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Chapter VI. Procedures for Work with Particularly Hazardous Substances



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Chapter VI. Procedures for Work with Particularly Hazardous Substances




A. Identification and Classification of Particularly Hazardous Substances

As discussed in the previous section (Part VI) of this Laboratory Safety and Chemical Hygiene Plan, hazardous chemicals are chemicals for which there is scientific evidence that adverse acute or chronic health effects may occur in exposed workers. An agent is an acute toxin if its toxic effects are manifested after a single or short-duration exposure. Chronically toxic agents show their effects after repeated or long duration exposure and the effects usually become evident only after a long latency period. There are some substances that pose such significant threats to human health that they are classified as "particularly hazardous substances" (PHSs). The OSHA Laboratory Standard requires that special provisions be established to prevent the harmful exposure of researchers to PHSs. General procedures for working with such materials are presented in detail in Parts VII.C and VII.D below. Three categories of Particularly Hazardous Substances are defined in the OSHA Lab Standard.



1. Select Carcinogens

Certain potent carcinogens are classified as "select carcinogens" and treated as PHSs. A select carcinogen is defined in the OSHA Lab Standard as a substance that meets one of the following

Criteria:
(a) It is regulated by OSHA as a carcinogen,
(b) It is listed as "known to be a carcinogen" in the latest Annual Report on Carcinogens published by the National Toxicology Program (NTP),
(c) It is listed under Group 1 ("carcinogenic to humans") by the International Agency for Research on Cancer (IARC), or
(d) It is listed under IARC Group 2A or 2B, ("probably carcinogenic to humans") or under the category "reasonably anticipated to be a carcinogen" by the NTP, and causes statistically significant tumor incidence in experimental animals in accordance with any of the following criteria: (i) after inhalation exposure of 7 hours per day, 5 days per week, for a significant portion of a lifetime to dosages of less than 10 mg/m3; (ii) after repeated skin application of less than 300 mg/kg of body weight per week; or (iii) after oral dosages of less than 50 mg/kg of body weight per day.
The following Table lists the substances meeting criteria (a), (b), or (c). For information on compounds meeting criteria (d), see copies of the IARC Group 2A and 2B lists and the NTP lists.
Partial List of Select Carcinogens (chemicals in common use in bold)
2-acetylaminofluorene dimethylaminoazobenzene

acrylonitrile ethylene oxide

4-aminobiphenyl ethylenimine

analgesic mixtures containing phenacetin formaldehyde

arsenic and certain arsenic compounds melphalan

asbestos methoxsalen with ultraviolet A therapy

azathioprine methylene chloride (1,1-dichloromethane)

benzene 4,4'-methylene-bis(2-chloroaniline)

benzidine mustard gas

betel quid containing tobacco (chewing) N,N'-bis(2-chloroethyl)-2-naphthylamine

bis(chloromethyl) ether (chlornaphazine)

1,4-butanediol dimethylsulfonate (myleran) -naphthylamine

chlorambucil -naphthylamine

chloromethyl methyl ether 4-nitrobiphenyl

chromium and certain chromium compounds N-nitrosodimethylamine

coal-tar pitches -propiolactone

coal tars shale oils

conjugated estrogens smokeless tobacco products (oral use)

cyclophosphamide soots and soot extracts

1,2 dibromo-3-chloropropane thorium dioxide

3,3'-dichlorobenzidine (and its salts) tobacco smoke

diethylstilbestrol treosulphan

vinyl chloride


2. Reproductive Toxins

Reproductive toxins act during pregnancy and cause adverse effects on the fetus; these effects include embryolethality (death of the fertilized egg, embryo or fetus), malformations (teratogenic effects), and postnatal functional defects. Examples of embryotoxins include thalidomide, and physical agents such as radiation. Women of childbearing potential should note that embryotoxins have the greatest impact during the first trimester of pregnancy. Because a woman often does not know that she is pregnant during this period of high susceptibility, special caution is advised when working with all chemicals, especially those rapidly absorbed through the skin (e.g., formamide, DMSO, etc.). Pregnant women and women intending to become pregnant should consult with their laboratory supervisor and Occupational Health Services before working with substances that are suspected to be reproductive toxins. As minimal precautions, the general procedures outlined in Part VII.C below should be followed for work with such compounds.


The following Table lists some common materials that are highly suspected to be reproductive toxins.
Partial List of Reproductive Toxins (chemicals in common use in bold)
acrylic acid hexachlorobenzene

aniline iodoacetic acid

benzene lead compounds

cadmium mercury compounds



carbon disulfide nitrobenzene

N,N-dimethylacetamide nitrous oxide

dimethylformamide (DMF) phenol

dimethyl sulfoxide (DMSO) polychlorinated and polybrominated

diphenylamine biphenyls

estradiol toluene

formaldehyde vinyl chloride

formamide xylene


The above list is not intended to be complete, and it is the responsibility of researchers (in consultation with their laboratory supervisors) to evaluate each compound involved in their work and to determine whether it should be handled as a reproductive toxin. Women who are pregnant or are planning for pregnancy should review this section regularly.

3. Compounds with a High Degree of Acute Toxicity

Compounds that have a high degree of acute toxicity comprise a third category of particularly hazardous substances as defined by the OSHA Lab Standard. Acutely toxic agents include certain corrosive compounds, irritants, sensitizers (allergens), hepatotoxins, nephrotoxins, neurotoxins, agents that act on the hematopoietic systems, and agents which damage the lungs, skin, eyes, or mucous membranes (see Part VI.B for definitions of these classes of hazardous substances). Substances which have a high degree of acute toxicity are interpreted by OSHA as being substances defined as "toxic" and "highly toxic" agents in 29 CFR 1910.1200 (see Table below and Part XIII), and substances which "may be fatal or cause damage to target organs as the result of a single exposure or exposures of short duration".











Toxic

Highly toxic





Oral LD501


50-500 mg/kg


<50 mg/kg




Skin Contact LD501


200-1000 mg/kg

< 200 mg/kg




Inhalation LD501



200-2000 ppm/air

<200 ppm/air

1albino rats
The following table lists some of the compounds that may be in current use in laboratories at USC and which have a high degree of acute toxicity:
Partial List of Compounds with a High Degree of Acute Toxicity (chemicals in common use in bold)
acrolein hydrogen cyanide

acrylic acid hydrogen fluoride

acrylonitrile hydrogen sulfide

allyl alcohol methyl fluorosulfonate

allylamine methyl iodide

bromine nickel carbonyl

chlorine nicotine

diazomethane nitrogen dioxide

diborane (gas) osmium tetroxide

l,2-dibromoethane ozone

dimethyl sulfate phosgene

ethylene oxide sodium azide



hydrazine sodium cyanide (and other cyanide salts)
The above list is not intended to be complete, and it is the responsibility of the researcher (in consultation with their laboratory supervisor) to evaluate each compound involved in their work and to determine whether it is a substance with a high degree of acute toxicity. Compounds so classified generally must then be handled using the procedures outlined in Part VII.C below. Note, however, that in some circumstances (e.g., when very small quantities of material are being used) it may not be necessary to employ all of the special precautions described in Part VII.C. It is the responsibility of the laboratory supervisor to determine whether a compound with a high degree of acute toxicity is to be treated as a "particularly hazardous substance" in the context of its specific use in his or her laboratory. Finally, several of the compounds listed above require prior approval from the Department Chemical Hygiene Committee before work with them can be carried out. See Part VIII for a discussion of prior approval requirements.
In evaluating the hazards associated with work with toxic substances, it is important to note that a number of factors influence the response of individuals to exposure to a toxic compound. For example, people are rarely exposed to a single biologically active substance. With this point in mind, it is noteworthy that one toxin can influence the effect of a second. Several classic examples are the dramatically enhanced lung carcinogenicity of combined exposure to asbestos and tobacco smoke, and the potentiating activity of phorbol esters on skin carcinogenesis initiated by polycyclic hydrocarbons. There are insufficient data at present to identify which substances potentiate (or possibly even antagonize) the effects of others, but is important for laboratory workers to be cognizant that such interactions can occur. This point underscores the importance of maintaining good laboratory practices at all times, and with all chemicals.
As a final point, it is also noteworthy that the response of an organism to a toxin typically increases with the dose given, but the relationship is not always a linear one. As one example, some carcinogenic alkylating agents show a biphasic dose-mutation curve resembling a hockey stick pointed upward from left to right. It is now well established that the resistance of many organisms to mutagenesis by low doses of simple alkylating agents is due in large measure to a genoprotective system; once that system saturates, at the breakpoint in the curve, the organism becomes much more sensitive to the toxin. This example illustrates two points. First, we have systems that protect against low doses of many toxins (not all, but many). But, as a second, cautionary note, it is pointed out that between individuals there are differences in the levels of genoprotection and other toxin defense systems. These differences are in part genetically determined but also are determined in part by the aggregate exposure of the individual to all chemicals within and outside of the laboratory. Accordingly, it is difficult to estimate exactly how sensitive a given person will be on a given day to a given substance. This point urges once again that a cautious approach be taken in handling all chemicals in the workplace and that appropriate steps be taken at all times to keep exposure to chemicals as low as possible.




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