Piperonyl butoxide, dangerous or not ?
Presentation of piperonyl butoxide (PBO)
The piperonyl butoxide or pbo that is also known as 5-[2-(2-Butoxyethoxy)ethoxymethyl]-6-propyl-1,3-benzodioxole (chemical form C19-H30-O5) is a synergizer very often used in insecticides.
Always allowed in organic farming, the pbo has for a long time raised a certain controversy.
The hygiene and safety sheet (fds) of this product already has an idea of its pure toxicity.
- R23 r24 r25: toxic by inhalation, contact with the skin and ingestion.
- R40: suspected carcinogenic effect: insufficient evidence.
- R50/53: Very toxic to aquatic organisms, can lead to long-term adverse effects on the aquatic environment.
After many researches in literature, mainly Anglo-Saxon, we managed to find a number of information about piperonyl Butoxide.We deliver them raw as we found them.
Main source pesticides and you vol. 26, No. 1, 2006.
History of Piperonyl Butoxide (PBO)
At the end of the 1930s, American manufacturers of pesticides started looking for a way to increase the power of imported japon pyrethra.
The pbo was synthesized in 1947 by herman wachs from the safrole, raw material of natural origin.
Starting in 1952, the United States launched pbo manufacturing in large quantities .
Since then, it is used as synergizer in most commercial insecticides.
It increases the toxicity of active ingredients, allowing less insecticide to be used while maintaining the efficacy of the final product.
In general, there are between 5 to 10 pbo units for 1 active substance unit.
Active matter can be of synthetic origin such as pyrethrinoids or natural origin such as pyrethrins.
What is a synergizer ?
A synergizer is a chemical added to pesticides to increase the toxicity of active ingredients, making pesticide more fatal. but may also compromise mechanisms for detoxification of non-target species, including humans.
Its action is to slow down the degradation 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 allows to maintain pesticide 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 the pbo kill organisms, but it is known to interfere with the reproduction of many types of wild animals 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 to ten times that of pesticide .
Study of piperonyl butoxide (PBO)
Although the pbo is rarely used alone, most studies examined it separately.
When combined with pyrethrins or other insecticides, the toxic effects of chemicals cannot simply be added. the effects are multiplicative.
Assessing the pbo alone results in limited value. most studies, including the file published in April 2005 by theus environmental protection agency (us epa) fail to address the health effects of the combined pbo. In April 2005, the sword launched a public utility survey on the pbo.
The main concern expressed by the public about this file is that the epa should not assess the pbo alone. Synergistic effects should be assessed with the materials with which it is generally marketed, and mainly in urban areas where it is commonly used.
Pbo is commonly sprayed by municipalities in the context of mosquito control.
Exposure of children to the pbo is of concern because of their particular vulnerability.
Where do we find piperonyl butoxide (PBO) ?
There are currently more than 2,500 pbo-containing insecticides. These include aerosols, repellents, pediculicides (poose killers,) agricultural pesticides or intended for the garden (potager, fruit, lawn, ornamental plants). , mosquito control products, termite treatments, veterinary pesticides and insecticides for human clothing and bedding .
Pbo is one of the most commonly used ingredients in insecticides, according to spa polls.
Is currently in approximately 1,600 registered pest control products. 
On labels, the pbo is sometimes listed as an active ingredient, but can also be considered an inert ingredient and therefore not indicated or indicated under another name.
Piperonyl butoxide (PBO) residues in our diet
Because of its widespread use, the pbo can be found in our environment.
A recent study of pregnant women in northern Manhattan and bronx found pbo in more than 80% of the air samples from the place of residence of these women.
Moreover, pbo residues are regularly found in the diet, especially lettuce, lemons, spinach and tomatoes,  as well as basil, chives, coriander, herbs, mint, pears, peppers, oranges, squash and other fruits and plants. 
Epa states that acute food risk is very low, and is below the acceptable intake limit. 
Piperonyl Butoxide (PBO) and Cancer
Epa classifies piperonylbutoxide in group c (human cancer possible)  but currently, no data proves that it is likely to present a carcinogenic risk to man.
The only information comes from animal studies.
Several studies have shown that the treatment of rats with high-dose pbo causes increased liver cancer and a very slight increase in thyroid cancer. 
Piperonyl butoxide and mutagenic effects
It is generally accepted that the pbo does not have a significant genetic alteration potential. [26-27]
This conclusion is not accepted by all, and some studies have evidence of genetic damage. [28-29]
Piperonyl butoxide and immune system
The pbo weakens the immune system by inhibiting the lymphocytary response (the ability of the body to defend against foreign bodies). 
Piperonyl butoxide and acute toxicity
Studies suggest that by interfering with the metabolism of hormones, pbo can damage mood organs such as thyroid, adrenal glands and hypophysis. 
On short-term studies with laboratory animals the pbo is considered weakly toxic.
- Acute oral dl50 was established at 6.15 g/kg for rat and 2.6 g/kg for mouse.
- Dl 50 inhalation for rat is greater than 5.9 g/kg.
- 50 cutaneous dl is 200 mg/kg for rabbit.
- The lethal dose for a human is 5.15 g / kg .
Note: dl50 = dose that kills half of the population tested.
Symptoms caused by high dose pbo ingestion are nausea, cramps, vomiting and diarrhea. 
Inhalation of large quantities of pbo can cause larmoment, salivation, laborious breathing.  accumulation of fluids in the lungs  ,and can cause respiratory problems such as asthma.
Repeated skin and eye contact showed mild irritation, but does not cause long-term damage. 
Pbo overdoses can lead to instability, coma, convulsions and brain damage in rat .
Most deaths in studies are attributed to bleeding in the digestive system, especially in the large intestine.
Acute exposure in animals also triggered liver problems (foie) , anemia and loss of appetite, as well as disturbances in the kidneys, nasal bleeding, loss of muscle coordination and abdominal pain. 
Piperonyl butoxide and reproductive effects
The main effect of prolonged exposure to pbo on animals is an increase in the weight of the liver, thyroid and kidneys, 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 dog study. 
Piperonyl butoxide and long-term toxicity
It has been shown that the pbo could harm certain functions of reproduction, but at the moment there is 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 a retardation of mental development to 36 months.
Children who were the most exposed (about 4,34 ng/m3 of air) lost 3.9 points on the mental development index compared to those who had lower exposures.
The head of this study said: "This decrease in qi points is similar to that observed in lead exposure.".
Two laboratory studies on rats show that when mothers were exposed to high concentrations of pbo, there was an increase in birth defects and fetal death. 
Rats exposed to pbo during two years of experience showed atrophy of testicles, a decrease in the weight of seminal vesicles, and an increase in the weight of ovaries. 
Piperonyl butoxide and neurotoxicity
Data showed that the pbo interferes with enzymes that maintain sodium and calcium homeostasis in the brain and nervous system which could affect the neuronal response.[36-37]
In addition, it increases neurotoxicity of other components associated with it.
Despite these data, the disease estimates that these neurotoxic effects are light and maintains that the pbo poses no neurological risk. 
Behavioural changes were also observed. in a laboratory experiment, exposed rats have more difficulty sailing in a labyrinth than unexposed rats. exposed rats travel longer distances and more often rotate in the labyrinth. 
It also leads to changes in the olfactory behavior of the progeny of exposed mothers. 
These data show that the pbo has the ability to affect mammal behavior.
Piperonyl butoxide and other chronic effects
Research on rats has shown that the pbo can cause ulcers and intestinal bleeding. 
The various studies frequently experience liver damage and kidney damage. 
They also found that the long-term ingestion of the pbo causes anemia, a decrease in the amount of hemoglobin in the blood and an increase in the blood cholesterol level in the rat and that it could cause larynx damage.
Some reports indicate that it can cause respiratory difficulties, accumulation of fluid in the lungs, nasal bleeding, abdominal swelling, and loss of capacity to coordinate muscle movements.
Piperonyl butoxide and environmental effects
PBO is considered moderately toxic to fish, moderately to highly toxic to invertebrates (including crustaceans and insects), and very toxic to amphibians.
In one study, concentrations below one part per million (ppm) killed water chips, shrimps and oysters.
It is also very toxic for a common type of earthworm. However, its toxicity is very low in birds.
Not only can the pbo kill living organisms but it can also interfere in the reproduction of many types of wild animals at concentrations much lower than those required for mortality.
However, the pbo is rapidly degraded when exposed to the rays of the sun, with a half-life of degradation of about one day to 14 days in the ground without light.
Find out less information about the persistence of the pbo inside the houses, but a study found that it had persisted for at least two weeks on toys and dust after anti-cafard treatment.59]
Notes and documents on piperonyl butoxide
- 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. 220.127.116.11-18.104.22.168. 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. 22.214.171.124. 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)