Animal Studies Misrepresent Alkyl Nitrites Impact on Humans
Animal studies are frequently cited on the web in articles about the devastating health effects of inhaling alkyl nitrite Poppers. These stories add to the often repeated body of information that is constantly circulated and reposted in web searches. It is hard to determine the validity and reliability of the claims that are made because the conditions under which the studies are conducted, and the reasons that lead to the “research” being undertaken, are suspect.
There are a number of reasons for this confusion. Chief among them is the conditions under which the nitrites are administered. A second issue is the significant doses that are administered relative to the size of the mice. Typical of the cloud of inaccuracy surrounding the topic, many of the articles either pass on outdated and inaccurate information, or perpetuate information that is long proven to be flat out incorrect. This article will explore some of the more prevalent falsehoods and why they are repeated over and again.
Why Does Recycling These Distractors Matter?
Understanding why these misrepresentations are significant is important. Political decisions and laws have passed regulating alkyl nitrite compounds based on these “scientific” data. Most people who read these statements do not have the time, inclination or educational resources to wade through the facts in these cases. The primary question raised is whether the scientific processes and conclusions are sound and based on sufficient data to make wide ranging generalizations about the health consequences.
When these inaccurate or outdated conclusions are used, the problem magnifies itself exponentially. Most articles presenting this data do not qualify their remarks so the reader can weigh the matter and pass judgment based on facts. Using animal studies to vilify inhaling alkyl nitrites for recreational purposes contributes to the web of lies that is often repeated as unquestionable fact! People tend to believe what they read on the Internet and hear in the news is reliable.
Major Animal Studies Represent Huge Doses Much Greater Than Any Human Would Consume
The National Institute of Health (NIH) is front and center in the spreading of exaggerated information about the health effects of inhaling alkyl nitrites. Citing Soderberg, Flick and Barnett’s studies from the 1980’s, the NIH relies heavily on the study which allegedly proved, “Leukopenia and altered hematopoietic activity in mice exposed to the abused inhalant, isobutyl nitrite.”
The study was used to prove that abuse of isobutyl nitrite might be a risk factor for AIDS and Kaposi’s Sarcoma. Both of these assertions have been subsequently disproven, yet these studies and articles continue to show up in Internet searches.
Without being too technical, they alleged significant health impacts including being, “immunotoxic to mice, severely compromising T-dependent antibody responses and cytotoxic T cell and macrophage tumoricidal activity. In addition, exposure to the inhalant dramatically reduced spleen cellularity.’ Several other claims were made including developing anemia, blood irregularities, and bone marrow complications.
The Doses Would Poison Anyone
The study goes on to describe the doses used in the experiment. “Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 minutes/day for 14 days.” What they are describing here is essentially a gas chamber administration of alkyl nitrites to the mice.
While some of the injury repaired itself, other negative effects lingered. They report, “Peripheral blood erythrocyte and leukocyte counts returned to normal levels by 7 days after the final exposure, as did the number of BFU-E. The number of CFU-GM remained depressed, however, even after 7 days of recovery. This data suggests that repeated exposure depleted cells and that erythropoiesis was stimulated, apparently at the expense of myelopoiesis.”
Recreational users of alkyl nitrites would never be able to replicate either the doses or the duration of exposure to the isobutyl nitrite. More on that later.
Let’s Analyze the Dose Versus Body Mass
To compare the outcome of the impact of exposure, one needs to look at the subjects. A typical American male weighs 180.62 pounds, 81.928 kilograms. The mice used in the studies weighed 30 grams, or .03 kg. Here is the absurdity of the “science”.
A mouse weighs 30 grams in this study, that is .03 kilograms compared with a typical American male weighing in at 180.62 pounds or 81.928 kilograms. The man weighs 2,731 times more than the mouse, yet the process includes administering a “dose” of 900 ppm. “Users estimate they can derive 40 “doses” from a typical room odorizer, yielding approximately 0.2 ml per self-administration (lsraelstam et al. 1978).”
That translates into 200ppm. The mice received 4.5 times the typical human dose of 200ppm of Isobutyl Nitrite (ISBN) mixed in breathing air for 45 minutes, using an exposure chamber. The huge imbalance is that a 4.5 times greater dose is administered to a body 3.6 one thousandth the size of the human for comparative purposes.
That is like comparing the impact on a piece of glass by a grain of sand and a boulder. There is obviously, no comparison to be made! This data was also restated in “Inactivation of Hepatic Enzymes by Inhalant Nitrite – In Vivo and In Vitro Studies”. Same exaggerations repeated and re-blogged over and over again.
How was the Human Dose Computed?
Users estimate they can derive 40 “doses” from a typical room odorizer, yielding approximately 0.2 ml per self-administration (lsraelstam et al. 1978) . [0.2ml X 1000ppm = 200ppm human dose] according to calculator/converter found at http://www.endmemo.com/sconvert/ppmml_l.ph .
This estimate is neither a dose nor an exposure concentration, but a rate of loss of a volatile material from an open container. There have been no studies that describe either the absorbed dose or the exposure concentrations that are effective in producing smooth muscle relaxation, alterations in cardiovascular function, behavioral impairment, or self-administration under the brief exposure conditions typical of self-administration.
However, Pryor et al. (1989) did expose rats to isobutyl nitrite for 15 to 60 seconds, at concentrations that increased gradually in the exposure chamber. The LC50s expressed as a peak concentration ranged from 4.5 to 4.8 percent. The slope of the lethality function was influenced by the rate of change of concentration. A constant concentration-time product relationship was not obtained in this study, or in that of Klonne et al. (1987), suggesting that the dramatic acute effects of the agent may alter the pharmacokinetics and exaggerate the toxicity of these agents.
The Study’s Conclusion is Inconclusive
Even after declaring the negative impacts of the administration, the researchers described the recovery and temporary nature of any health impacts. Finally, they acknowledged, “Although our data indicated that ISBN exposure led to marked decreases in the enzyme activity studied when the mice were immediately sacriﬁced after exposure, the enzyme activity returned to control values when the animals were allowed to recover for 24 hours after exposure. This apparent regeneration in enzyme activity suggests that the inhibitory effects of nitrite exposure are reversible within a 24-hour period.”
They continued, “A similar rapid recovery in enzyme activity was observed even when mice were repeatedly exposed to ISBN for 6 days, suggesting that the effects of nitrite exposure on liver enzyme activity may not be cumulative. However, the relationships among exposure dose, frequency, and duration of enzyme inhibition were not deﬁned by the present studies.”
The ultimate kicker in the use of these studies to predict impact on humans is their conclusion that they cannot draw a conclusion. They conclude: “Determining the applicability of these results to humans will require further investigation.” (pE304)
Drugabuse.gov Repeats the Myths
Negative physical outcomes are cited in the archives of Drugabuse.gov in their 1977 monograph Review of Inhalants: Euphoria to Dysfunction. While citing numerous studies pertaining to the uses and the populations that use nitrites, they then cite the list of potential side effects from the “most commonly used and abused aliphatic nitrite,” amyl nitrite. Interestingly, most citations are for animal studies, which frequently result in mass quantities and extreme results. They report:
The use of amyl nitrite may be accompanied by medical complications. Limited toxicological data have been available. When given to mice by i.p. injection, the LD50 was 130mg/kg. When given by i.v. the LD50 was 51 mg/kg Dewey et. al., 1973). When dogs were administered amyl nitrite i.v., low doses elicited tremors and ataxia, while higher doses produced convulsions and death (Dewey et al., 1973). When these same investigators exposed the dogs to the drug by inhalation, one dog became quiet and another ataxic for a short period. When they were subjected to repeated inhalation doses of amyl nitrite at 20- to 90-second intervals for up to 7 minutes. varying degrees of pharmacologic effects were noted, ranging from no effect to ataxia, gagging, vomiting, urination, defecation, and even brief convulsions. These effects seemed to be somewhat related to the frequency of dose and the number of doses.
Many of us are old enough to remember similar studies involving large doses of artificial sweeteners, that were later discredited because the doses represented significant overexposure to that typically used by humans.
The reference to human effects, however, are scant in comparison and do not appear as scientific as the animal studies. They continue, “Other side effects have been noted in people who have used or abused this drug, including dizziness, headache, tachycardia, hypotension, syncope, and increased intraocular pressure (Everett, 1972, 1975b); Gay and Sheppard, 1973; Hollister, 1975a, 1975b; Louria, 1970; Pearlman and Adams, 1970).
Nitrites in general have also been associated with methemoglobinemia and rare sudden deaths (Louria, 1970).” Amyl nitrite is contraindicated in certain persons who have cardiovascular problems (Everett, 1975b; Hollister, 1975a, 1975b).” they then opine, “If abuse of such drugs continues to escalate medical complications may be seen more frequently.” (emphasis added)
They also discredit their evidence further by stating that, “Few if any investigations have been conducted on the effects of butyl nitrites and related components contained in over-the-counter products such as Locker Room or Rush. Clearly the government agency position clearly promoted the notion that inhaling nitrites has toxicological outcomes, yet they are based on exaggerated data.
Other Studies Repeat the Exaggerated Dosing Conditions
In her study The Art of Scientific Scrutiny: Investigating the Poppers-AIDS Hypothesis, Christine Weber, B.Sc. reiterates the inappropriate dosing of animal studies to portray human damage.
She looks at a study completed by a group of researchers at M.D. Hospital in Houston, Texas (Hersh et al. 1983). The researchers investigated the effects of butyl nitrite (a type of alkyl nitrite) on laboratory cultures of white blood cells. Hersh and colleagues reported that “when exposed to a 1% concentration of butyl nitrite for 24 hours, many of these cells were killed, while at 0.5%, the cell number and viability were unaffected. What do these findings mean for an average human being?
To establish a 1% concentration of butyl nitrite in an average human with six liters of blood even for a brief moment (we are not considering the 24 hour time period here yet), 60 mL of butyl nitrite needs to be added to the blood.
A bottle of poppers contains 10 to 12 mL of the compound. This means that five or six bottles of the compound would have to be injected into a human to replicate the conditions of the experiment. Since nitrites are inhaled rather than injected (injecting nitrites is toxic) and only a small fraction of the compound is actually absorbed by the lungs, this study tells us nothing in reality except that a 1% concentration of butyl nitrite kills cells in a test tube. (Voeller 1986)
Sorting the Truth and Facts About Poppers
Counteracting 40 years of distorted and inaccurate information about the health impact of inhaling poppers for recreational, sexual, relationship and other personal purposes is a daunting task since an object in motion is a lot harder to stop.
So much information has been disseminated that has built on and generalized the myths. Repeating the outcomes of animal studies to demonstrate the health hazards on inhaling alkyl nitrites is the first root of misinformation in the exaggerated medical claims about poppers. There are no disclaimers that the data are wrong, old or based on flawed reasoning and processes. The studies are reported as valid repeatedly, with no challenges to their inaccuracy.