:
"CAN CAUSE BLINDNESS"
"DAMAGE TO THE EYES"
OSHA has recently revised their listing of maximum permissible breathing zone air concentrations for about 600 substances. These may be found at 29 CFR 1910.1000, summarized there as Tables Z-1 through Z-3. Additional limit values may be found in the Substance Specific Standards (29 CFR 1910.1001 through 29 CFR 1910.1048). These may be found in the EH&S Office. Publication of the Final Rule revising the PELS is in the Federal Register (FR 54 #12 pp 2329-2984, Jan 19, 1989) and this document includes the preamble, which contains the arguments justifying the selected values, and a very valuable summary on the toxicological properties of the regulated substances. In the Laboratory Standard, we are required to maintain air concentrations below these limit values: we are also required to inform our employees of these values, and any additional values proposed by the American Conference of Governmental Industrial Hygienists (ACGIH) or the National Institute for Occupational Safety and Health (NIOSH) for any substances not regulated by OSHA. The PEL-equivalent ACGIH limits are termed the Threshold Limit Values (TLV's), published yearly by that association in the Threshold Limit Value and Biological Exposure Indices. NIOSH limit values are termed the Recommended Limit Values (REL's), are time-weighted over 10 rather than 8 hours, and are summarized in the NIOSH Pocket Guide to Chemical Hazards. As OSHA drew heavily on these sources in revising the PEL's, currently required additions are few in number, so the criterion selected for categories A and B is listing by any of the above sources. In listing specific values for the chemicals in your workplace, preference is given to the OSHA value.
OSHA prioritizes chemicals for regulation based on their toxicity, and usage in the industrial and manufacturing industries. Many of these chemicals are thus commonplace. 8 (and 10) hour time-weighted averages are also designed to afford control in the manufacturing and other process-oriented industries. As much of our use of these chemicals involves brief and intermittent exposure, the PEL's are typically not relevant. If your task analyses indicate 'regular' exposure (see Standard Conditions of Use, Section 2 ) you should contact the EH&S Office for advice on the advisability of additional control procedures, and monitoring. Also, OSHA does not address the potential for synergistic effects of chemicals in its' Standards. The discussion provided in the Preamble to the Laboratory Standard does however indicate a sense of concern, and support for the activities of Associations in providing guidelines. It would be prudent, when considering tasks presenting the possibility of multiple exposures, to adopt the procedures defined by the ACGIH in determining allowable limits. Essentially, these state that for chemicals which affect the same target organ, simultaneous exposures should be considered additive unless there is clear evidence that they are not. Observance of the combined limit value should be determined by summing the ratio of the specific chemical air concentrations to their Limit Values, the combined limit being exceeded when the sum of the ratios exceed 1.
STEL, Ceiling Values.
In the recent revision of the PEL's (effective May 1, 1990), OSHA identified substances for which brief exposures could result in significant pathologies. For 116 such substances, supplemental Short-Term Exposure Limits (STEL's) were defined as the maximum allowable air concentrations to which an individual may be exposed during any 15-minute period. There are in addition Ceiling limit Values, or maximum allowable instantaneous peak concentrations; as instantaneous monitoring is seldom feasible, these are handled as STEL's. Combining the Z-table STEL's and Ceiling Values, similar values in the OSHA Substance-Specific Standards, and the ACGIH and NIOSH recommended values, a total of 172 substances can be defined for which 15 minute time weighted averages are in force.
Semi-quantitative data for this group was obtained from a list generated by Simonsen and Lund, AJIM 21:773-792 (1992). An index of hazard potential was assigned in the range 0 (no risk) to 5 (maximum risk) based on toxicological and physical properties of each substance
VALUES OF SOME TYPICAL LABORATORY CHEMICALS
|SUBSTANCE||NEUROTOXIC RISK INDEX|
Note that many non-polar solvents found in the laboratory possess transient but potent narcotizing effects. Key words employed in recognition of these and other neurotoxic effects are:
"INFLAMMATION OF NERVES"
Criteria for this category include substances from the IARC 2A and 2B and NTP 'Reasonably Anticipated to be Carcinogens' lists for which reported toxicity does not meet the criteria employed in Category "A", or for which insufficient data exists to render judgement. Substances identified as possible Carcinogenic, Tumorigenic or Mutagenic on MSDS sheets or RTECS reports will be included in this category, whether or not quantitative data exists. The selection keyword expressions employed were:
"ALTER GENETIC MATERIAL"
While the requirement for special consideration of defined types of control does not apply to this category, particular attention should be paid to physical properties and task analysis to identify potential routes of exposure. Clear warnings should be posted in potentially contaminated areas, particularly when the area is unattended.
For those chemicals in Category "J" for which a derived Rat Oral TD50 value has been obtained, this information is presented as "Other Known Carcinogens: Relative Chronic Toxicity". Note that these values span a range of 109. Some representative values are presented here to aid you in interpreting your data set:
CHRONIC TOXICITY OF SOME COMMON LABORATORY CHEMICALS
|Substance||Toxicity (TD50) mg/kg|
|PCB's, Ethylene Dibromide||1|
Note that TD50 values above 50 mg/Kg (e.g.., not special carcinogens) are typical for 'environmental' carcinogens. Some substances with TD50 values in the range of 200 mg/Kg have been cleared by the FDA as food additives representing 'de minimis' levels of risk.
Criterion employed in keyword search were:
Cautions employed should be as for Category F., and special consideration given in task analysis to individuals at special risk from exposure to these agents. This category is intended to be inclusive.
Quantitative data for this group was obtained from a list of recommended limit values compiled by Jankovic and Drake, AIHAJ 57:641-649 (1996). An index of hazard potential was developed form the inverse log value of the recommended limit, normalized to the range 0 (very low risk) to 5 (maximum risk).
VALUES OF SOME TYPICAL LABORATORY CHEMICALS
|Substance||Toxicity (TD50) mg/kg|
|PCB's, Ethylene Dibromide||1|
Taken from regulatory listings etc.. Insofar as possible, an attempt has been made to limit this group to substances with demonstrated allergenic potential and to exclude agents which simply promote chemical dermatitis. Specific control procedures are not defined for this diverse group, rather extra attention should be paid to the route and likelihood of exposure, and employees using such substances should consider their history of allergic response.
Keywords employed in the identification of these chemicals include: