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INDUSTRIAL HEALTH NEWS
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LITERATURE ABSTRACTS
MEDICAL
ENGINEERING
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CHEMICAL
TOXICOLOGICAL
LEGAL
FEBRUARY, 1967 (Vol. 31, No. 2)
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INDUSTRIAL HYGIENE FOUNDATION
MELLON INSTITUTE
4400 FIFTH AVENUE
PITTSBURGH, PA. 15213
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INDUSTRIAL HYGIENE FOUNDATION OF AMERICA. Inc.
Chemical-Toxicological Series, Bulletin No. 6
RANGK-FINDING TOXICITY DATA FOR 43 COMPOUNDS
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4400 Fifth Avenue Pittsburgh, Pennsylvania
1967
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Copyright, 1967 Industrial Hygiene Foundation of America, Inc.
Pittsburgh, Pa. 'i
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(Printed in U. S. A. )
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FOREWORD
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Individually, the short-term toxicological research findings presented
erein did not merit consideration for publication. Summarized, in tabular
ashion, however, such findings have made useful contribution to the toxico
logical literature.
Sponsors of this research have agreed to collective publication of these j^Jfjndings, and it is hoped that their example will be followed by others in indus-
fy. It is becoming increasingly apparent that such data lying dormant in
dustry's files serves no one.
Undoubtedly, much information which exists will, upon careful study,
be found unsuitable for publication for one reason or another {e. g. , results on
proprietary mixtures of compounds). The Foundation's staff and Chemical-
^j'^ji^xicological Committee are prepared to receive data from individual companies
n order to help develop sufficient data for other similar bulletins in this series
m time to time.
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Steps are also under way to develop better information from human
Q^xjjosure to known concentrations of potentially toxic materials to help validate
?|eshold standards set on data from animal experiments. Much of the human
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will be negative and will never become published, but must be maintained
ina systematic manner nevertheless.
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Extensive cooperation of industry is prerequisite to further progress
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\j is earnestly solicited.
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ACKNOWLEDGMENTS Many persons fiave contributed through their technical performance to the results obtained. In particular, the authors acknowledge the work of Dr. Marion Westrick and Mr. James McNerney. The Research Laboratory is under the direction of Dr. Paul Gross.
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RANGE-FINDING TOXICITY DATA FOR 43 COMPOUNDS* r--"1
William E. Rinehart, Sc.D. , Marianne Kaschak, B. S. and Emil A. Pfitzer, Sc.D.**
Industrial Hygiene Foundation, Pittsburgh, Pennsylvania (o!5\nt roduction:
Range-finding toxicity tests have been performed by the Research Labr---H
Pratory of the Industrial Hygiene Foundation for a number of years. A part of G--J ^jc^hese data have now been made available for publication.
Smyth and Carpenter^1) introduced the range-finding test in the indus-
ial laboratory and have presented data on several hundred materials. (2-6)
Ijheir description of the role of range-finding tests bears repetition here:
. the range-finding test is relied on only to allow predictions of the com
parative hazards of handling new chemicals. Acute toxicity studies, no mat
ter how precisely executed, yield no more than an indication of the degree of
necessary to protect workers or lead to an opinion that certain technically
E|asible applications of a chemical may or may not eventually be proved safe. "
This type of toxicity test procedure is utilized to obtain information
^<C]Qjr precautionary labeling of hazardous household chemicals. Regulations pur}ant to the Federal Hazardous Substances Labeling Act delineate toxicity testing
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^p/jjrjocedures which shall be required for chemicals contained in household sub-
nces. In order to facilitate such toxicity tests the Committee on Toxicology
C^Ophe toxicity data summarized in the report was obtained in part by the followg-ging members of the Foundation: Celanese Corporation, Hoppers Company, Inc.,
Land Pittsburgh Plate Glass Company. P^Vresent address of Dr. Pfitzer: Kettering Laboratory, Cincinnati, Ohio 45219.
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of the National Academy of Sciences-National Research Council has provided a publication titled, "Principles and Procedures for Evaluating the Toxicity of Household Substances.
The purpose of this manuscript is to make available data where none has been previously published, or to allow comparisons where others may have studied the same material.
Methods and Results: The methods for obtaining the range-finding data of this presentation
are generally consistent with the NAS-NRC publication.^ Variations which may be considered important are indicated by appropriate footnotes. Compounds are listed according to their chemical grouping in Table 1.
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See end of table fo r footnotes.
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8.
Discus sion: The toxic doses and irritation scores given in Table 1 for various
materials represent quantitative results on animals from specified test pro cedures. To the person familiar with the procedures, the'doses and scores have approximate meanings in terms of hazard to man. However, in the in terest of providing guidelines to persons unfamiliar with extrapolation of animal data, it was felt worthwhile to make some interpretive comments.
With respect to toxicity, from swallowing, skin penetration and inhala tion, Hodge and Sterner^ have suggested the use of toxicity classes with a
commonly used designation for certain dose ranges and have indicated a probable lethal oral dose for man on the basis of animal data. If data on hu mans indicate a variance, either positively or negatively, such data will, of
course, take precedence. The Hodge and Sterner tabulation of toxicity classes
is given in Table 2.
The Federal Hazardous Substances Labeling Act makes use of a slightly
different grouping of toxic doses. It designates as "highly toxic" those substances
wherein, for half or more than half of a statistically significant group of animals,
the lethal oral dose to rats is 50 mg/kg or less, the lethal dermal penetration
in rabbits is 200 mg/kg or less, and the lethal concentration to rats exposed
for one hour is 200 ppm or less by volume of gas or vapor or 2 mg/1 or less of
mist or dust. Further, it designates as "toxic" those substances with lethal
doses greater than those of the "highly toxic" category but less than 5 gm/kg
for oral doses to rats, less than 2 gm/kg for dermal penetration on rabbits,
and less than 20, 000 ppm by gas or vapor or less than 200 mg/1 of mist or dust
for rats exposed for one hour.
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Table 2 COMBINED TABULATION OF TOXICITY CLASSES*
9.
Various Routes of Administration
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Z)J Commonly Jsed Term
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LDS0 Single Oral**
Dose Rats
Inhalation 4 hr Vapor Exposure
Mortality 2/6-4 /6 Rats
LD50 Skin Rabbits
Probable Lethal Dose
for Man
15 Ixtremely
__toxic
^________
lighly _ toxic
1 mg or less per kg
1 - 50 mg
10 ppm 10-100
5 mg or less per kg
A taste. 1 grain
5-43 mg
1 tsp. 4 cc
Mode rately toxic
50- 500 mg
100-1000
44-340 mg
1 ounce 30 gm
Slightly
2\ toxic
^Practically
"| non-toxic
0. 5-5 g 5-15 g
1000-10,000
.35-2.81 g/kg
1 pint 250 gm
10,000100,000
2. 8222. 59 g/kg
1 quart
cC jelatively
Yz) harmless
1 5 g and more
100,000
22. 6 or more g/kg
y 1 quart
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Os' Hodge, H.C. and Sterner, J. H. American Industrial Hygiene Association
Quarterly, 10:4, 93, Dec. 1943.
lsjCj Standards for intravenous LD^q for rats and rabbits may be obtained approxi
mately by dividing the oral toxicity standards for rats by 10.
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10.
With respect to interpretation of dermal irritation scores, materials
tested by the prescribed techniques of the FHSLA and yielding Draize scores
of 5.0 or greater are designated "primary irritants" and must bear appropriate
labeling if they are considered "household chemicals. " The practice of labeling
industrial chemicals follows the same criterion in general. Draize scores of
less than 5. 0 merely show the relative irritation potential. While not stand
ardized, some toxicologists have utilized an arbitrary procedure wherein a
score of less than 0.5 is insignificant, 0. 5-2.0 represents mild irritation, 2.0
5.0 represents moderate irritation, and greater than 5.0 represents severe
irritation.
A corrosive substance is one that causes visible destruction or irre
versible alterations in the tissue at the site of contact. A substance would be
considered corrosive either by human experience that tissue destruction occurs
or, if when tested on rabbits by the Draize technique discussed above, the ani
mal skin is destroyed or irreversibly changed in 24 hours or less.
The scoring of eye irritation tests is rather complicated and a complete
explanation here might be more confusing than helpful. Perhaps it will be suf
ficient to suggest that any effect on cornea or lens represents an undesirable
condition and average scores of 10/20 or greater for the conjunctivae represent
fairly intense irritation. One must not, however, overlook the importance of
progression of scores with time. While one material may produce an effect
which is rapidly reversible with the eye regaining normal or near normal appear ance within 48 to 72 hours, another material may not recover but may become
worse with time.
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All of the above points, oral toxicity, dermal toxicity, inhalation
r------^jtoxicity, dermal irritation and eye irritation, need to be considered in the assessment of potential hazard from a chemical and the need for caution and/or
.-.-^protective equipment during handling. The likelihood of contact and possible
.--.damage must be postulated in terms of the use (amounts and frequency) and
ltoxic or irritant potential of the substance. Each manufacturer and user of j-C^jhazardous substances must analyze his own process and draw his own con(Occlusions (possibly with the help of qualified industrial hygiene personnel).
References
1.
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Smyth, H. F. , Jr. and Carpenter, C. P. : Plac e of the Range - Finding in the Industrial Toxicology Laboratory, J. Indust. Hyg. & Toxicol. 26: 269, 1 944.
Test
2. Smyth, H. F. , Jr. and Carpenter, C.P. : Further Experience with the Range Finding Test in the Industrial Toxicology Laboratory, J. Indust. Hyg. & Toxicol. 30: 63, 1948.
3. Smyth, H. F. , Jr., Carpenter, C.P., and Weil, C.S. : Range-Finding ' Toxicity Data: List HI, J. Indust. Hyg. & Toxicol. 31: 60, 1949.
_
|\-J4. Smyth, H. F. , Jr., Carpenter, C. P. , and Weil, C. S. : Range-Finding
Toxicity Data: List IV, AMA Arch. Indust. Hyg. & Occ. Med. 4:119, 1951.
5. Smyth, H. F. , Jr., Carpenter, C.P. , Weil, C.S., and Pozzani, U.C.:
<jfn Range-Finding Toxicity Data: List V, AMA Arch. Indust. Hyg. & Occ.
e*
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Med. 10: 61, 1954.
L,------- il- Smyth, H. F. , Jr., Carpenter, C.P. , Weil, C.S., Pozzani, U.C. and
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Striegel, J.A. : Range - Finding Toxicity Data: List VI, Amer. Indust. Hyg. Assoc. J. _2_3: 95, 1962.
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National Academy of Sciences--National Research Council: Principles and Procedures for Evaluating the Toxicity of Household Substances, Publication 1138, Washington, D. C. , 1964.
Hodge, H. C. and Sterner, J. H. : Tabulation of Toxicity Classes, American Industrial Hygiene Association Quarterly, J_0:4, 93, Dec. 1943.
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