Piperonyl butoxide, dangerous or not ?
Introduction to Piperonyl Butoxide (PBO)
Piperonyl Butoxide, also known as PBO or 5-[2-(2-Butoxyethoxy)ethoxymethyl]-6-propyl-1,3-benzodioxole (chemical formula C19-H30-O5), is a synergist often used in insecticides.
Still authorised for use in organic farming, PBO has long been the subject of controversy.
The health and safety data sheet (MSDS) for this product gives an idea of its toxicity in its pure state.
- R23 R24 R25 : Toxic by inhalation, in contact with skin and if swallowed.
- R40 : Suspected carcinogenic effect: insufficient evidence.
- R50/53: Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
After extensive research in the literature, mainly Anglo-Saxon, we have managed to find a certain amount of information on Piperonyl Butoxide. We are providing you with this 'raw' information as we found it.
Main source pesticides and you vol. 26, No. 1, 2006.
History of Piperonyl Butoxide (PBO)
In the late 1930s, American pesticide manufacturers began looking for a way to increase the potency of pyrethrum imported from Japan.
PBO was synthesised in 1947 by Herman Wachs from safrole, a naturally occurring raw material.
In 1952, the United States began manufacturing PBO in large quantities .
Since then, it has been used as a synergist in most commercial insecticides.
It increases the toxicity of the active ingredients, which means that less insecticide can be used while maintaining the effectiveness of the final product.
In general, there are between 5 and 10 units of PBO for 1 unit of active ingredient.
The active ingredient may be of synthetic origin, such as pyrethroids, or of natural origin, such as pyrethrins.
What is a synergist ?
A synergist is a chemical added to pesticides to increase the toxicity of the active ingredients, making the pesticide more lethal. But it can also compromise the detoxification mechanisms of non-target species, including humans.
Its action is to slow down the breakdown of toxic chemicals in insects.
The first step in the degradation of many types of chemicals in insects is oxidation by a group of microsomal enzymes called P450 mono-oxygenases, located in the liver.
By inhibiting the activity of these enzymes, it prevents the metabolism of many types of molecules, including insecticides.
This mechanism enables the pesticide to remain in its toxic form for longer periods.
A high dose of PBO makes an organism temporarily vulnerable to a variety of toxic chemicals.
Not only does PBO kill organisms, it is known to interfere with reproduction in many types of wildlife at concentrations much lower than those required for mortality.
PBO also inhibits the degradation of toxic chemicals in soil. Its concentration is generally between five and ten times that of the pesticide .
Study of Piperonyl Butoxide (PBO)
Although PBO is rarely used on its own, most studies have examined it separately.
When combined with pyrethrins or other insecticides, the toxic effects of the chemicals cannot simply be added together. The effects are multiplicative.
Assessing PBO alone gives results of limited value. Most studies, including the dossier published in April 2005 by the US Environmental Protection Agency (US EPA), fail to address the health effects of combined PBO. In April 2005, the EPA launched a public interest investigation into PBO.
The main concern expressed by the public about this dossier is that the EPA should not assess PBO alone. It should assess the synergistic effects with the materials with which it is generally marketed, and mainly in urban environments where it is commonly used.
PBO is commonly sprayed by municipalities for mosquito control.
Children's exposure to PBO is a cause for concern because of their particular vulnerability.
Where can I find Piperonyl Butoxide (PBO) ?
There are currently over 2,500 insecticides containing PBO. These include aerosols, repellents, pediculicides (lice killers), agricultural or garden pesticides (vegetable, fruit, lawn, ornamental plants, etc.), mosquito control products, termite treatments, veterinary pesticides and insecticides for human clothing and bedding .
According to EPA surveys, PBO is one of the most commonly used ingredients in insecticides.
It is currently found in approximately 1600 registered pest control products. 
On labels, PBO is sometimes listed as an active ingredient, but may also be considered an inert ingredient and therefore not listed or listed under another name.
Piperonyl Butoxide (PBO) residues in our food
Because of its widespread use, PBO can end up in our environment.
A recent study of pregnant women in northern Manhattan and the Bronx found PBO in over 80% of the air samples taken from their homes.
In addition, PBO residues are regularly found in food, particularly lettuce, lemons, spinach and tomatoes, as well as basil, chives, coriander, herbs, mint, pears, peppers, oranges , squash and other fruits and vegetables. 
The EPA states that the acute dietary risk is very low, and is below the acceptable intake limit .
Piperonyl Butoxide (PBO) and Cancer
The EPA classifies piperonyl butoxide in group C (possible human carcinogen)  but there is currently no data to prove that it is likely to present a carcinogenic risk for humans.
The only information available comes from animal studies.
Several studies have shown that treating rats with high doses of PBO causes an increase in liver cancer and a very slight increase in thyroid cancer. 
Piperonyl Butoxide (PBO) and mutagenic effects
It is generally accepted that PBO does not have a significant potential for genetic alteration. [26-27]
This conclusion is not universally accepted, and some studies have evidence of genetic damage. [28-29]
Piperonyl Butoxide (PBO) and the immune system
PBO weakens the immune system by inhibiting the lymphocyte response (the body's ability to defend itself against foreign bodies). 
Piperonyl Butoxide (PBO) and acute toxicity
Studies suggest that by interfering with hormone metabolism, PBO can damage humeral organs such as the thyroid, adrenal glands and pituitary gland. 
In short-term studies with laboratory animals, PBO is considered to be of low toxicity.
- The acute oral LD50 was established at 6.15 g/kg for rats and 2.6 g/kg for mice .
- The inhalation LD50 for rats is greater than 5.9 g/kg.
- The dermal LD50 for rabbits is 200 mg/kg.
- The lethal dose for humans is 5.15 g/kg .
Note : LD50 = dose that kills half the population tested.
The symptoms caused by ingestion of PBO at high doses are nausea, cramps, vomiting and diarrhoea. 
Inhalation of large quantities of PBO can cause lacrimation, salivation and laboured breathing.  accumulation of fluids in the lungs  ,and may cause respiratory tract problems such as asthma.
Repeated skin and eye contact has shown mild irritation, but does not cause long-term damage. 
Overdoses of PBO can cause instability, coma, convulsions and brain damage in rats .
Most deaths in studies have been attributed to haemorrhage in the digestive system, particularly the large intestine.
Acute exposure in animals also triggered liver problems, anaemia and loss of appetite, as well as kidney disturbances, nasal bleeding, loss of muscle coordination and abdominal pain. 
Piperonyl Butoxide (PBO) and effects on reproduction
The main effect of prolonged exposure to PBO in animals is an increase in liver, thyroid and kidney weights and a decrease in body weight.
These symptoms were observed in a diet of 52.8 mg / kg or more per day in a chronic study with dogs. 
Piperonyl Butoxide (PBO) and long-term toxicity
PBO has been shown to affect certain reproductive functions, but there is currently no evidence that it affects fertility. 
A 2011 study found a significant association between piperonylbutoxide measured in ambient air during the third trimester of pregnancy, and delayed mental development at 36 months.
Children who were most exposed (> 4.34 ng/m3 of air) lost 3.9 points on the mental development index compared with those who had lower exposures.
The person responsible for this study stated: "This drop in IQ points is similar to that observed in exposure to lead".
Two laboratory studies on rats show that when mothers were exposed to high concentrations of PBO, there was an increase in birth defects and foetal death. 
Rats exposed to PBO over two years of experimentation showed testicular atrophy, decreased seminal vesicle weight, and increased ovarian weight. 
Piperonyl Butoxide (PBO) and neurotoxicity
Data have shown that PBO interferes with the enzymes that maintain sodium and calcium homeostasis in the brain and nervous system, which could affect neuronal response[36-37].
It also increases the neurotoxicity of other compounds associated with it.
Despite these data, the EPA considers these neurotoxic effects to be slight and maintains that PBO poses no neurological risk.
Behavioural changes have also been observed. In a laboratory experiment, exposed rats had more difficulty navigating a maze than unexposed rats. Exposed rats travelled longer distances and turned more often in the maze.
It also induces changes in the olfactory behaviour of the offspring of exposed dams.
These data show that PBO has the ability to affect mammalian behaviour.
Piperonyl Butoxide (PBO) and other chronic effects
Research on rats has shown that PBO can cause intestinal ulcers and bleeding. 
Various studies frequently find liver damage as well as kidney damage. 
They have also found that long-term ingestion of PBO causes anaemia, a decrease in the amount of haemoglobin in the blood and an increase in blood cholesterol levels in rats, and that it can create damage to the larynx.
Some reports indicate that it can cause breathing difficulties, accumulation of fluid in the lungs, nasal bleeding, abdominal swelling and loss of the ability to coordinate muscle movements.
Piperonyl Butoxide (PBO) and effects on the environment
PBO is considered moderately toxic to fish, moderately to highly toxic to invertebrates (including crustaceans and insects), and highly toxic to amphibians.
In one study, concentrations of less than one part per million (ppm) killed water fleas, shrimps and oysters.
It is also highly toxic to a common type of earthworm. However, its toxicity is very low in birds.
Not only can PBO kill living organisms, it can also interfere with the reproduction of many types of wild animals at concentrations much lower than those required for mortality.
On the other hand, PBO is rapidly degraded when exposed to sunlight, with a degradation half-life of about one day compared with 14 days in soil without light.
There is less information available on the persistence of PBO inside homes, but one study found that it persisted for at least two weeks on toys and in dust after a cockroach treatment.|59]
Notes et documents sur le Piperonyl Butoxide (PBO)
- Cox, Caroline. 2002. Insecticide Synergist Factsheet: Piperonyl Butoxide. Journal of Pesticide Reform. 22: 12-20. (accessed Jan 2006)
- US Dept. of Health & Human Services: Agency for Toxic Substances & Diseases Registry. Sept. 2003. Toxicological Profile for Pyrethrins and Pyrethroids. (accessed Jan 2006)
- National Pesticide Telecommunications Network (NPTN). 2000. "Piperonyl Butoxide: Technical Fact Sheet." (accessed Jan 2006)
- US EPA. 2005. "Overview of the Piperonyl Butoxide Risk Assessments." Docket ID EPA-HQ-OPP-2005-0042 p.2 (accessed Jan 2006)
- US EPA/OPP Chemical Ingredients Database. Piperonyl Butoxide. (accessed Jan 2006).
- Whyatt, R.M. 2002. Residential pesticide use during pregnancy among a cohort of urban minority women. Environ. Health Persp. 110: 507- 514.
- Centers for Disease Control (CDC). 2005. Third National Report on Human Exposure to Environmental Chemicals. [https://www.cdc.gov/exposurereport/] (Accessed February 24, 2006).
- PAN Pesticides Database. CAS#51-03-6: Piperonyl Butoxide. (accessed Jan 2006) www.pesticideinfo.org.
- California Department of Pesticide Regulation. 2002. Summary of Pesticde Use Report Data. Indexed by Chemical. (accessed Jan 2006) www.cdpr.ca.gov.
- US EPA. 2005. "Human Health Risk Assessment." Sec. 188.8.131.52-184.108.40.206. Docket ID EPA-HQ-OPP-2005-0042 p.2 (accessed Jan 2006) https://www.regulations.gov.
- Scott, JG et al. 2000. Inhibition of cytocrome P450 6D1 by alkynylarenes, methylenedioxyarenes, and other substituted aromatics. Pesticide Biochemistry & Physiology. 67: 63-71.
- Keseru, GM. 1999. Piperonyl butoxide-mediated inhibition of cytochrome P450-catalyzed insecticide metabolism: a rational approach. Pesticide Science. 55: 1004-1006.
- Graham, C. 1987. 24-Month dietary toxicity and carcinogenicity study of piperonyl butoxide in the albino rat. Unpublished report No. 81690 from Bio-Research Ltd. Laboratory, Seneville, Quebec, Canada. Submitted to WHO by Piperonyl Butoxide Task Force. In Caroldi, S. Piperonyl Butoxide. First Draft. IPCS INCHEM. (Accessed Jan 2006)
- Breathnach, R. 1998. The safety of piperonyl butoxide. In D.G. Jones, ed. Piperonyl butoxide: The insecticide synergist. San Diego: Academic Press. p. 20.
- Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-310. In Piperonyl Butoxide. National Library of Medicine: Hazardous Substance Database. ( accessed Jan 2006) https://toxnet.nlm.nih.gov.
- Prentiss, Inc. 1998. Material safety data sheet: 655-113 Prentox® piperonyl butoxide technical. (accessed Jan 2006).
- World Health Organization and Food and Agricultural Organization. 1996. Pesticide residues in food Evaluations 1995. [Part II] Toxicological and environmental. Geneva, Switzerland: World Health Organization. Pp. 282. In Cox, Caroline. 2002. Insecticide Synergist Factsheet: Piperonyl Butoxide. Journal of Pesticide Reform. 22: 12-20.
- Bateman, D.N. 2000. Management of pyrethroid exposure. Clin. Toxicol. 38: 107-109. In Cox, Caroline. 2002. Insecticide Synergist Factsheet: Piperonyl Butoxide. Journal of Pesticide Reform. 22: 12-20.
- Breathnach, R. 1998. (Ref. #14).
- World Health Organization and Food and Agricultural Organization. 1996. (Ref. #17).
- Breathnach, R. 1998. (Ref. # 14).
- US EPA. 2005. Human Health Risk Assessment. Sec. 220.127.116.11. Docket ID EPA-HQ-OPP-2005-0042 (accessed Jan 2006)
- Nat'l Cancer Inst. Carcinog. Tech. Rep. Ser. 1979. Bioassay of PBO for possible carcinogenicity. 120: 1-131.
- US EPA. 2005. Human Health Risk Assessment. Sec. 6.1.3 Docket ID EPA-HQ-OPP-2005-0042 (accessed Jan 2006)
- Butler, WH, KL Gabriel, FJ Preiss, TG Osimitz. 1996. Lack of genotoxiciy of piperonyl butoxide. Mutat Res 371: 249-58.
- Beamand, JA, et al. 1996. Lack of effect of piperonyl butoxide on unscheduled DNA synthesis in presision-cut human liver slices. Mutat Resis. 371: 273-82.
- Cox, Caroline. 2002. (Ref. #1); US Dept. of Health & Human Services: Agency for Toxic Substances & Diseases Registry, 2003. (Ref. #1).
- McGregor, PB, et al. 1988. Responses of the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay: III. 72 coded chemicals. Environmental and Molecular Mutagenesis. 12: p.85-154.
- Diel, F. et al. 1999. Pyrethroids and piperonyl butoxide affect human T-lymphocytes in vitro. Toxicol. Lett. 107: 65-74.
- Tanaka, T. et al. 1994. Developmental toxicity evaluation of piperonyl butoxide in CD-1 mice. Toxicol Lett. 71: 123-129.
- Tanaka T. 2003. Reproductive & neurobehavioral effects of piperonyl butoxide administered to mice in the diet. Food Addit Contam 20: 207-14.
- US EPA. 2005. Human Health Risk Assessment. Sec. 1.3-6 Docket ID EPA-HQ-OPP-2005-0042 (accessed Jan 2006)
- Breathnach, R. 1998. (See Ref. #14).
- Breathnach, R. 1998. (See Ref. #14).
- Kakko I, Toimela T, Tahti H. 2000. Piperonyl butoxide potentiates the synaptosome ATPase inhibiting effect of pyrethrin. Chemosphere 40: 301-5.
- Grosman, N, F Diel. 2005. Influence of pyrethroids & piperonyl butoxide on the Ca2+ - ATPase activity of rat brain synaptosomes and leukocyte membranes. Int. Immunopharmacol. 5: 263-70.
- Friedman, M.A. and L. R. Eaton. 1978. Potentiation of methyl mercury toxicity by piperonyl butoxide. Bull. Environ. Contam. Toxicol. 20: 9- 10.
- US EPA. 2005. Human Health Risk Assessment. Sec. 1.2 Docket ID EPA-HQ-OPP-2005-0042 (accessed Jan 2006)
- anaka, T. 1993. Behavioral effects of piperonyl butoxide in male mice. Toxicol. Lett. 69: 155- 161.
- Tanaka, T. 1992. Effects of piperonyl butoxide on F1 generation mice. Toxicol. Lett. 60: 83-90.
- Tanaka 2003 (Ref. # 32).
- Maekawa, A. et al. 1985. Lack of evidence of carcinogenicity of technical-grade piperonyl butoxide in F344 rats: Selective induction of ileocaecal ulcers. Fd. Chem. Toxic. 23: 675-682.
- Fujitani, T., T. Tanaka, Y. Hashimoto, and M. Yoneyama. 1993. Subacute toxicity of piperonyl butoxide in ICR mice. Toxicol. 83: 93-100.
- Fujitani, T., Y. Tada, and M. Yoneyama. 1993. Hepatotoxicity of piperonyl butoxide in male F344 rats. Toxicol. 84: 171-183.
- Takahashi, O. et al. 1994. Chronic toxicity studies of piperonyl butoxide in F344 rats: Induction of hepatocellular carcinoma. Fund. Appl. Pharmacol. 22: 291-303.
- Fujitani, T. et al. 1992. Sub-acute toxicity of piperonyl butoxide in F344 rats. Toxicol. 72: 291- 298.
- Hayes, W.J., Jr., E.R. Laws Jr., (eds.). Handbook of Pesticide Toxicology Volume 1. General Principles. New York, NY: Academic Press, Inc., 1991., p. 341 In Piperonyl Butoxide. National Library of Medicine: Hazardous Substance
- Breathnach, R. 1998 (See Ref. #14).
- Breathnach, R. 1998 (See Ref. #14).
- US EPA. 2005. Environmental Fate and Ecological Risk Assessment. Docket ID EPA-HQ-OPP-2005-0042 p. 5 (accessed Jan 2006)
https://www.regulations.gov; PAN Pesticides Database. CAS#51-03-6: (Ref. #8).
- Osimitz, TG and JF Hobson. 1998. An ecological risk assessment of piperonyl butoxide. In D.G. Jones, ed. Piperonyl butoxide: The Insecticide synergist. San Deigo: Academic Press. p. 122-135.
- Roberts, B.L. and H.W. Dorough. 1984. Relative toxicities of chemicals to the earthworm Eisenia foetida. Environ. Toxicol. Chem. 3: 67- 78. In Cox, Caroline. 2002. Insecticide Synergist Factsheet: Piperonyl Butoxide. Journal of Pesticide Reform. 22: 12-20.
- Osimitz, Hobson. 1998. (Ref. #52).
- Osimitz, Hobson. 1998. (Ref. #52).
- Meylan WM et al; 1999 Environ Toxicol Chem 18: 664-72. In Piperonyl Butoxide. National Library of Medicine: Hazardous Substance Database. (accessed Jan 2006)
- LeBlank, LA, JL. Orlando, KM Kuivila. 2004. Pesticide Concentrations in Water and in Suspended and Bottom Sediments in the New and Alamo Rivers, Salton Sea Watershed, California, April 2003. U.S. Geological Survey. Data Series 104. Sacramento, California. (Accessed Jan 2006).
- Arnold, D.J. The Fate and Behavior of Piperonyl Butoxide in the Environment. In Piperonyl Butoxide: The Insecticide Synergist; Jones, D.G. ; Ed ; Academic: San Diego, CA, 1998. pp.105-119.
- Fischer, A, and T. Eikmann. 1996. Improper use of an insecticide at a kindergarten. Toxicol. Lett. 88: 359-364.
- Tozzi, A. 1998. A Short History of the Development of Piperonyl Butoxide as an Insecticide Synergist. In D.G. Jones, ed. Piperonyl butoxide: The insecticide synergist. San Diego: Academic Press. Pp. 122-135.
- US EPA. 2005. Overview of the Piperonyl Butoxide Risk Assessments. Docket ID EPA-HQ-OPP-2005-0042 (accessed Jan 2006)