A common chemical found in household and agricultural insecticides may raise the risk of a rare birth defect, a study has suggested.
Piperonyl butoxide, often shortened down to PBO, was linked to holoprosencephaly (HPE) in a study on mice.
Scientists have warned they cannot prove the same would happen in humans – but called for further trials on PBO to confirm its effects.
PBO is widely used in insecticides for house plants, as well as in mosquito repellents and head lice shampoos.
Few studies have been done on the chemical – but it is considered safe by official boards because it is unlikely to be absorbed by the body.
University of Wisconsin-Madison researchers found that PBO interferes with the so-called sonic hedgehog pathway.
The pathway is critical for early development, and disruption in signals can lead to severe developmental abnormalities in the brain, lungs and skeleton.
Female mice given a dose of PBO had offspring with stunted brain development and distinct facial abnormalities.
Piperonyl butoxide, often shortened down to PBO, was linked to holoprosencephaly (HPE) in a study on mice
The study, led by Robert Lipinski, a professor of comparative biosciences, has been published in the journal Environmental Health Perspectives.
Professor Lipinski said: ‘We don’t know if PBO is contributing to birth defects in the human population.
‘But our study suggests that more rigorous examination of PBO’s potential human health effects is warranted.’
HPE is exhibited in a range of developmental abnormalities, ranging from cleft lip and palate, to far more serious malformations.
In humans, live births with HPE are very rare, occurring in roughly one in 10,000 newborns.
However, it is believed to affect as many as one in 250 human embryos, most of which never make it to term.
There is very likely a genetic component to the condition as well, with at least 12 genes known to be linked with HPE.
Current studies indicate the vast majority of infants with HPE do not survive past the first six months of life.
PBO was first synthesized in the 1940s and is an ingredient in at least 2,500 pesticide products, according to the Environmental Protection Agency (EPA).
WHAT IS HOLOPROSENCEPHALY?
Holoprosencephaly is an abnormality of brain development in which the brain doesn’t properly divide into the right and left hemispheres.
The condition can also impair the development of the head and face.
There are four types of holoprosencephaly, distinguished by severity. From most to least severe, the types are alobar, semi-lobar, lobar, and middle interhemispheric variant.
The cause of HPE is unknown. Often, no specific cause can be identified.
It is estimated that HPE affects one in 5,000-10,000 live births.
Since many pregnancies with an affected foetus’ end in early miscarriage, the frequency among all pregnancies may be as high as one in 200-250.
Given the known poor prognosis, women are offered a choice of continuing with the pregnancy with the support of the hospital team, or termination of the pregnancy.
Some women may choose to terminate the pregnancy.
For those who choose to continue, treatment is based on management of the condition of the baby and support for the parents.
Current studies indicate that only three per cent of all foetuses with HPE survive to delivery and the vast majority of these infants do not survive past the first six months of life.
Sources: NHS and National Center for Advancing Transnational Sciences
It is not designed to kill insects by itself, but enhance the shelf life of an insecticide and reduce the amount of actual insecticide in the product.
PBO was identified in 2012 as an inhibitor of the sonic hedgehog signalling pathway, which is present in animals ranging from fruit flies to mice and humans.
The signalling pathway is involved in multiple aspects of embryonic development, including the brain and face.
Professor Lipinski and his colleagues built on these findings by showing how PBO can effect early development in mice.
They exposed pregnant mice to dose of PBO at a critical stage of development, when the female mouse was eight days pregnant.
All of the offspring had defects in the structures of their forebrain. The severely affected offspring had what would be diagnosed as HPE.
The baby mice also had hypoplasia, which is when the upper jaw, cheekbones and eye sockets have not grown as much as the rest of the face, as well as hypotelorism, when the eyes are very close together.
Profesor Lipinksi said: ‘This is all about timing. The critical period is very early in development.’
The authors wrote: ‘Human exposure to PBO and its potential contribution to etiologically complex birth defects should be rigorously examined.’
The team also studied how strongly the sonic hedgehog pathway was inhibited in mouse and human cells in the lab.
A previous study of household dust found PBO to be a ‘top 10’ common chemical contaminant, indicating its abundance in the environment.
A 2002 study found PBO in 75 per cent of air samples provided by pregnant women.
But Professor Lipinski said: ‘It’s been said that birth defects like holoprosencephaly are caused by “a little bit of this and a little bit of that”.’
PBO’s influence on human health has been the subject of relatively little scientific scrutiny, with only a handful of published studies.
At present, labels of products containing PBO provide no cautionary information for exposure during pregnancy.
WHAT IS PIPERONYL BUTOXIDE?
Piperonyl butoxide (PBO) is one of the most commonly used synergists in pesticide products.
Synergists are chemicals added to pesticide formulations to enhance the toxicity of the active ingredients.
It may be used in mosquito sprays, lice killers, pesticides on pets and insecticides for human’s clothing or bedding.
According to surveys by the Environmental Protection Agency (EPA), PBO is one of the most commonly used ingredients in insecticides.
It is currently found in approximately 1,600 to 1,700 registered pest control products.
But EPA claims that dietary food risk – from residue on fruits and vegetables – is very low. The body doesn’t appear to absorb much PBO.
Short term exposure caused by ingestion of PBO in large doses can cause symptoms of nausea, cramps, vomiting, and diarrhea.
Long-term exposure to PBO in animal studies has shown an increase in liver and thyroid weight, liver and kidney damage, and weight loss.
Based on some studies, EPA has classified PBO as a possible human carcinogen.
However, the Internal Agency for Research on Cancer (IARC) evaluated PBO and reported that it is ‘not classifiable as to its carcinogenicity to humans.’