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From: tomkaye@galaxy.galstar.com (Tom Kaye)
Newsgroups: alt.drugs
Subject: Inhalant dangers/Info
Date: 5 Mar 1995 22:13:24 GMT
Message-ID: <3jdd25$d1o@mercury.galstar.com>

Newsgroups: alt.drugs
Subject: Re: Inhalant Dangers
Date: 26 Feb 1995 01:01:51 -0500
Additional reading materials


This is posted to help inform those who are curious about the 
dangers of inhalants.

"The Breath of Death"

"Killers of the young"

Tom Kaye RPh.
Tomkaye@galstar.com
Compuserve 76074.207
Phone 918-455- 9450



Research
Publication # 129
National Institutes on Drug Abuse
1992
Charles S. Sharp
Neal Rosenburg M.D.
5600 Fishers lane
Rockville, MD  20857
 
Additional info
Cathy McIntyre
c/o International Institute of Inhalant abuse
fax: 303-788-1860
Phone: 1-800-832-5090
Mention my name Tom Kaye and they will give you full coorporation.

The key points to instil to kids are:
1. Inhalants are different from other drugs.
2. Inhlants rank numer 4 in popularity for use
3. Inhalants cause then most body damage when compared to all the other drugs.
4. Inhalants may kill the first time when used.
5. There are over 1400 inhalant products that kids can use to
   get high.







*****ARCHIVES OF DISEASE IN CHILDHOOD*****


Esmail A  Meyer L  Pottier A  Wright S  
Deaths from volatile substance abuse in those under 18 years: results
  from a national epidemiological study.

In: Arch Dis Child (1993 Sep) 69(3):356-60

The epidemiology of deaths from volatile substance abuse (VSA) in
  those under 18 years that occurred in the UK from 1981-90 is
  described. The analysis of deaths is based on a national register,
  which has information obtained from a regular survey of coroners, the
  Office of Population Censuses and Surveys, and a press clippings
  agency. Altogether 605 people under 18 died from VSA during this
  period. Seventy per cent of deaths occurred between the ages of 14
  and 16. The largest number of deaths were attributed to butane gas
  lighter refills. There was a large north-south gradient in age
  specific mortality ratios (Scotland 180, south east England 87) and
  nearly four times as many deaths occurred in social class V compared
  with social class I. Deaths from VSA are an important and preventable
  cause of deaths in those under 18. Strategies aimed at prevention
  should include measures to reduce experimentation, intervention to
  reduce socioeconomic deprivation, and health education campaigns
  aimed at schools and parents.

Institutional address: 
     Department of Public Health Sciences
     St George's Hospital Medical School
     London.


*****ARCHIVES OF INTERNAL MEDICINE*****


Cartwright TR  Brown ED  Brashear RE  
Pulmonary infiltrates following butane 'fire-breathing'.

In: Arch Intern Med (1983 Oct) 143(10):2007-8

Rapidly progressive bilateral pulmonary infiltrates occurred in a 19-
  year-old man following an unusual hydrocarbon abuse. The acute
  illness was the result of a "trick" known as "fire-breathing." Fire-
  breathing involves filling the oral cavity with butane gas, from an
  ordinary butane cigarette/cigar lighter, and exhalation of the
  volatile vapors over an open flame producing a flame-throwing effect.
  Because of the pulmonary toxic reaction, this activity could have a
  serious or even fatal outcome.


*****BMJ*****

Anderson HR  
Increase in deaths from deliberate inhalation of fuel gases and
  pressurised aerosols [letter]

In: BMJ (1990 Jul 7) 301(6742):41

[No Abstract Available]

(REFERENCE 4 OF 25)
93006467

Esmail A  Anderson HR  Ramsey JD  Taylor J  Pottier A  
Controlling deaths from volatile substance abuse in under 18s: the
  effects of legislation [see comments]

In: BMJ (1992 Sep 19) 305(6855):692
[No Abstract Available]

Institutional address: 
     Department of Public Health Sciences
     St George's Hospital
     Medical School
     London.


*****EMERGENCY MEDICINE CLINICS OF NORTH AMERICA*****
Linden CH  
Volatile substances of abuse.

In: Emerg Med Clin North Am (1990 Aug) 8(3):559-78

Substances that are inhaled for the purpose of recreational self-
  intoxication include aliphatic hydrocarbons, alkyl halides, alkyl
  nitrites, aromatic hydrocarbons, ethers, and ketones. All have the
  ability to cause asphyxia, arrhythmias, cardiovascular depression,
  neurologic dysfunction, and mucosal, pulmonary, and skin irritation
  following acute exposure and permanent neurologic damage with chronic
  exposure. The acute effects of alkyl halides and alkyl nitrites also
  include carbon monoxide poisoning and hepatorenal toxicity, and
  methemoglobinemia, respectively. Chronic exposure to aromatic
  hydrocarbons and ketones can result in liver, kidney, and bone marrow
  injury; myopathy, rhabdomyolysis, metabolic acidosis, and electrolyte
  abnormalities are further complications of chronic aromatic
  hydrocarbon inhalation.

Institutional address: 
     Department of Emergency Medicine
     University of Massachusetts Medical Center
     Worcester.


*****JOURNAL OF THE ROYAL SOCIETY OF MEDICINE*****


D'Costa DF  Gunasekera NP  
Fatal cerebral of edema following trichloroethane abuse.

In: J R Soc Med (1990 Aug) 83(8):533-4

[No Abstract Available]

Institutional address: 
     Department of Medicine
     General Hospital
     Kettering
     Northants.

*****JAMA*****

King GS  Smialek JE  Troutman WG  
Sudden death in adolescents resulting from the inhalation of
  typewriter correction fluid.

In: JAMA (1985 Mar 15) 253(11):1604-6

Inhalation abuse of various toxic agents continues to be a
  significant health problem among the younger segment of our society.
  We describe four cases of sudden death in adolescents associated with
  recreational sniffing of typewriter correction fluid occurring during
  the period 1979 through mid-1984. The solvents used in most of these
  fluids, 1,1,1-trichloroethane and trichloroethylene, are known to
  induce potentially fatal arrhythmias. Sniffing typewriter correction
  fluid poses a significant and underappreciated danger to the lives of
  these abusers. School health officials, public health departments,
  and law enforcement personnel should be alerted to the need for
  surveillance of this type of activity.


*****LANCET*****

(REFERENCE 8 OF 25)
89158540

Gunn J  Wilson J  Mackintosh AF  
Butane sniffing causing ventricular fibrillation [letter]

In: Lancet (1989 Mar 18) 1(8638):617

[No Abstract Available]


*****NEW ENGLAND JOURNAL OF MEDICINE*****

Siegel E  Wason S  
Sudden death caused by inhalation of butane and propane [letter]

In: N Engl J Med (1990 Dec 6) 323(23):1638

[No Abstract Available]

*****SOUTHERN MEDICAL JOURNAL*****

Wegener EE  Barraza KR  Das SK  
Severe frostbite caused by Freon gas.

In: South Med J (1991 Sep) 84(9):1143-6

We have reported a case of severe frostbite due to direct exposure to
  liquid Freon gas (monochlorodifluoromethane), a fluorinated
  hydrocarbon widely used as refrigerants, propellants, and industrial
  solvents. The patient was treated for severe third- and fourth-degree
  frostbite to the hand. The severity of the injury was apparently the
  result of direct through-and-through injury from exposure to the
  liquid (boiling point -40.5 degrees C) and a possible systemic
  vasoconstrictive effect on arterial smooth muscle due to inhalation
  of Freon gas.

Institutional address: 
     Department of Surgery
     University of Mississippi Medical Center
     Jackson 39216-4505.




*****ARUKORU KENKYU-TO YAKUBUTSU ISON JAPANESE JOURNAL OF ALCOHOL STUDIES*****



Tohhara S  Tani N  Nakajima T  Tsuda E  
[Clinical study of butane gas abuse: in comparison with toluene-based
  solvent and marihuana]

In: Arukoru Kenkyuto Yakubutsu Ison (1989 Dec) 24(6):504-10
  (Published in Japanese)

We reported 2 cases of patients who abused butane gas, toluene-based
  solvent and marihuana. They showed different signs in the each
  substance, respectively. Butane gas was easier to make visual
  hallucinations and distorted perception of body form, and was less
  potent and addictive than toluene-based solvent. Spontaneous laughter
  and the most amotivational state were characterized by marihuana
  intoxication. Alteration of auditory perception that simple music
  sounded wonderful was also experienced. Furthermore, the above
  symptoms were thought to change by the order of taking the substance.
  Therefore, it is needed to examine the order of the use of drugs and
  clarify differences of symptoms in abuse among drugs, respectively.

*****BURNS*****


Scerri GV  Regan PJ  Ratcliffe RJ  Roberts AH  
Burns following cigarette lighter fluid abuse.

In: Burns (1992 Aug) 18(4):329-31

Seven patients with burns associated with butane cigarette lighter
  fluid abuse, in a group setting within an enclosed space, are
  presented. In all patients there was a reluctance to admit that
  butane vapour was in use as an intoxicant immediately prior to the
  injury. It is obvious from the circumstances of these injuries that
  the hazardous nature of cigarette lighter fluid is not fully
  appreciated. Since the resultant injuries are usually minor (all
  patients recovered spontaneously with conservative management, the
  hospital stay averaging 2 days), it is probable that many more occur,
  but do not present to accident departments as the victims are wary of
  repercussions should they admit to intoxicant vapour abuse. In view
  of the medical sequelae that can follow butane inhalation, burns unit
  staff should be aware of the problems, their recognition and
  treatment.

Institutional address: 
     Nuffield Burns Units
     Stoke Mandeville Hospital
     Aylesbury
     Buckinghamshire
     UK.


*****CHEMICAL DEPENDENCIES*****

Russe BR  McCoy CB  Barton JE  
Recent findings concerning inhalant use.

In: Chem Depend (1980) 4(1-2):113-26

[No Abstract Available]


*****HUMAN TOXICOLOGY*****


Marjot R  McLeod AA  
Chronic non-neurological toxicity from volatile substance abuse.

In: Hum Toxicol (1989 Jul) 8(4):301-6

1. Most of the evidence for chronic non-neurological toxicity from
  volatile substance abuse is derived from case reports. 2. Factors
  important in assessing these reports are the marked variations in
  exposure conditions and in the composition of the products abused. 3.
  In a young and otherwise healthy population, any chronic organ
  toxicity arising from VSA has to be gross in order to become
  clinically apparent. This may partially explain the relatively low
  incidence of reporting. 4. Toluene and the chlorinated hydrocarbons
  1,1,1-trichloroethane and trichloroethylene can cause permanent
  damage to the kidney, liver, heart and lung, in certain volatile
  substance abusers.

Institutional address: 
     Department of Anaesthetics
     Kings College Hospital
     Denmark Hill
     London
     UK.


Ramsey J  Anderson HR  Bloor K  Flanagan RJ  
An introduction to the practice, prevalence and chemical toxicology
  of volatile substance abuse.

In: Hum Toxicol (1989 Jul) 8(4):261-9

1. Volatile substance abuse is largely a teenage practice; it is
  estimated that in the UK 3.5-10% of young people have at least
  experimented and that 0.5-1% are current users. 2. The products
  abused are many and varied but only about 20 chemical compounds,
  notably toluene, chlorinated solvents such as 1,1,1-trichloroethane,
  fuel gases such as butane and aerosol propellants, are commonly
  encountered. 3. The acute hazard varies with the compound, product
  and mode of abuse. Mortality in the UK is now about 100 per year,
  from all social classes, 90% of whom are male. 4. Chronic toxicity is
  difficult to assess, partly because of the diversity of products
  abused. However it is clear that some long-term abusers suffer
  permanent damage to the central nervous system, heart, liver and
  kidney. 5. Toxicological analysis may be relied upon for confirmation
  of diagnosis, providing attention is paid to the kinetics of
  excretion and stability in the sample. 6. Responses include codes of
  practice for the sale of products and educational strategies;
  legislation has also been enacted. There is little evidence that any
  of these measures have made a significant impact on the problem.

Institutional address: 
     Chemical Pathology Laboratory
     St George's Hospital Medical School
     Cranmer Terrace
     London
     UK.


*****JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION*****


*****JOURNAL OF OCCUPATIONAL MEDICINE*****

Tauber JB  
Instant benzol death.

In: J Occup Med (1970 Dec) 12(12):520-3

[No Abstract Available]


*****PSYCHIATRIC CLINICS OF NORTH AMERICA*****


Cohen S  
The hallucinogens and the inhalants.

In: Psychiatr Clin North Am (1984 Dec) 7(4):681-8

The hallucinogenic drugs represent a recurrent outbreak pattern with
  each generation or two seeming to rediscover their ego-dissolving
  effects. The inhalants produce a short-lived intoxication with
  certain volatile solvents affecting specific organ systems.


*****TOXICOLOGY AND APPLIED PHARMACOLOGY*****


Bruckner JV  Peterson RG  
Evaluation of toluene and acetone inhalant abuse. II. Model
  development and toxicology.

In: Toxicol Appl Pharmacol (1981 Dec) 61(3):302-12


                Center for Substance Abuse Prevention
    Substance Abuse and Mental Health Services Administration
                     U. S. Public Health Service
            U. S. Department of Health and Human Services
                              ---------
          for more information or assistance, contact ....

    The National Clearinghouse for Alcohol and Drug Information
                            P.O. Box 2345
                      Rockville, Maryland 20847
                            1-800-729-6686



                     National High School Senior Survey
                     ----------------------------------

                          PERCENT WHO EVER USED

CLASS OF                1982  1983  1984  1985  1986  1987  1988  1989  1990

Marijuana/Hashish       58.7  57.0  54.9  54.2  50.9  50.2  47.2  43.7  40.7
----------------------------------------------------------------------------
Inhalants               12.8  13.6  14.4  15.4  15.9  17.0  16.7  17.6  18.0
Inhalants Adjusted*     17.7  18.2  18.0  18.1  20.1  18.6  17.5  18.6  18.5
  Amyl/Butyl Nitrites    9.8   8.4   8.1   7.9   8.6   4.7   3.2   3.3   2.1
----------------------------------------------------------------------------
Hallicinogens           12.5  11.9  10.7  10.3   9.7  10.3   8.9   9.4   9.4
Hallicinogens Adj**     14.3  13.6  12.3  12.1  11.9  10.6   9.2   9.9   9.7
  LSD                    9.6   8.9   8.0   7.5   7.2   8.4   7.7   8.3   8.7
  PCP                    6.0   5.6   5.0   4.9   4.8   3.0   2.9   3.9   2.8
----------------------------------------------------------------------------
*Inhalants ajusted for underreporting of amyl and butyl nitrites.
**Hallucinogens adjusted for underreporting of PCP.



                          PERCENT WHO EVER USED
CLASS OF                1982  1983  1984  1985  1986  1987  1988  1989  1990

Cocaine                 16.0  16.2  16.1  17.3  16.9  15.2  12.1  10.3   9.4
  Crack                  NA    NA    NA    NA    NA    4.6   4.8   4.7   3.5
  Other Cocaine          NA    NA    NA    NA    NA   14.0  12.1   8.5   8.6
----------------------------------------------------------------------------
Heroin                   1.2   1.2   1.3   1.2   1.1   1.2   1.1   1.3   1.3
  Other Opiates          9.6   9.4   9.7  10.2   9.0   9.2   8.6   8.3   8.3
----------------------------------------------------------------------------
Stimulants              35.6  35.4   NA    NA    NA    NA    NA    NA    NA
  Stimulants Adj*       27.9  26.9  27.9  26.2  23.4  21.6  19.8  19.1  17.5
----------------------------------------------------------------------------
Sedatives               15.2  14.4  13.3  11.8  10.4   8.7   7.8   7.4   5.3
  Barbiturates          10.3   9.9   9.9   9.2   8.4   7.4   6.7   6.5   6.8
  Methaqualone          10.7  10.1   8.3   6.7   5.2   4.0   3.3   2.7   2.3
----------------------------------------------------------------------------
Tranquilizers           14.0  13.3  12.4  11.9  10.9  10.9   9.4   7.6   7.2
----------------------------------------------------------------------------
*Stimulants adjusted to exclude inappropriate reporting of
nonprescription stimulants.



                           PERCENT WHO EVER USED 
CLASS OF                1982  1983  1984  1985  1986  1987  1988  1989  1990

Alcohol                 92.8  92.6  92.6  92.2  91.3  92.2  92.0  90.7  89.5
----------------------------------------------------------------------------
Cigarettes              70.1  70.6  69.7  68.8  67.6  67.2  66.4  65.7  64.4
----------------------------------------------------------------------------
Term "Ever Used" refers to use of substance at least one time.

This information was supplied by the U.S. Depratment of Health
and Human Services, Public Health Service, Alcohol, Drug Abuse,
and Mental Health Administration.  Revised January, 1991.

These numbers were gathered in annual nationwide surveys
conducted for the National Institute of Drug Abuse by the
University of Michigan Institute for Social Reseach.  The 1990
survey involved more than 15,000 seniors from public and private
schools.

The above data refer to use not under a doctor's orders.


*****AMERICAN JOURNAL OF MEDICINE*****


Haverkos HW  Dougherty J  
Health hazards of nitrite inhalants.

In: Am J Med (1988 Mar) 84(3 Pt 1):479-82

[No Abstract Available]

Institutional address: 
     Clinical Medicine Branch
     National Institute on Drug Abuse
     Rockville
     Maryland 20857.


*****BIOCHEMISTRY*****


Gadella TW Jr  Moritz A  Westerman J  Wirtz KW  
Enzymatic synthesis of pyrene-labeled polyphosphoinositides and their
  behavior in organic solvents and phosphatidylcholine bilayers.

In: Biochemistry (1990 Apr 3) 29(13):3389-95

A method is reported for the synthesis of pyrene-labeled analogues of
  phosphatidylinositol 4-phosphate (Pyr-PIP) and phosphatidylinositol
  4,5-biphosphate (Pyr-PIP2) from sn-2-(pyrenyl-
  decanoyl)phosphatidylinositol (Pyr-PI) using partially purified PI
  and PIP kinase preparations. Phosphorylation of Pyr-PI and Pyr-PIP
  was extensive (more than 50%) provided that the ATP concentration was
  high and that stabilizing agents such as sucrose and polyethylene
  glycol were present in the incubation medium. Pyr-PIP and Pyr-PIP2
  were isolated by chromatography on immobilized neomycin. The identity
  of the products was established by thin-layer chromatography, UV-
  absorption spectroscopy, and spectrofluorometry. The pyrene
  excimer/monomer fluorescence technique revealed that, in contrast to
  Pyr-PI, Pyr-PIP and Pyr-PIP2 formed clusters in organic solvents. By
  use of the same technique for model membranes, it was shown that in
  phosphatidylcholine bilayers the collision frequency of the three
  fluorescent phosphoinositides decreased in the order PI greater than
  PIP greater than PIP2. Addition of Ca2+ at concentrations above 0.1
  mM increased the collision frequency of Pyr-PIP2 and, to a much
  lesser extent, Pyr-PIP; Ca2+ had no effect on Pyr-PI.

Institutional address: 
     Centre for Biomembranes and Lipid Enzymology
     State University of Utrecht
     The Netherlands.


*****CANCER RESEARCH*****


Armstrong RW  Armstrong MJ  Yu MC  Henderson BE  
Salted fish and inhalants as risk factors for nasopharyngeal
  carcinoma in Malaysian Chinese.

In: Cancer Res (1983 Jun) 43(6):2967-70

We conducted a case-control study of nasopharyngeal carcinoma among
  Malaysian Chinese to test inhalants, salted fish consumption, and use
  of tobacco, alcohol, and nasal ointments as risk factors for the
  disease. Interviews with 100 cases and 100 controls indicated that
  salted fish consumption during childhood was a significant risk
  factor (relative risk, 3.0; p = 0.04); childhood daily consumption of
  this food item compared to nonconsumption carried a relative risk of
  17.4 [95% confidence interval = (2.7, 111.1)]. Occupational exposure
  to smokes (relative risk, 6.0; p = 0.006) and to dusts (relative
  risk, 4.0; p less than 0.001) was also significantly associated with
  nasopharyngeal carcinoma. The two risk factors (consumption of salted
  fish and exposure to smoke and/or dust) were independent of each
  other. There was no association between nasopharyngeal carcinoma and
  tobacco, alcohol, or nasal ointments.

Institutional address: 
     School of Public Health
     University of Hawaii
     Honolulu.


*****JOURNAL OF BIOLOGICAL CHEMISTRY*****


Wallis KT  Azhar S  Rho MB  Lewis SA  Cowan NJ  Murphy DB  
The mechanism of equilibrium binding of microtubule-associated
  protein 2 to microtubules. Binding is a multi-phasic process and
  exhibits positive cooperativity.

In: J Biol Chem (1993 Jul 15) 268(20):15158-67

The mechanism of binding of microtubule-associated protein 2 (MAP2)
  to taxol-stabilized microtubules (MTs) was examined through Scatchard
  analysis of equilibrium binding and by immunoelectron microscopy. We
  demonstrate the following. 1) Binding is a cooperative process as
  indicated by sigmoidal binding curves, prominent humps in Scatchard
  plots, and an all-or-none response in binding during ligand
  titrations. At high tubulin/MAP2 ratios, the Kd for noncontiguous
  binding (5-25 microM) is estimated to be 100-1500 times greater than
  that predicted for contiguous binding, suggesting a high degree of
  cooperativity. 2) Cooperativity is indicated independently by a
  highly clustered or patchy distribution of MAP2 on MTs as revealed by
  immunoelectron microscopy. 3) The binding of truncated constructs of
  mouse MAP2 protein suggests that a domain of MAP2 conferring
  cooperativity is located in or near the MT binding site near the
  carboxyl terminus. We speculate that in the cell, cooperativity may
  generate MTs with uniform biochemical properties and contribute to
  the segregation of MAPs in neuronal cell processes.

Institutional address: 
     Department of Cell Biology and Anatomy
     Johns Hopkins University School of Medicine
     Baltimore
     Maryland 21205.


*****JOURNAL OF NEUROSURGERY*****


Spigelman MK  Zappulla RA  Johnson J  Goldsmith SJ  Malis LI  
  Holland JF  
Etoposide-induced blood-brain barrier disruption. Effect of drug
  compared with that of solvents.

In: J Neurosurg (1984 Oct) 61(4):674-8

The intracarotid infusion of the anti-neoplastic compound, etoposide,
  has been shown to exert a dose-dependent effect on blood-brain
  barrier (BBB) permeability. Etoposide, however, is formulated in a
  complex solvent solution containing alcohol, Tween 80, polyethylene
  glycol 300, and citric acid. To investigate the contribution of the
  solvent solution to BBB disruption, the authors studied Sprague-
  Dawley rats after the internal carotid artery infusion of the solvent
  solution with and without the addition of etoposide. Experiments were
  performed at four doses of drug and/or solvent. Disruption of the BBB
  was evaluated qualitatively by the appearance of the systemically
  administered dye, Evans blue, in the cerebral hemispheres and
  quantitatively by the ratio of gamma counts of the technetium-labeled
  chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the
  ipsilateral:contralateral hemisphere. Significant barrier opening was
  obtained in all four groups of animals infused with solvent plus
  etoposide. In the corresponding groups of rats infused with the
  solvent solution alone, BBB disruption was markedly lower. Only in
  the group infused with the largest dose of solvent was the
  hemispheric ratio of 99mTc-DTPA significantly different from saline-
  infused animals. Each of the groups with solvent plus etoposide had
  99mTc-DTPA ratios significantly different from the control group.
  Intracarotid infusion and subsequent BBB disruption were well
  tolerated by the animals receiving either solvent alone or solvent
  and etoposide. Disruption of the BBB secondary to the intracarotid
  infusion of etoposide is primarily caused by the drug itself and not
  by the solvent solution.

Institutional address: 
     Department of Neoplastic Diseases
     Mount Sinai School of Medicine
     New York
     New York.




*****ADVANCES IN BIOCHEMICAL PSYCHOPHARMACOLOGY*****

(REFERENCE 6 OF 22)
88291911

Haverkos HW  
Kaposi's sarcoma and nitrite inhalants.

In: Adv Biochem Psychopharmacol (1988) 44:165-72

[No Abstract Available]

Institutional address: 
     Clinical Medicine Branch
     National Institute on Drug Abuse
     Alcohol
     Drug Abuse
     Rockville
     Maryland 20857.


*****AKAD WISS*****


Horn KH  
[LIMITS AND POSSIBILITIES OF ANIMAL EXPERIMENTS WITH CARCINOGENIC
  INHALANTS]

In: Akad Wiss (1978)(2):52-62  (Published in German)

Animal inhalation studies with chemical carcinogens or cocarcinogens
  are reviewed and their relevance to cancer induction in humans is
  discussed. Current inhalation techniques are not completely reliable
  due to the short life span of the test animals (eg, rats and Syrian
  golden hamsters) and the long observation periods needed to
  approximate human exposures. With the development of more
  sophisticated inhalation equipment, more positive results may be
  obtained with definite carcinogens. Another difficulty with the
  inhalation method is the evaluation of a positive result; ie, whether
  a substance such as ferric trioxide is carcinogenic, cocarcinogenic,
  or causes cytopathological conditions that promote development.
  Intratracheal intubation and implantation techniques are more
  accurate in the production of respiratory tract tumors, and they are
  useful in screening possible carcinogenic inhalants. The system
  application method is adequate only when testing a known carcinogen
  whose activity (po or sc) is organ-specific in the test species.
  However, this technique is useful in that the exact dose can be
  applied and the synergistic and/or cocarcinogenic properties of the
  test substance can be ascertained. To relate respiratory tract
  carcinogenesis in man to animal experiments will require the
  perfection of application techniques and the identification of more
  suitable animal models. (61 Refs)

Institutional address: 
     No affiliation given



*****AMERICAN JOURNAL OF INDUSTRIAL MEDICINE*****


Park RM  Silverstein MA  Green MA  Mirer FE  
Brain cancer mortality at a manufacturer of aerospace
  electromechanical systems.

In: Am J Ind Med (1990) 17(5):537-52

Standardized proportional mortality ratios and mortality odds ratios
  were calculated for 583 deaths between 1950 and 1986 among employees
  who had worked for at least 10 years at a facility manufacturing
  missile and aircraft guidance systems. There was a statistically
  significant excess of brain cancer proportional mortality (PMR =
  16/3.8 = 4.2, p = .0001). Among hourly employees, 12 brain cancer
  deaths occurred for 2.7 expected (PMR = 4.4, p = .00005). The PMR for
  brain cancer increased from 1.8 (p = .45) among hourly workers with
  less than 20 years to 8.7 (p = .000003) in those with more than 20
  years employment. Work in "clean rooms," where gyroscopes were
  assembled, was associated with the brain cancer excess but did not
  fully account for it. Among 105 deceased hourly women, all three
  brain cancer deaths occurred among gyro assemblers working in clean
  rooms, and the risk increased with duration in clean rooms. Although
  the proportion of brain cancer deaths among hourly men with clean-
  room experience was similar to that for women, only three of the
  seven male brain cancer deaths occurred in this group. The suspect
  agents include gyro fluids and chlorofluorocarbon solvents.

Institutional address: 
     Health and Safety Department
     United Auto Workers International Union
     Detroit
     MI 48214.


*****ANNALS OF THE NEW YORK ACADEMY OF SCIENCES*****


Zimmerman HM  
PRODUCTION OF BRAIN TUMORS WITH AROMATIC HYDROCARBONS

In: Ann N Y Acad Sci (1982) 381:320-324

This contribution constitutes a summary review of 40 years of work in
  the experimental production of gliomas in mice with the chemical
  carcinogens 20-methylcholanthrene, benzpyrene, and 1,2,5,6-
  dibenzanthracene, all three aromatic hydrocarbons. Frequent notation
  is made of the pertinence of the experimental results to the glioma
  problems in man. (Author abstract) (17 Refs)

Institutional address: 
     Montefiore Hosp. and Medical Center
     111 East 210th St.
     Bronx
     NY
     10467


*****ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY*****

(
Dahl AR  Lewis JL  
Respiratory tract uptake of inhalants and metabolism of xenobiotics.

In: Annu Rev Pharmacol Toxicol (1993) 33:383-407

The combined impact of new research regarding the dosimetry of
  inhalants, discussed in early paragraphs of this review, and the
  rapidly developing knowledge regarding the location and substrate
  specificities of the enzymes responsible for xenobiotic metabolism
  should soon lead to new insights into the causes and prevention of
  cancer and other diseases of the respiratory tract and may provide
  insight into the design of drugs used in the treatment of respiratory
  tract disease. Among the developments to be expected within the next
  decade are the following: 1. The issue of extrapulmonary versus
  intrapulmonary activation of lung prodrugs and protoxicants will be
  resolved by validation of the different dosimetries predicted for
  highly lipophilic inhalants compared to less lipophilic ones. 2. The
  possibly complex roles of P450 isozymes 1A1 and 2D6 and other forms
  in the causation of human lung cancer will undoubtedly be better
  understood in the next few years. 3. Interspecies comparisons of
  respiratory tract enzyme activities--both activating and detoxicating-
  -will lead to improved use of laboratory animals as models for
  expected toxicological and pharmacological effects in humans. 4. The
  potential role of nasal uptake and metabolism in causing brain
  disease will be established or denied experimentally. 5. The complex
  relationships between host factors--such as hormone levels and the
  presence of inflammation--and metabolism-mediated toxicity will
  become clearer. 6. As new research results continue to illuminate the
  complexities of the interactions of xenobiotics with respiratory
  tract tissue, clues as to how best to administer drugs via the
  respiratory tract and understanding of changes in disease patterns--
  such as the recent shift in sites for lung cancer--will follow.

Institutional address: 
     Inhalation Toxicology Research Institute
     Albuquerque
     New Mexico 87185.


*****BIOCHEMICAL PHARMACOLOGY*****



Juorio AV  Yu PH  
Effects of benzene and other organic solvents on the decarboxylation
  of some brain aromatic-L-amino acids.

In: Biochem Pharmacol (1985 May 1) 34(9):1381-7

The intraperitoneal administration of benzene produced marked
  increases in mouse striatal concentrations of beta-phenylethylamine,
  p-tyramine and, to a lesser extent, m-tyramine. Similar increases
  were observed in rat striatal p- and m-tyramine. The subcutaneous
  administration of benzene dissolved in sesame oil increased mouse
  striatal p-tyramine but did not change m-tyramine. Benzene
  administration to mice pretreated with p-tyrosine produced marked
  increases in mouse striatal p-tyramine as well as in m-tyramine. The
  statistical analysis of the results indicated that the treatment
  produced an interaction that led to an increase in the concentration
  of both the p- and m-isomers of tyramine. The administration of
  benzene to m-tyrosine-pretreated mice increased striatal m-tyramine
  but p-tyramine was not increased. The treatment produced no
  potentiation in the formation of p- or m-tyramine. Of the other
  organic solvents given, pyridine produced the most marked effects.
  Its administration increased the concentration of both p- and m-
  tyramine in the mouse striatum. Treatment with toluene, chloroform,
  carbon tetrachloride or isoamylalcohol produced moderate increases in
  mouse striatal p-tyramine while toluene, dichloromethane or
  isobutylalcohol also increased m-tyramine. These increases in brain
  beta-phenylethylamine, p-tyramine and m-tyramine may play a
  contributory role in the human toxicity of benzene and some of these
  organic solvents; these toxic effects could be exacerbated after
  ingestion of foodstuffs containing the aminoacids phenylalanine or p-
  tyrosine or for those under treatment with a monoamine oxidase
  inhibitor.

Institutional address: 
     Psychiatric Research Division
     Saskatchewan Health
     Saskatoon
     Canada.


*****CARCINOGENESIS*****


Moser GJ  Smart RC  
Hepatic tumor-promoting chlorinated hydrocarbons stimulate protein
  kinase C activity.

In: Carcinogenesis (1989 May) 10(5):851-6

Various chlorinated hydrocarbons, many of which are known hepatic
  tumor promoters, have been evaluated for their ability to stimulate
  protein kinase C (PKC) activity in vitro. Chlordane, kepone,
  toxaphene, heptachlor, 2,2-bis(4-chlorophenyl)-1,1-dichloroethane,
  the polychlorinated biphenyl Aroclor 1254, aldrin, 2,2-bis(4-
  chlorophenyl)-1,1,1-trichloroethane (DDT) and gamma-
  hexachlorocyclohexane (lindane) were the most potent stimulators of
  PKC activity. Of these compounds, chlordane was the most potent
  organochlorine pesticide. Chlordane (100 microM) stimulated mouse
  brain PKC activity in the 10(5) g supernatant to a maximum velocity
  equal to that obtained when the enzyme was maximally stimulated with
  the skin-tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-
  acetate (TPA). Chlordane concentrations as low as 1 microM
  significantly stimulated PKC activity. Chlordane-stimulated PKC
  activity was calcium-dependent, and in the presence of exogenous
  calcium, chlordane-stimulated PKC activity was at least 5-fold
  greater than in the absence of added calcium. In contrast, the
  addition of calcium only minimally affected (less than 30% increase)
  the TPA-stimulated PKC activity. Concentrations of TPA and chlordane
  which maximally stimulate PKC did not produce an additive effect on
  PKC activity. Chlordane- and TPA- stimulated PKC activity was
  phospholipid-dependent and could be inhibited by quercetin, a known
  inhibitor of PKC activity. Chlordane in the presence of calcium also
  stimulated mouse epidermal and hepatic PKC as well as purified rat
  brain PKC. These results demonstrate that a wide variety of
  chlorinated hydrocarbons, which are considered hepatic tumor
  promoters, stimulate protein kinase C activity in vitro.

Institutional address: 
     Toxicology Program
     North Carolina State University
     Raleigh 27695-7633.


*****CRITICAL REVIEWS IN TOXICOLOGY*****



Dahl AR  Hadley WM  
Nasal cavity enzymes involved in xenobiotic metabolism: effects on
  the toxicity of inhalants.

In: Crit Rev Toxicol (1991) 21(5):345-72

A decade ago, the ability of nasal tissues to metabolize inhalants
  was only dimly suspected. Since then, the metabolic capacities of
  nasal cavity tissues has been extensively investigated in mammals,
  including man. Aldehyde dehydrogenases, cytochrome P-450-dependent
  monooxygenases, rhodanese, glutathione transferases, epoxide
  hydrolases, flavin-containing monooxygenases, and carboxyl esterases
  have all been reported to occur in substantial amounts in the nasal
  cavity. The contributions of these enzyme activities to the induction
  of toxic effects from inhalants such as benzo-a-pyrene,
  acetaminophen, formaldehyde, cocaine, dimethylnitrosamine, ferrocene,
  and 3-trifluoromethylpyridine have been the subject of dozens of
  reports. In addition, the influence of these enzyme activities on
  olfaction and their contribution to vapor uptake is beginning to
  receive attention from the research community. Research in the next
  decade promises to provide answers to the many still unanswered
  questions posed by the presence of the substantial xenobiotic
  metabolizing capacity of the nasal cavity.

Institutional address: 
     Inhalation Toxicology Research Institute
     Lovelace Biomedical and Environmental Research Institute
     Albuquerque
     NM.


*****KOKYU TO JUNKAN. RESPIRATION AND CIRCULATION*****



Inoue M  Homma Y  Kawakami Y  
[Inorganic inhalants as one of the etiologic agents in idiopathic
  interstitial pneumonia]

In: Kokyu To Junkan (1985 Dec) 33(12):1423-33  (Published in Japanese)

[No Abstract Available]


*****MUTATION RESEARCH*****

Groschel-Stewart U  Mayer VW  Taylor-Mayer RE  Zimmermann FK  
Aprotic polar solvents inducing chromosomal malsegregation in yeast
  interfere with the assembly of porcine brain tubulin in vitro.

In: Mutat Res (1985 May) 149(3):333-8

A number of aprotic solvents which had previously been found to
  induce mitotic aneuploidy in yeast were tested for their effects on
  re-assembly of twice recycled tubulin from pig brain. Some of the
  solvents which were strong aneuploidy-inducing mutagens in yeast
  slowed down tubulin assembly in vitro at concentrations lower than
  those required for aneuploidy induction. Ethyl acetate, methyl
  acetate, diethyl ketone and acetonitrile fell into this category.
  Other strong aneuploidy-inducing agents like acetone and 2-
  methoxyethyl acetate accelerated tubulin assembly. Non-genetically
  active methyl isopropyl ketone and isopropyl acetate both accelerated
  assembly, whereas methyl n-propyl ketone and n-propyl acetate were
  weak inducers of aneuploidy and slowed down the rate and extent of
  assembly. Those chemicals which slowed down the assembly rate also
  reduced the extent of assembly. Most chemicals which accelerated
  assembly also led to an increased extent of assembly, with the
  exception of isopropyl acetate. At the higher concentrations,
  however, a maximum assembly rate was reached which was followed by a
  slow decline. Although a perfect correlation between effects on the
  induction of chromosomal malsegregation and the interference with
  tubulin assembly in vitro was not seen, the experiments with tubulin
  were carried out using this class of chemicals because some of them
  strongly induced mitotic aneuploidy under conditions which suggested
  tubulin to be the prime target. The lack of a perfect coincidence
  might be due to species differences between the porcine brain and the
  yeast spindle tubulin, or the test for aneuploidy induction may have
  been negative because the concentrations required for an effect on
  yeast tubulin may be greater than the general lethal toxicity limit.
  Bearing this reservation in mind, the results suggest that the yeast
  aneuploidy test has a considerable predictive value for mammalian
  mutagenicity.

Institutional address: 
     Institute for Zoology
     Technische Hochschule Darmstadt
     Federal Republic of Germany.


*****NIDA RESEARCH MONOGRAPH*****


Newell GR  Spitz MR  Wilson MB  
Nitrite inhalants: historical perspective.

In: NIDA Res Monogr (1988) 83:1-14

There are important reasons for considering nitrite inhalation as a
  factor in the development of AIDS-related KS in young male
  homosexuals. These are (1) the pharmacologic properties of amyl,
  butyl, and isobutyl nitrites, which are toxic; (2) the mutagenic,
  teratogenic, and carcinogenic products resulting from metabolism of N-
  nitroso compounds; (3) the potent carcinogenicity of N-nitroso
  compounds in 39 different animal species; and (4) the deleterious
  effects of volatile nitrites on human lymphocytes both in vitro and
  in vivo. Specifically related to this epidemic, there are additional
  reasons for pursuing the connection between nitrite inhalation and
  development of KS. These include: (1) the timing of the production
  and sales of volatile nitrites for use as recreational drugs and the
  subsequent outbreak of the AIDS epidemic (7 to 10 years); (2) the
  extensive use of nitrites among male homosexuals; (3) the virtual
  universal history of nitrite use by young male homosexuals in whom KS
  has developed during the past 3 years; and (4) the age group in which
  KS is developing is consistent with a cohort initially exposed 7 to
  10 years ago.

Institutional address: 
     Department of Cancer Prevention and Control
     University of Texas
     M.D. Anderson Hospital
     Houston 77030.


*****NORDISK MEDICIN*****


Hansen L  
[Organic solvents--an increasing problem in the occupational
  environment]

Organiske oplosningsmidler--et voksende arbejdsmiljoproblem.

In: Nord Med (1982 Dec) 97(12):299-301  (Published in Danish)

[No Abstract Available]

Institutional address: 
     Frederiksberg hospital
     DK
     Kbenhavn.


*****TIDSSKRIFT FOR DEN NORSKE LAEGEFORENING*****


Loberg T  Lberg T  
[Clinical neuropsychological investigation and personality assessment
  in alcohol abuse]

Klinisk neuropsykologisk undersokelse og personlighetsvurdering ved
  alkoholmisbruk.

In: Tidsskr Nor Laegeforen (1990 Feb 28) 110(6):721-4
  (Published in Norwegian)

In Norway, clinical neuropsychology is approved as an exclusive
  speciality in psychology. Clinical neuropsychological assessment is a
  well-proven method for which thorough validation studies and
  international norms are available. The method has a clear application
  in the assessment of dysfunctions and resources of alcohol-dependent
  inpatients. Cross-national comparisons show that neuropsychological
  findings are fairly consistent for alcohol-abusing individuals. A
  neuropsychological frame of reference is essential for secondary
  prevention among important groups. Some areas of central interest
  include alcohol and drug abuse among the elderly, occupational
  exposure to solvents, impulsiveness and violence, residual Attention
  Deficit Disorders, HIV/AIDS conditions, and other neuropsychiatric
  conditions.

Institutional address: 
     Hjellestad-Klinikken.


*****TOXICOLOGY AND APPLIED PHARMACOLOGY*****


Juchau MR  DiGiovanni J  Namkung MJ  Jones AH  
A COMPARISON OF THE CAPACITY OF FETAL AND ADULT LIVER, LUNG, AND
  BRAIN TO CONVERT POLYCYCLIC AROMATIC HYDROCARBONS TO MUTAGENIC AND
  CYTOTOXIC METABOLITES IN MICE AND RATS

In: Toxicol Appl Pharmacol (1979) 49(1):171-178

Preparations of S-9 fractions from the fetal brains of rats displayed
  a high capacity to convert 7,12-dimethylbenz(a)anthracene to
  metabolites mutagenic to Salmonella typhimurium tester strains TA-98,
  TA-100, and TA-1538. The same tissue was only minimally active or
  inactive in converting benzo(a)pyrene or N-2-fluorenylacetamide to
  mutagenic metabolites. Fetal brain tissues of mice were virtually
  inactive with respect to the bioactivation of each of the three
  procarcinogens but fetal pulmonary tissues of mice produced mutagen-
  generating activities that were five- to nine-fold above background
  with respect to 7,12-dimethylbenz(a)anthracene. Fetal hepatic and
  brain tissues of mice also catalyzed the conversion of each of the
  three promutagens to cytotoxic intermediates, but this phenomenon was
  not observed with fetal hepatic or brain tissues of rats. Analyses
  with high-pressure liquid chromatography demonstrated that brain
  tissues of fetal mice were very active in converting 7,12-
  dimethylbenz(a)anthracene to oxygenated metabolites, whereas the
  fetal brain tissues of rats were only minimally active. The
  chromatographic patterns observed also indicated that different
  metabolites were formed in the presence of S-9 fractions from rats
  vs. mice. The data are consistent with the hypothesis that the
  previously observed species difference in susceptibility to
  transplacental tumorigenesis by polycyclic hydrocarbons is related to
  differences in target organ biotransformation of these compounds. (21
  Refs)

Institutional address: 
     Dept. Pharmacology
     Univ. Washington
     Sch. Medicine
     Seattle
     WA
     98195


*****TOXICOLOGY LETTERS*****


Ikeda M  
Public health problems of organic solvents.

In: Toxicol Lett (1992 Dec) 64-65 Spec No:191-201

Selected topics of public health importance in toxicology of organic
  solvents are reviewed. Organic solvents are commonly used as mixtures
  rather than individual solvents, except for the case of degreasers.
  Nevertheless, toxicity of mixtures remain mostly to be studied. Among
  the solvents in general, toluene is apparently the most popular.
  Narcotic effects are common with all solvents (independent of
  chemical structure) at high concentrations, and result in an
  increased incidence of various CNS-related subjective symptoms at
  concentrations in excess of current occupational exposure limits.
  Chronic toxicity, teratogenicity and carcinogenicity seems to be
  related to a given chemical structure. Among the recently reported
  effects are blindness of "sniffers" by methanol inhalation and
  teratogenicity of ethylene glycol derivatives in experimental
  animals. In environmental health, pollution of ground water as well
  as the general atmosphere by chlorinated hydrocarbons has provoked
  serious public concern. In addition, emission of certain chemicals
  including chlorofluorocarbons is recognized to deplete ozone in
  stratosphere, which may result in human health effects.

Institutional address: 
     Department of Public Health
     Kyoto University Faculty of Medicine
     Japan.



Haverkos HW  Dougherty JA  
HEALTH HAZARDS OF NITRITE INHALANTS

In: Available from National Technical Information Service, Springfield,
  VA as NTIS/PB89-125496, 126 p., 1989.

Contents: Nitrite inhalants: historical perspective; Fate and
  toxicity of butyl nitrites; Acute toxicity of nitrite inhalants;
  Indications from animal and chemical experiments of a carcinogenic
  role for isobutyl nitrite; Toxicity of inhaled isobutyl nitrite in
  BALB/c mice: systemic and immunotoxic studies; Altered T-cell
  helper/suppressor ratio in mice chronically exposed to amyl nitrite;
  Effects of nitrites on the immune system of humans; Deliberate
  inhalation of isobutyl nitrite during adolescence: a descriptive
  study; Nitrite inhalants: contemporary patterns of abuse; and
  Epidemiologic studies-Kaposi's sarcoma vs opportunistic infections
  among homosexual men with AIDS.

Institutional address: 
     National Inst. on Drug Abuse
     Rockville
     MD


Horn KH  
[LIMITS AND POSSIBILITIES OF ANIMAL EXPERIMENTS WITH CARCINOGENIC
  INHALANTS]

In: Akad Wiss (1978)(2):52-62  (Published in German)

Animal inhalation studies with chemical carcinogens or cocarcinogens
  are reviewed and their relevance to cancer induction in humans is
  discussed. Current inhalation techniques are not completely reliable
  due to the short life span of the test animals (eg, rats and Syrian
  golden hamsters) and the long observation periods needed to
  approximate human exposures. With the development of more
  sophisticated inhalation equipment, more positive results may be
  obtained with definite carcinogens. Another difficulty with the
  inhalation method is the evaluation of a positive result; ie, whether
  a substance such as ferric trioxide is carcinogenic, cocarcinogenic,
  or causes cytopathological conditions that promote development.
  Intratracheal intubation and implantation techniques are more
  accurate in the production of respiratory tract tumors, and they are
  useful in screening possible carcinogenic inhalants. The system
  application method is adequate only when testing a known carcinogen
  whose activity (po or sc) is organ-specific in the test species.
  However, this technique is useful in that the exact dose can be
  applied and the synergistic and/or cocarcinogenic properties of the
  test substance can be ascertained. To relate respiratory tract
  carcinogenesis in man to animal experiments will require the
  perfection of application techniques and the identification of more
  suitable animal models. (61 Refs)

Institutional address: 
     No affiliation given


Lange WR  Haertzen CA  Hickey JE  Snyder FR  Dax EM  Jaffe JH  
Nitrite inhalants: patterns of abuse in Baltimore and Washington,
  D.C.

In: Am J Drug Alcohol Abuse (1988) 14(1):29-39

Nitrite inhalants, as drugs of abuse, have received a new prominence
  in the literature since their use has been associated with Kaposi's
  Sarcoma and possibly other manifestations of acquired
  immunodeficiency syndrome (AIDS). Changes in patterns and prevalence
  of use have not been investigated since the onset of the AIDS
  epidemic. We have examined the abuse patterns of nitrite inhalants
  (poppers) in several different groups. The use of poppers among drug
  abusers in the Baltimore-Washington, D.C. metropolitan area has
  remained constant over the past 5 years, with the prevalence of use
  being approximately 11% for recreational drug users and 22% for heavy
  abusers. Self-reported use by a homosexual group had decreased over
  the same time period. Sixty-nine percent of the homosexual sample had
  experience with nitrities, but only 21% had used them in the 6 months
  prior to being surveyed. The mean interval since last use was 25
  months, and since peak use, 4.1 years. Among substance abusers,
  nitrites appear to be a drug whose use starts late, with the mean age
  of first use being 25.6 years compared to 14.6 years for glue, 17.6
  years for marijuana, and 18.5 years for heroin. We found both
  heterosexual and homosexual groups utilize nitrites primarily to "get
  high," but homosexuals more often use them during overt sexual
  activity. Experience with amyl nitrite was much more prevalent than
  that with the butyl derivative in both populations. We conclude that
  the prevalence of nitrite abuse among drug users has not changed as a
  result of the AIDS epidemic, but such use appears to have decreased
  within the homosexual community.

Institutional address: 
     Addiction Research Center
     National Institute on Drug Abuse
     Baltimore
     Maryland 21224.

Dahl AR  Lewis JL  
Respiratory tract uptake of inhalants and metabolism of xenobiotics.

In: Annu Rev Pharmacol Toxicol (1993) 33:383-407

The combined impact of new research regarding the dosimetry of
  inhalants, discussed in early paragraphs of this review, and the
  rapidly developing knowledge regarding the location and substrate
  specificities of the enzymes responsible for xenobiotic metabolism
  should soon lead to new insights into the causes and prevention of
  cancer and other diseases of the respiratory tract and may provide
  insight into the design of drugs used in the treatment of respiratory
  tract disease. Among the developments to be expected within the next
  decade are the following: 1. The issue of extrapulmonary versus
  intrapulmonary activation of lung prodrugs and protoxicants will be
  resolved by validation of the different dosimetries predicted for
  highly lipophilic inhalants compared to less lipophilic ones. 2. The
  possibly complex roles of P450 isozymes 1A1 and 2D6 and other forms
  in the causation of human lung cancer will undoubtedly be better
  understood in the next few years. 3. Interspecies comparisons of
  respiratory tract enzyme activities--both activating and detoxicating-
  -will lead to improved use of laboratory animals as models for
  expected toxicological and pharmacological effects in humans. 4. The
  potential role of nasal uptake and metabolism in causing brain
  disease will be established or denied experimentally. 5. The complex
  relationships between host factors--such as hormone levels and the
  presence of inflammation--and metabolism-mediated toxicity will
  become clearer. 6. As new research results continue to illuminate the
  complexities of the interactions of xenobiotics with respiratory
  tract tissue, clues as to how best to administer drugs via the
  respiratory tract and understanding of changes in disease patterns--
  such as the recent shift in sites for lung cancer--will follow.

Institutional address: 
     Inhalation Toxicology Research Institute
     Albuquerque
     New Mexico 87185.


Dahl AR  Hadley WM  
Nasal cavity enzymes involved in xenobiotic metabolism: effects on
  the toxicity of inhalants.

In: Crit Rev Toxicol (1991) 21(5):345-72

A decade ago, the ability of nasal tissues to metabolize inhalants
  was only dimly suspected. Since then, the metabolic capacities of
  nasal cavity tissues has been extensively investigated in mammals,
  including man. Aldehyde dehydrogenases, cytochrome P-450-dependent
  monooxygenases, rhodanese, glutathione transferases, epoxide
  hydrolases, flavin-containing monooxygenases, and carboxyl esterases
  have all been reported to occur in substantial amounts in the nasal
  cavity. The contributions of these enzyme activities to the induction
  of toxic effects from inhalants such as benzo-a-pyrene,
  acetaminophen, formaldehyde, cocaine, dimethylnitrosamine, ferrocene,
  and 3-trifluoromethylpyridine have been the subject of dozens of
  reports. In addition, the influence of these enzyme activities on
  olfaction and their contribution to vapor uptake is beginning to
  receive attention from the research community. Research in the next
  decade promises to provide answers to the many still unanswered
  questions posed by the presence of the substantial xenobiotic
  metabolizing capacity of the nasal cavity.

Institutional address: 
     Inhalation Toxicology Research Institute
     Lovelace Biomedical and Environmental Research Institute
     Albuquerque
     NM.


Inoue M  Homma Y  Kawakami Y  
[Inorganic inhalants as one of the etiologic agents in idiopathic
  interstitial pneumonia]

In: Kokyu To Junkan (1985 Dec) 33(12):1423-33  (Published in Japanese)

[No Abstract Available]


Newell GR  Spitz MR  Wilson MB  
Nitrite inhalants: historical perspective.

In: NIDA Res Monogr (1988) 83:1-14

There are important reasons for considering nitrite inhalation as a
  factor in the development of AIDS-related KS in young male
  homosexuals. These are (1) the pharmacologic properties of amyl,
  butyl, and isobutyl nitrites, which are toxic; (2) the mutagenic,
  teratogenic, and carcinogenic products resulting from metabolism of N-
  nitroso compounds; (3) the potent carcinogenicity of N-nitroso
  compounds in 39 different animal species; and (4) the deleterious
  effects of volatile nitrites on human lymphocytes both in vitro and
  in vivo. Specifically related to this epidemic, there are additional
  reasons for pursuing the connection between nitrite inhalation and
  development of KS. These include: (1) the timing of the production
  and sales of volatile nitrites for use as recreational drugs and the
  subsequent outbreak of the AIDS epidemic (7 to 10 years); (2) the
  extensive use of nitrites among male homosexuals; (3) the virtual
  universal history of nitrite use by young male homosexuals in whom KS
  has developed during the past 3 years; and (4) the age group in which
  KS is developing is consistent with a cohort initially exposed 7 to
  10 years ago.

Institutional address: 
     Department of Cancer Prevention and Control
     University of Texas
     M.D. Anderson Hospital
     Houston 77030.


Haverkos HW  Dougherty JA  
HEALTH HAZARDS OF NITRITE INHALANTS

In: Available from National Technical Information Service, Springfield,
  VA as NTIS/PB89-125496, 126 p., 1989.

Contents: Nitrite inhalants: historical perspective; Fate and
  toxicity of butyl nitrites; Acute toxicity of nitrite inhalants;
  Indications from animal and chemical experiments of a carcinogenic
  role for isobutyl nitrite; Toxicity of inhaled isobutyl nitrite in
  BALB/c mice: systemic and immunotoxic studies; Altered T-cell
  helper/suppressor ratio in mice chronically exposed to amyl nitrite;
  Effects of nitrites on the immune system of humans; Deliberate
  inhalation of isobutyl nitrite during adolescence: a descriptive
  study; Nitrite inhalants: contemporary patterns of abuse; and
  Epidemiologic studies-Kaposi's sarcoma vs opportunistic infections
  among homosexual men with AIDS.

Institutional address: 
     National Inst. on Drug Abuse
     Rockville
     MD


Title:       Dangerous inhalants are increasingly popular among adolescents.

------------------------------------------------------------------------------

Subjects:    Teenagers_Drug use
             Solvent abuse_Research


Gasoline, felt-tipped pens, deodorants and nail-polish remover are gaining
popularity among young people -- as drugs. Inhaling, sniffing or, as it's
called on the street, "huffing" chemical substances is an easy, cheap and
legal way to get a quick high. But many treatment professionals don't seem to
know it. "This is one of those phenomena where people on the street are often
more knowledgeable than so-called experts in public health and drug
treatment," says Dwight B. Health, Ph.D., a professor of anthropology at Brown
University.

Fully 29 percent of street youth said they sniffed, according to a recent
study by the Addiction Research Foundation. Thirty-nine percent cited
inhalants as "major problems," second only to crack. Inhalants give users an
initial euphoria that may include light-headedness, exhilaration and sometimes
hallucinations. Some users experience a sense of empowerment, which can result
in dangerous behavior. The first inhalation often wears off in just a few
minutes, but most users breathe deeply and repeatedly for longer periods and
often concentrate the material in a plastic bag or other container.

Sniffing inhalants

While under the influence, the user may experience drooling, sneezing, nausea,
coughing, hypersensitivity and progressive lack of coordination. The chemicals
in inhalants can block the nasal passages and coat the lungs. Long-term
effects include weight loss; frequent nosebleeds; sores in the nose, mouth and
throat; and damage to the liver, kidney and bone marrow. Depression is common
among users, but whether it is a symptom of the inhalant or a condition that
precedes drug use is not certain, Heath says.

Irritability, paranoia and hostility are other emotional hazards of sniffing

Citation:    The Addiction Letter, August 1993 v9 n8 p1(2)

------------------------------------------------------------------------------

Title:       Dangerous inhalants are increasingly popular among adolescents.

------------------------------------------------------------------------------

Subjects:    Teenagers_Drug use
             Solvent abuse_Research

Gasoline, felt-tipped pens, deodorants and nail-polish remover are gaining
popularity among young people -- as drugs. Inhaling, sniffing or, as it's
called on the street, "huffing" chemical substances is an easy, cheap and
legal way to get a quick high. But many treatment professionals don't seem to
know it. "This is one of those phenomena where people on the street are often
more knowledgeable than so-called experts in public health and drug
treatment," says Dwight B. Health, Ph.D., a professor of anthropology at Brown
University.

Fully 29 percent of street youth said they sniffed, according to a recent
study by the Addiction Research Foundation. Thirty-nine percent cited
inhalants as "major problems," second only to crack. Inhalants give users an
initial euphoria that may include light-headedness, exhilaration and sometimes
hallucinations. Some users experience a sense of empowerment, which can result
in dangerous behavior. The first inhalation often wears off in just a few
minutes, but most users breathe deeply and repeatedly for longer periods and
often concentrate the material in a plastic bag or other container.

Sniffing inhalants

While under the influence, the user may experience drooling, sneezing, nausea,
coughing, hypersensitivity and progressive lack of coordination. The chemicals
in inhalants can block the nasal passages and coat the lungs. Long-term
effects include weight loss; frequent nosebleeds; sores in the nose, mouth and
throat; and damage to the liver, kidney and bone marrow. Depression is common
among users, but whether it is a symptom of the inhalant or a condition that
precedes drug use is not certain, Heath says.

Irritability, paranoia and hostility are other emotional hazards of sniffing
solvents. Mental confusion and fatigue can forebode tremors and brain damage
in heavy users. And repeated breathing can result in seizures, unconsciousness
and death from heart failure, suffocation or accidents. Deep sniffing can kill
even first-time users, says Heath, adding that sniffing is a favored way of
committing suicide among young people in some communities.

As with a lot of other drugs, regular use raises tolerance, and greater
amounts are needed to achieve the same effects. Young people rarely become
physically addicted to inhalants, with full-blown withdrawal symptoms if they
stop inhaling; but psychological dependence, or craving, is common, says
Heath.

"The dangers are real and serious," he says. What worries him most is the lack
of attention the danger of inhaling solvents gets. "Although this is a drug
threat that is imminent, it has hardly been publicized, even during this time
of governmental overreaction to alcohol and other regulated substances," he
says. "Part of the reason is that the threat comes from unregulated
substances, highlighting the fallacy of our long-misguided emphasis on
attempting to curtail supply rather than addressing demand. The irony is that,
unlike so-called controlled, or hard, drugs, many [inhalants] are toxic in
dosages that are commonplace, with fatal outcomes not uncommon."

While the use of inhalants is a one-time experiment for many young people,
others fall into habitual use. These regular users tend to be poor, do badly
in school, and come from unstable families. Until recently, it was a problem
known only to a few public health officials for its prevalence among Inuit,
Native American, Australian Aborigine and homeless Central and South American
children.

"In much the same way that AIDS was long ignored because it appeared to be
blacks and homosexuals who were most involved, sniffing may long have been
ignored as a curious affliction among populations who themselves have tended
to be ignored," Heath says. "But now we know that sniffing is not restricted
to marginal populations."

Researchers are beginning to pay attention to the problem of solvent-inhaling,
and they are finding that more and younger children are involved than they
imagined, Heath says. The peak years -- eighth to 10th grades -- were first
included in a survey of U.S. drug use in 1991, by which time the number of
high school seniors who had experimented with inhalants had increased to 18
percent, from 12 percent a decade earlier, according to the University of
Michigan's Institute for Social Research.

"In anthropological terms, it is interesting to see this as an instance where,
contrary to the usual finding, a pattern of behavior that characterized
populations that were marginal in many senses -- geographically remote, poor,
with cultures that are often depreciated -- diffused upward or inward from the
periphery to the center, from folk to urban culture, and from various
frontiers to the metropoles," Heath says. "In terms of public health and
social welfare, it is important to be alerted to a set of risks that few
practitioners had thought about before."

Heath says there's no data to support the World Health Organization's
assertion that solvents are a stepping stone to other kinds of drug use. "As
is so often the case, they are addressing an issue that has big importance to
a few people, but they're coming at it from an inappropriately ethnocentric
pre-judging perspective," he says. "We need not concern ourselves with
imagined consequences when the real and immediate risks of abusive inhaling by
vulnerable young people are considered."


Citation:    The Brown University Child and Adolescent Behavior Letter, August
             1993 v9 n8 p1(3)

------------------------------------------------------------------------------

Title:       Dangerous inhalants are increasingly popular among adolescents.
             (includes related article on symptoms)

------------------------------------------------------------------------------

Subjects:    Aerosol sniffing_Physiological aspects
             Teenagers_Drug use
             Solvent abuse_Demographic aspects


Gasoline, felt-tipped pens, deodorants and nail-polish remover are gaining
popularity among young people -- as drugs. Inhaling, sniffing or "huffing" (as
it's called on the street), chemical substances is an easy, cheap and legal

Press  for more (? for help) ! 

way to get a quick high. But not all treatment professionals seem to know it.

"This is one of those phenomena where people on the street are often more
knowledgeable than so-called experts in public health and drug treatment,"
says Dwight B. Heath, Ph.D., a professor of anthropology at Brown University.

Fully 29 percent of street youth said they sniffed, according to a recent
study by the Addiction Research Foundation. Thirty-nine percent cited
inhalants as "major problems," second only to crack.

Quick high

Inhalants give users an initial euphoria that may include light-headedness,
exhilaration and sometimes hallucinations. Some users experience a sense of
empowerment, which can result in dangerous behavior.

The first inhalation often wears off in just a few minutes, but most users
breathe deeply and repeatedly for longer periods and often concentrate the
material in a plastic bag or other container.

While under the influence, the user may experience drooling, sneezing, nausea,
coughing, hypersensitivity and progressive lack of coordination. The chemicals
in inhalants can block the nasal passages and coat the lungs. Long-term

Press  for more (? for help) ! 

effects include weight loss; frequent nosebleeds; sores in the nose, mouth and
throat; and damage to the liver, kidney and bone marrow. Depression is common
among users, but whether it is a symptom of the inhalant or a condition that
precedes drug use is not certain, Heath says.

Irritability, paranoia and hostility are other emotional hazards of sniffing
solvents. Mental confusion and fatigue can foretell tremors and brain damage
in heavy users. And repeated inhaling of these substances can result in
seizures, unconsciousness and death from heart failure, suffocation or
accidents. Deep sniffing can kill even first-time users, says Heath, adding
that it is a favored way of committing suicide among young people in some
communities.

As with a lot of other drugs, regular use raises the user's tolerance, and
greater amounts are needed to achieve the same effect. Young people rarely
become physically addicted to inhalants, with full-blown withdrawal symptoms
if they stop inhaling; but psychological dependence, or craving, is common,
according to Heath.

"The dangers are real and serious," he says. What worries him most is the lack
of attention the danger of inhaling solvents gets. "Although this is a drug
threat that is imminent, it has hardly been publicized, even during this time
of governmental overreaction to alcohol and other regulated substances," he

Press  for more (? for help) ! s

Citation:    The Brown University Child and Adolescent Behavior Letter, August
             1993 v9 n8 p1(3)

------------------------------------------------------------------------------

Title:       Dangerous inhalants are increasingly popular among adolescents.
             (includes related article on symptoms)

------------------------------------------------------------------------------

Subjects:    Aerosol sniffing_Physiological aspects
             Teenagers_Drug use
             Solvent abuse_Demographic aspects

Gasoline, felt-tipped pens, deodorants and nail-polish remover are gaining
popularity among young people -- as drugs. Inhaling, sniffing or "huffing" (as
it's called on the street), chemical substances is an easy, cheap and legal
way to get a quick high. But not all treatment professionals seem to know it.

"This is one of those phenomena where people on the street are often more
knowledgeable than so-called experts in public health and drug treatment,"
says Dwight B. Heath, Ph.D., a professor of anthropology at Brown University.

Fully 29 percent of street youth said they sniffed, according to a recent
study by the Addiction Research Foundation. Thirty-nine percent cited
inhalants as "major problems," second only to crack.

Quick high

Inhalants give users an initial euphoria that may include light-headedness,
exhilaration and sometimes hallucinations. Some users experience a sense of
empowerment, which can result in dangerous behavior.

The first inhalation often wears off in just a few minutes, but most users
breathe deeply and repeatedly for longer periods and often concentrate the
material in a plastic bag or other container.

While under the influence, the user may experience drooling, sneezing, nausea,
coughing, hypersensitivity and progressive lack of coordination. The chemicals
in inhalants can block the nasal passages and coat the lungs. Long-term
effects include weight loss; frequent nosebleeds; sores in the nose, mouth and
throat; and damage to the liver, kidney and bone marrow. Depression is common
among users, but whether it is a symptom of the inhalant or a condition that
precedes drug use is not certain, Heath says.

Irritability, paranoia and hostility are other emotional hazards of sniffing
solvents. Mental confusion and fatigue can foretell tremors and brain damage
in heavy users. And repeated inhaling of these substances can result in
seizures, unconsciousness and death from heart failure, suffocation or
accidents. Deep sniffing can kill even first-time users, says Heath, adding
that it is a favored way of committing suicide among young people in some
communities.

As with a lot of other drugs, regular use raises the user's tolerance, and
greater amounts are needed to achieve the same effect. Young people rarely
become physically addicted to inhalants, with full-blown withdrawal symptoms
if they stop inhaling; but psychological dependence, or craving, is common,
according to Heath.

"The dangers are real and serious," he says. What worries him most is the lack
of attention the danger of inhaling solvents gets. "Although this is a drug
threat that is imminent, it has hardly been publicized, even during this time
of governmental overreaction to alcohol and other regulated substances," he
says. "Part of the reason is that the threat comes from unregulated
substances, highlighting the fallacy of our long-misguided emphasis on
attempting to curtail supply rather than addressing demand. The irony is that,
unlike so-called controlled, or hard, drugs, many [inhalants] are toxic in
dosages that are commonplace, with fatal outcomes not uncommon."

Not just their problem

While the use of inhalants is a one-time experiment for many young people,
others fall into habitual use. These regular users tend to be poor, do badly
in school, and come from unstable families. Until recently, it was a problem
known only to a few anthropologists and public health officials for its
prevalence among Inuit, Native Americans, Australian Aborigines and homeless
Central and South American children.

"In much the same way that AIDS was long ignored because it appeared to be
blacks and homosexuals who were most involved, sniffing may long have been
ignored as a curious affliction among populations who themselves have tended
to be ignored," Heath says. "But now we know that sniffing is not restricted
to marginal populations."

Researchers are beginning to pay attention to the problem, and they are
finding that more and younger children are involved than they imagined, Heath
says. The peak years -- eighth to 10th grades -- were first included in a
survey of U.S. drug use in 1991, by which time the number of high school
seniors who had experimented with inhalants had increased to 18 percent, from
12 percent a decade earlier, according to the University of Michigan's
Institute for Social Research.

"In anthropological terms, it is interesting to see this as an instance where,
contrary to the usual finding, a pattern of behavior that characterized
populations that were marginal in many senses -- geographically remote, poor,
with cultures that are often depreciated -- diffused upward or inward from the
periphery to the center, from folk to urban culture, and from various
frontiers to the metropoles," Heath says. "In terms of public health and
social welfare, it is important to be alerted to a set of risks that few
practitioners had thought about before."

Heath says there are no data to support the World Health Organization's
assertion that solvents are a stepping stone to other kinds of drug use. "As
is so often the case, they are addressing an issue that has big importance to
a few people, but they're coming at it from an inappropriately ethnocentric
pre-judging perspective," he says. "We need not concern ourselves with
imagined consequences when the real and immediate risks of abusive inhaling by
vulnerable young people are considered."