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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.

*****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]

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]

*****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.

*****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]

*****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***** 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.

*****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.

*****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.


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.


*****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

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]

*****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.

*****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.

*****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.

*****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.

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

Haverkos HW
Kaposi's sarcoma and nitrite inhalants.
In: Adv Biochem Psychopharmacol (1988) 44:165-72

[No Abstract Available]

*****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)

*****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.

*****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) *****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.

*****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.

*****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.

*****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.

*****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.

*****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.

*****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]

*****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.

*****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)

*****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.

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)

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.

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.

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.

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]

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.

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

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 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

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."