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American Industrial Hygiene Association Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/aiha20
Inhalation toxicity of hexamethylphosphoramide J. A. ZAPP
a
a
Haskell Laboratory, E. I. du Pont de Nemours & Co., Wilmington, Delaware 19898 Published online: 04 Jun 2010.
To cite this article: J. A. ZAPP (1975) Inhalation toxicity of hexamethylphosphoramide, American Industrial Hygiene Association Journal, 36:12, 916-919, DOI: 10.1080/0002889758507365 To link to this article: http://dx.doi.org/10.1080/0002889758507365
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/ terms-and-conditions
summary reports
...
Inhalation toxicity of hexarnethylphosphoraimide
American Industrial Hygiene Association Journal 1975.36:916-919.
J. A. ZAPP, JR. Haskell Laboratory, E. I. d u Pont de Nemoilrs & Ca, Wilmington, Delaware 19898
Du Pont has informed employees, customers, government agencies and several scientific journals of the following report: Hexamethylphosphoramide, ((CH3)2N)3 P:O, has been receiving increasing use in the last few years as a solvent with exceptional power. Consequently, it is now found in a great many chemical laboratories. The acute toxicity of hexamethylphosphoramide (HMPA) for experimental animals is low to moderate by ingestion, inhalation and skin absorption. It is also a skin irritant. The chronic toxicity of HMPA is, by contrast, more severe. HMPA has been used as an effective chemisterilant for a number of insect pests. It is a chemical mutagen for several insect species and interferes with spermatogenesis in rats. Several investigators have noticed that rats exposed to HMPA by inhalation frequently develop a fatal pneumonia which apparently results from activation of the usually rather benign organisms which are responsible for the endemic chronic murine pneumonitis found in most laboratory rats. With this background, and because of the increasing use of HMPA in the Du Pont Company, we decided to carry out a long-term inhalation toxicity study with rats. Because of previous difficulties in controlling pneumonia among exposed rats in starting the experiment, we used Caesarian-derived rats (Charles River CD Strain), housed them in rooms with laminar flow ventilation and paid strict attention to sanitation. The experiment started in December, 1974, with four groups of 120 male and 120 female rats each, exposed to 0, 50,400, and 4,000 ppb* of HMPA respectively, exposed 6 hours a day, 5 days a week. A planned. 6-month sacrifice of 18 animals from each group showed
compound-related lesions. Between the sixth and the eighth months, a dose-related excess of deaths or sacrifices in extremis occurred in the two highest exposure groups. 'I'he cause of death was predominately degenerative changes in the convoluted tubules of the kidney. ' In August, the eighth month, it was noted that some rats in the two highest exposure groups were developing enlarged noses and were experiencing difficulty in breathing. Sacrifice revealed squamous cell carcinoma which in some cases filled the nasal cavity and penetrated into the brain. The tumors originated from the epithelial lining of the nasal turhinate bones. The incidence was dose-related, 12 nasal tumors being found in 15 rats dead or sacrificed in extremis, out of 240 exposed, in the eighth month in the high exposure group (4,000 ppb) as compared with 7 tumors in 8 dead or sacrificed in extremis, out of 240 e:xposed, in the mid-exposure group (400 ppb). Six rats were randomly selected from the lowclose group (50 ppb) for sacrifice and no malignancy was found. There appears to be no doubt that this rare form of cancer has been produced in rats by inhalation exposure to HMPA in a concentration as low as 400 ppb (analytical) in a period of about eight months. We urge everyone using HMPA to handle it with the precautions appropriate to a plotential carcinogen. Our investigation will continue and will be reported in the scientific literature when completed. 110
*Volumes per 109 volumes
December, 1975
Hexanlethylphosphoric triamide (HM PA)
American Industrial Hygiene Association Journal 1975.36:916-919.
J. WILLIAM LLOYD, SdD. Office of Occupational Health Surveillance and Biorncttrics, National Institute for Occupational Safety and Health, Rockvilk, Maryland 20852
The background material which follows has been prepared by the Office of Occupational Health Surveillance and Biometrics, National Institute for Occupational Safety and Health to alert members of the occupational health community to new information on a potential occupational hazard. The National Institute for Occupational Safety and Health (NIOSH) has received a report from an American producer of hexamethylphosphoric triamide (HMPA), a synthetic organic chemical, indicating that malignant tumors have been produced in laboratory animals by exposure to HMPA. In light of the potential risk of human exposure to1 this chemical in the work environment, the National Institute for Occupational Safety and Health is advising the occupational health community of these findings.
The E. I. du Pont de Nemours and Company (Du Pont) reported to the National Institute for Occupational Safety and Health in a letter dated September 24, 1975, that nasal tumors (squamous cell carcinoma) have been observed in rats exposed to hexamethylphosphoric triamide. NIOSH has also been advised that Du Pont has notified its customers and employees of these findings. Background
HMPA, is a colorless liquid with a density of 1.O3 g/'ml and a boiling point of 232°C. Synonyms for l~examethylphosphorictriamide include: ENT 508 82, hempa, hexametapol, hexamethylphosphamide, hexamethylphosoramide, hexamethylphosphoric acid triamide, hexamc~thy~phosphorotriamide, hexamethylAmerican Industrial Hygiene Association Journal
phosphotriamide, HMPA, HMPT, HPT, phosphoric tris(dimethyamide), phosphoryl hexa.methyltriamide, tris(dimethy1amino)phosphine oxide, and tris(dirnethy1amino)phosphorous oxide. Hexamethylphosphoric triamide is a material possessing unique solvent properties and is widely used as a solvent, in small quantities, in organic and organo-metallic reactions in laboratories.2J This is the major source of occupational exposure to HMPA in the United States. Du Pont, the major manufacturer of hexamethylphosphoric triamide in the United States, periodically produces HMPA at its Chambers Works, Deepwater, New Jersey. Other producers of HMPA in the United States include Chemical Samples Company and Fike Chemical Company. None of Du Pont's HMPA is marketed; all is used internally at its Spruance Plant in Richmond, Virginia, as a processing solvent in the production of Kevlarq' aramid fiber. Du Pont reports that Kevlar contains less than 1 ppm (w/w) of the HMPA which is so firmly held by the fiber that Du Pont believes there is no hazard to customers or employees handling the final fiber product. Hexamethylphosphoric triamide had been manufactured and distributed in the past by Dow Chemical Company (as DORCOL) and Eastman Chemical Products, Inc. (as Inhibitor HPT). Both firms have advised NIOSH that they discontinued these products several years ag0.4: HMPA has been evaluated for use as an ultraviolet light inhibitor in polyvinyl chloride formulations, as an additive for antistatic effects, as a flame retardant, and as a de-icing additive for jet f ~ e l s . ~ - ~ Hexamethylphosphoric triamide has also been extensively investigated as an insect ~hemosterilant.~.~
SUMMARY REPORTS..
.
Toxicity
Pelrmissible occupational exposure
Human:
There is no current Occupational Safety and Health Administration, Department of Labor standard for hexamethylphosphoric triamide exposure.
There are no data available on the toxic effects of hexamethylphosphoric triamide in humans.
American Industrial Hygiene Association Journal 1975.36:916-919.
Animlal:
HMPA is known to have a variety of toxic effects on laboratory animals. Acute toxic effects seen in rats fed HMPA include kidney disease, severe bronchiectasis and bronchopneumonia with squamous metaplasia and fibrosis in lungs.9~10In rabbits, repeated application of HMPA to the skin caused dose related weight loss, altered gastrointestinal function and apparent nervous-system dysfunction.ll Testicular atrophy and aspermia have been observed in rats following oral treatment with HMPA.9J' Oral treatment with HMPA has also been highly inhibitory to testicular development in cockerels.13 HMPA is known to produce mutagenic effects in fruit flies (Drosophila melanogaster).l4 However, studies of the effects of EMPA on humanlj and mice chromosomes16showed no greater frequency of HMPA induced chromosomal aberrations when compared with controls. Preliminary results of an inhalation toxicity study of HMPA, recently released by Du Pont, show nasal tumors in rats exposed daily to 400 and 4,000 parts per billion (ppb) HMPA after 8 months of exposure. In some cases, the tumors originating from the epithelial lining of the nasal turbinate bones filled tho nasal cavity and penetrated into the brain. No nasal tumors were reported among rats exposed to 50 ppb HMPA and controls. Prior to the Du Pont observations, the only other known report of tumors associated with exposure to HMPA was a longterm feeding study by Kimbrough. While lung tumors were observed, the results of this study were inconclusive because the tumor incidence among HMPA exposed rats was not greater than among the control rats.17 Occupational exposure
It is estimated that 5,000 people are occupationally exposed to hexamethylph.osphoric triamide. More than 90 percent of these exposures ase ia research laboratories. *Kevlar is a registered trademark of the Du Pont Company.
918
Procedures and distributors
The following is a list of the major producers and distributors of hexamethylphosphoric triamide: (Source: Personal communications with re~resentativesof chemical manufacturers, Producers
E. I. du Pont de Nemours & Co., Ine. Chemical Samples Company Fike Chemical Colmpany Distri'butors*
Aldrich Chemical Company J. T. Baker Chemical Company Bodman Chemicals Chemical Samples Company Eastrnan Organic Chemicals E. M. Laboratories, Inc. Fike Chemical Company Fisher Scientific Company Guardian Chemical Corporation MCB Manufacturing Chemists Orgmet Peninsular Chemical Research, Inc. Polyscience, h c .
Location
Deepwater, NJ Cleveland, OH Nitro, W V Location
Milwaukee, WS Phillipsburg, NJ Aston Twp., ]PA Columbus, OIH Rochester, NY Elmsforcl, NY Nitro, WV Pittsburgh, PA Hauppauge, 'NY Cincinnati, C)H E. Hampstead, NH Gainesville, :FL Warrington, PA
*Includes domestic and imported HMPA.
December, 1975
American Industrial Hygiene Association Journal 1975.36:916-919.
1. CHEMLXNE, National Library of Medicine, Bethlasda, Maryland, October, 1975 2. FIESIZR, M. and L. F. FIESER:Reagents for Organic Synthesis, John Wiley and Sons, Ltd., New York., 4:244, 1974; 3: 149, 1972; 2:208, 1969; 1:430, 1967. 3. Chemical Abstracts, Clzemical Substances Index. Chemical Abstracts Service, Columbus, Ohio, Vol. 8 1, 1974. 4. Personal communication with representatives of Dow Chemical Company, Midland, Michigan, and :Eastman Chemical Products, Inc., Kingsport, Tennessee. Eastman Technical Data Sheet No. X-203, Eastman Chemical Products, Inc., Kingsport, Tennessee. The Merck Index, 8th Ed., Merck and Company, h c . , Rahway, New Jersey, p, 528, 1968. I . BULL,D. I,. and A. B. ~ o l u t o v ~ Metabolism c: of Carbon-14-Labeled Hempa by Adult Boll Weevils, Rrclt. Etzvirorz. Contam. Toxicol. 1(2):l48 (1973). 8. LANIIA, L.: Action of Chemosterilants in the Reproductive Organs and Tissues of Insects, Proc. Irzt. Cong. Entomol. 13 th, 3:423 (1972). 9. KIMISROUGH, C. D. and T. B. GAXNES: Toxicity of Heximethylphosphoramide in Rats, Nature. 211: 146 ((1966).
NlOSH background information on polychlorinated biphenyls (PCB,~)
American Indusl:rial Hygiene Association Journal
10. KIMBROUGH, C. D. and v. u. SEDLAK: Lung Morphology in Rats Treated with Hexamethylphosphoramide, Toxicol. Appl. Plzartnacol. 12(1):60
(1968). A. B. BORKOVEC and w. A. KNAPP, JR.: Toxicology of Hexamethylphosphoric Triamide in Rats and Rabbits. Toxicol. Appl. Plzarmacol. 17(13):499 (1971). 12. JACKSON, H., A. R. JONES and E. R. A. COOPER: Effects of Hexamethylphosphoramide on Rat Spermatogenesis and Fertility. J . Repro. Feitil. 20:263 (1969). an and C. B. HERRICK: Acute Toxicity 13. SHERMA'N, of Five Insect Chemosierilants, Hemel, Hempa, Tepa, Metepa, and Methotrexate, for Cockerels. Toxicol. Appl. Pharmacol. 16:100 (1970). 14. BEMES,V. and R. J. SRAM:Mutagenic Activity of Some Pesticides in Drosophila Melanogaster. I~zdus.Med. Surg. 38(12):442 (1969). T. H. and w. KLASSEN: Comparative Effects CHANG, of Tretamine, Tepa, Apholate, and Their Structural Analogs on Human Chromosomes in Vitro, Clzronzasorna. 23(3):314 ( 1 968). MANNA, G. K. and P. K. DAS: Effect of two Chemosterilants Apholate and Hempa on the BoneMarrow Chromosomes of Mice. Can. J. Gelzef. Cytol. 15(3):451 (1973). C. D. and T. B. GAINES: The Chronic KIMBROUGH, Toxicity of Hexamethylphosphoramide in Rats. Bull. E I Z V ~ P O Contain. IZ. and Toxicol. 10(4)225 (1973).
1 1. SHOTT,L. D.,
Reports of adverse health effects in humans and the demonstration of carcinogenic effects in cerltain animal species has led to the reexamination of the distribution of polychlorinated biphenyls (PCB's) in the environment and the potential health effects of human exposure. Because the industrial environment represents (the major source of potentially high exposures to PCB's, the National Institute for Occupational Safety and Health (NIOSH) has gathered pertinent information on the rnanufacture, uses and reported deleterious effects of polychlorinated biphenyls and is advising the occupational health community of these hazards. Copies of the full report are available from the Office of Occupational Health Surveillance and Biometrics, National Institute for Occupational Safety and Health, 5600 Fishers Lane, Rockville, Maryland 201852.
American Industrial Hygiene Association Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/aiha20
Inhalation toxicity of hexamethylphosphoramide J. A. ZAPP
a
a
Haskell Laboratory, E. I. du Pont de Nemours & Co., Wilmington, Delaware 19898 Published online: 04 Jun 2010.
To cite this article: J. A. ZAPP (1975) Inhalation toxicity of hexamethylphosphoramide, American Industrial Hygiene Association Journal, 36:12, 916-919, DOI: 10.1080/0002889758507365 To link to this article: http://dx.doi.org/10.1080/0002889758507365
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/ terms-and-conditions
summary reports
...
Inhalation toxicity of hexarnethylphosphoraimide
American Industrial Hygiene Association Journal 1975.36:916-919.
J. A. ZAPP, JR. Haskell Laboratory, E. I. d u Pont de Nemoilrs & Ca, Wilmington, Delaware 19898
Du Pont has informed employees, customers, government agencies and several scientific journals of the following report: Hexamethylphosphoramide, ((CH3)2N)3 P:O, has been receiving increasing use in the last few years as a solvent with exceptional power. Consequently, it is now found in a great many chemical laboratories. The acute toxicity of hexamethylphosphoramide (HMPA) for experimental animals is low to moderate by ingestion, inhalation and skin absorption. It is also a skin irritant. The chronic toxicity of HMPA is, by contrast, more severe. HMPA has been used as an effective chemisterilant for a number of insect pests. It is a chemical mutagen for several insect species and interferes with spermatogenesis in rats. Several investigators have noticed that rats exposed to HMPA by inhalation frequently develop a fatal pneumonia which apparently results from activation of the usually rather benign organisms which are responsible for the endemic chronic murine pneumonitis found in most laboratory rats. With this background, and because of the increasing use of HMPA in the Du Pont Company, we decided to carry out a long-term inhalation toxicity study with rats. Because of previous difficulties in controlling pneumonia among exposed rats in starting the experiment, we used Caesarian-derived rats (Charles River CD Strain), housed them in rooms with laminar flow ventilation and paid strict attention to sanitation. The experiment started in December, 1974, with four groups of 120 male and 120 female rats each, exposed to 0, 50,400, and 4,000 ppb* of HMPA respectively, exposed 6 hours a day, 5 days a week. A planned. 6-month sacrifice of 18 animals from each group showed
compound-related lesions. Between the sixth and the eighth months, a dose-related excess of deaths or sacrifices in extremis occurred in the two highest exposure groups. 'I'he cause of death was predominately degenerative changes in the convoluted tubules of the kidney. ' In August, the eighth month, it was noted that some rats in the two highest exposure groups were developing enlarged noses and were experiencing difficulty in breathing. Sacrifice revealed squamous cell carcinoma which in some cases filled the nasal cavity and penetrated into the brain. The tumors originated from the epithelial lining of the nasal turhinate bones. The incidence was dose-related, 12 nasal tumors being found in 15 rats dead or sacrificed in extremis, out of 240 exposed, in the eighth month in the high exposure group (4,000 ppb) as compared with 7 tumors in 8 dead or sacrificed in extremis, out of 240 e:xposed, in the mid-exposure group (400 ppb). Six rats were randomly selected from the lowclose group (50 ppb) for sacrifice and no malignancy was found. There appears to be no doubt that this rare form of cancer has been produced in rats by inhalation exposure to HMPA in a concentration as low as 400 ppb (analytical) in a period of about eight months. We urge everyone using HMPA to handle it with the precautions appropriate to a plotential carcinogen. Our investigation will continue and will be reported in the scientific literature when completed. 110
*Volumes per 109 volumes
December, 1975
Hexanlethylphosphoric triamide (HM PA)
American Industrial Hygiene Association Journal 1975.36:916-919.
J. WILLIAM LLOYD, SdD. Office of Occupational Health Surveillance and Biorncttrics, National Institute for Occupational Safety and Health, Rockvilk, Maryland 20852
The background material which follows has been prepared by the Office of Occupational Health Surveillance and Biometrics, National Institute for Occupational Safety and Health to alert members of the occupational health community to new information on a potential occupational hazard. The National Institute for Occupational Safety and Health (NIOSH) has received a report from an American producer of hexamethylphosphoric triamide (HMPA), a synthetic organic chemical, indicating that malignant tumors have been produced in laboratory animals by exposure to HMPA. In light of the potential risk of human exposure to1 this chemical in the work environment, the National Institute for Occupational Safety and Health is advising the occupational health community of these findings.
The E. I. du Pont de Nemours and Company (Du Pont) reported to the National Institute for Occupational Safety and Health in a letter dated September 24, 1975, that nasal tumors (squamous cell carcinoma) have been observed in rats exposed to hexamethylphosphoric triamide. NIOSH has also been advised that Du Pont has notified its customers and employees of these findings. Background
HMPA, is a colorless liquid with a density of 1.O3 g/'ml and a boiling point of 232°C. Synonyms for l~examethylphosphorictriamide include: ENT 508 82, hempa, hexametapol, hexamethylphosphamide, hexamethylphosoramide, hexamethylphosphoric acid triamide, hexamc~thy~phosphorotriamide, hexamethylAmerican Industrial Hygiene Association Journal
phosphotriamide, HMPA, HMPT, HPT, phosphoric tris(dimethyamide), phosphoryl hexa.methyltriamide, tris(dimethy1amino)phosphine oxide, and tris(dirnethy1amino)phosphorous oxide. Hexamethylphosphoric triamide is a material possessing unique solvent properties and is widely used as a solvent, in small quantities, in organic and organo-metallic reactions in laboratories.2J This is the major source of occupational exposure to HMPA in the United States. Du Pont, the major manufacturer of hexamethylphosphoric triamide in the United States, periodically produces HMPA at its Chambers Works, Deepwater, New Jersey. Other producers of HMPA in the United States include Chemical Samples Company and Fike Chemical Company. None of Du Pont's HMPA is marketed; all is used internally at its Spruance Plant in Richmond, Virginia, as a processing solvent in the production of Kevlarq' aramid fiber. Du Pont reports that Kevlar contains less than 1 ppm (w/w) of the HMPA which is so firmly held by the fiber that Du Pont believes there is no hazard to customers or employees handling the final fiber product. Hexamethylphosphoric triamide had been manufactured and distributed in the past by Dow Chemical Company (as DORCOL) and Eastman Chemical Products, Inc. (as Inhibitor HPT). Both firms have advised NIOSH that they discontinued these products several years ag0.4: HMPA has been evaluated for use as an ultraviolet light inhibitor in polyvinyl chloride formulations, as an additive for antistatic effects, as a flame retardant, and as a de-icing additive for jet f ~ e l s . ~ - ~ Hexamethylphosphoric triamide has also been extensively investigated as an insect ~hemosterilant.~.~
SUMMARY REPORTS..
.
Toxicity
Pelrmissible occupational exposure
Human:
There is no current Occupational Safety and Health Administration, Department of Labor standard for hexamethylphosphoric triamide exposure.
There are no data available on the toxic effects of hexamethylphosphoric triamide in humans.
American Industrial Hygiene Association Journal 1975.36:916-919.
Animlal:
HMPA is known to have a variety of toxic effects on laboratory animals. Acute toxic effects seen in rats fed HMPA include kidney disease, severe bronchiectasis and bronchopneumonia with squamous metaplasia and fibrosis in lungs.9~10In rabbits, repeated application of HMPA to the skin caused dose related weight loss, altered gastrointestinal function and apparent nervous-system dysfunction.ll Testicular atrophy and aspermia have been observed in rats following oral treatment with HMPA.9J' Oral treatment with HMPA has also been highly inhibitory to testicular development in cockerels.13 HMPA is known to produce mutagenic effects in fruit flies (Drosophila melanogaster).l4 However, studies of the effects of EMPA on humanlj and mice chromosomes16showed no greater frequency of HMPA induced chromosomal aberrations when compared with controls. Preliminary results of an inhalation toxicity study of HMPA, recently released by Du Pont, show nasal tumors in rats exposed daily to 400 and 4,000 parts per billion (ppb) HMPA after 8 months of exposure. In some cases, the tumors originating from the epithelial lining of the nasal turbinate bones filled tho nasal cavity and penetrated into the brain. No nasal tumors were reported among rats exposed to 50 ppb HMPA and controls. Prior to the Du Pont observations, the only other known report of tumors associated with exposure to HMPA was a longterm feeding study by Kimbrough. While lung tumors were observed, the results of this study were inconclusive because the tumor incidence among HMPA exposed rats was not greater than among the control rats.17 Occupational exposure
It is estimated that 5,000 people are occupationally exposed to hexamethylph.osphoric triamide. More than 90 percent of these exposures ase ia research laboratories. *Kevlar is a registered trademark of the Du Pont Company.
918
Procedures and distributors
The following is a list of the major producers and distributors of hexamethylphosphoric triamide: (Source: Personal communications with re~resentativesof chemical manufacturers, Producers
E. I. du Pont de Nemours & Co., Ine. Chemical Samples Company Fike Chemical Colmpany Distri'butors*
Aldrich Chemical Company J. T. Baker Chemical Company Bodman Chemicals Chemical Samples Company Eastrnan Organic Chemicals E. M. Laboratories, Inc. Fike Chemical Company Fisher Scientific Company Guardian Chemical Corporation MCB Manufacturing Chemists Orgmet Peninsular Chemical Research, Inc. Polyscience, h c .
Location
Deepwater, NJ Cleveland, OH Nitro, W V Location
Milwaukee, WS Phillipsburg, NJ Aston Twp., ]PA Columbus, OIH Rochester, NY Elmsforcl, NY Nitro, WV Pittsburgh, PA Hauppauge, 'NY Cincinnati, C)H E. Hampstead, NH Gainesville, :FL Warrington, PA
*Includes domestic and imported HMPA.
December, 1975
American Industrial Hygiene Association Journal 1975.36:916-919.
1. CHEMLXNE, National Library of Medicine, Bethlasda, Maryland, October, 1975 2. FIESIZR, M. and L. F. FIESER:Reagents for Organic Synthesis, John Wiley and Sons, Ltd., New York., 4:244, 1974; 3: 149, 1972; 2:208, 1969; 1:430, 1967. 3. Chemical Abstracts, Clzemical Substances Index. Chemical Abstracts Service, Columbus, Ohio, Vol. 8 1, 1974. 4. Personal communication with representatives of Dow Chemical Company, Midland, Michigan, and :Eastman Chemical Products, Inc., Kingsport, Tennessee. Eastman Technical Data Sheet No. X-203, Eastman Chemical Products, Inc., Kingsport, Tennessee. The Merck Index, 8th Ed., Merck and Company, h c . , Rahway, New Jersey, p, 528, 1968. I . BULL,D. I,. and A. B. ~ o l u t o v ~ Metabolism c: of Carbon-14-Labeled Hempa by Adult Boll Weevils, Rrclt. Etzvirorz. Contam. Toxicol. 1(2):l48 (1973). 8. LANIIA, L.: Action of Chemosterilants in the Reproductive Organs and Tissues of Insects, Proc. Irzt. Cong. Entomol. 13 th, 3:423 (1972). 9. KIMISROUGH, C. D. and T. B. GAXNES: Toxicity of Heximethylphosphoramide in Rats, Nature. 211: 146 ((1966).
NlOSH background information on polychlorinated biphenyls (PCB,~)
American Indusl:rial Hygiene Association Journal
10. KIMBROUGH, C. D. and v. u. SEDLAK: Lung Morphology in Rats Treated with Hexamethylphosphoramide, Toxicol. Appl. Plzartnacol. 12(1):60
(1968). A. B. BORKOVEC and w. A. KNAPP, JR.: Toxicology of Hexamethylphosphoric Triamide in Rats and Rabbits. Toxicol. Appl. Plzarmacol. 17(13):499 (1971). 12. JACKSON, H., A. R. JONES and E. R. A. COOPER: Effects of Hexamethylphosphoramide on Rat Spermatogenesis and Fertility. J . Repro. Feitil. 20:263 (1969). an and C. B. HERRICK: Acute Toxicity 13. SHERMA'N, of Five Insect Chemosierilants, Hemel, Hempa, Tepa, Metepa, and Methotrexate, for Cockerels. Toxicol. Appl. Pharmacol. 16:100 (1970). 14. BEMES,V. and R. J. SRAM:Mutagenic Activity of Some Pesticides in Drosophila Melanogaster. I~zdus.Med. Surg. 38(12):442 (1969). T. H. and w. KLASSEN: Comparative Effects CHANG, of Tretamine, Tepa, Apholate, and Their Structural Analogs on Human Chromosomes in Vitro, Clzronzasorna. 23(3):314 ( 1 968). MANNA, G. K. and P. K. DAS: Effect of two Chemosterilants Apholate and Hempa on the BoneMarrow Chromosomes of Mice. Can. J. Gelzef. Cytol. 15(3):451 (1973). C. D. and T. B. GAINES: The Chronic KIMBROUGH, Toxicity of Hexamethylphosphoramide in Rats. Bull. E I Z V ~ P O Contain. IZ. and Toxicol. 10(4)225 (1973).
1 1. SHOTT,L. D.,
Reports of adverse health effects in humans and the demonstration of carcinogenic effects in cerltain animal species has led to the reexamination of the distribution of polychlorinated biphenyls (PCB's) in the environment and the potential health effects of human exposure. Because the industrial environment represents (the major source of potentially high exposures to PCB's, the National Institute for Occupational Safety and Health (NIOSH) has gathered pertinent information on the rnanufacture, uses and reported deleterious effects of polychlorinated biphenyls and is advising the occupational health community of these hazards. Copies of the full report are available from the Office of Occupational Health Surveillance and Biometrics, National Institute for Occupational Safety and Health, 5600 Fishers Lane, Rockville, Maryland 201852.
