“Everyday chemicals linked to miscarriage and birth defects,” The Daily Telegraph reported.
Its story is based on a study of the possible effects of bisphenol A (BPA) on the reproductive development of female monkey foetuses. BPA is a chemical commonly found in food containers and water bottles and is used in the manufacture of plastics.
Researchers found that some forms of exposure to BPA were associated with changes in the development of egg cells within the ovaries of the female monkey foetuses.
This animal study adds to the body of research on the safety of BPA, which is a common chemical that has been in the spotlight in recent years. Previous research in mice has suggested that BPA caused similar effects as well as disrupting infant development. It is also known that BPA can block or interfere with the actions of certain hormones.
BPA has been banned from plastic baby bottles in the EU and Canada as a precautionary measure.
It’s worth noting that while previous studies have been carried out in rodents, this study was undertaken in primates, which are closer to humans in their development and characteristics. As such, its results will be of concern to scientists involved in food safety. However, the study researchers say they ran up against some technical difficulties, meaning their results are not complete.
Critics of the research, as quoted by the Telegraph, argue that the levels of BPA used by the researchers in this, and similar studies, are much higher than the levels humans would normally be exposed to.
The study does not show that the chemical is linked to miscarriage and other birth defects in humans, as implied by the Telegraph.
European Food Safety Authority review
In April this year, The European Food Safety Authority (EFSA) started work on a new risk assessment of BPA, focusing in particular on exposure in vulnerable groups such as pregnant women and infants. The EFSA is to review all available data and scientific studies on dietary and non-dietary exposure to BPA published since 2006 and will evaluate uncertainties about the possible relevance of animal studies to human health. At the moment, the tolerable daily intake for BPA is set at 0.05mg/kg body weight, with exposure in humans currently estimated to be well below this limit.
Where did the story come from?
The study was carried out by researchers from Washington State University and the University of California and was funded by the National Institute of Environmental Health Sciences and other academic institutions.
The study was published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences (PNAS).
The results of this laboratory study were exaggerated by the Telegraph, which claimed that the research showed BPA could “cause women to miscarry and birth defects in their grandchildren”. The study looked at monkeys not humans and, even in monkeys, it did not look at any association between BPA and miscarriage or birth defects.
Nevertheless, researchers say their results could suggest that the implications for humans are “troubling” because the impact of these effects “would not be manifested for a generation”.
Also, the fact that BPA is so widely used in the modern world (an estimated 2 million tons are produced every year) means that any potential health risks associated with human exposure need to be taken very seriously.
What kind of research was this?
This was an animal study that aimed to look at the effects of BPA on the developing ovary in rhesus monkey foetuses. A female is born with all the egg cells she will ever have, and these are immature egg cells surrounded by follicles. This study examined the impact of BPA exposure on the development of these egg cells in the foetal ovary. The researchers point out that previous studies in rodents have reported that low dose exposure to BPA adversely affects two distinct stages of reproductive development in the foetal ovary:
- an early stage, when chromosomal changes result in the development of separate egg cells (ova)
- a later stage when follicles are formed in the ovary (follicles are the ‘package’ of cells that surround and protect the egg cell)
This study set out to investigate whether similar disturbances took place in monkeys (specifically rhesus monkeys, which share many biological similarities with humans).
The researchers say that BPA, a synthetic chemical, is in widespread use in consumer products and that it has endocrine (hormone) disrupting properties. During the past 15 years, adverse effects have been reported on low-dose exposures in hundreds of experimental studies and some human ones, they say.
What did the research involve?
The researchers used adult female monkeys who were pregnant with female foetuses. One group of pregnant females was given a single daily oral dose of chemically modified BPA in small pieces of fruit containing 400µg BPA per kg body weight. A second group of females received continuous BPA through controlled release implants (placed under the mother’s skin) designed to produce sustained low level exposure to the chemical (levels of 2.2 to 3.3ng/ml). This was an attempt to account for possible variation in human exposure to BPA. The researchers suggest it is possible that not all BPA exposure is through food.
There is a great deal of uncertainty about how much BPA humans are exposed to as a consequence of modern living.
Two control groups of pregnant monkeys that received no BPA were also included in the study.
Each of the groups was further divided into early and late treatment groups. Members of the early exposure group were given BPA at between 50 and 100 days of pregnancy. This is during the second trimester, when early cell differentiation occurs in the reproductive system. The late exposure group were given BPA from 100 days into the pregnancy until full term, when the formation of ovarian follicles normally takes place. In all groups, levels of BPA in the adult female’s blood were measured at the time the foetal ovaries were examined.
Researchers removed all foetuses by caesarean section at the end of each treatment period. Using specialised laboratory techniques they analysed the development of the cells of the foetal ovaries and recorded any defects in each group and in control groups. The scoring was carried out by observers who were “blinded” to the status of individual monkeys.
What were the basic results?
Early treatment group – exposure in food
The researchers say that for the “early” group who were given daily oral doses of BPA during the second trimester of pregnancy, in one chemical test, technical difficulties in the preparation of slides meant that the results were not available for all groups across all tests.
This meant that the “limited data” they had – from two BPA-exposed monkeys and one control – “precluded meaningful analysis”. That is, the sample size was too small to compare differences in egg cell development between the exposed and unexposed monkeys.
In other tests of chromosome and cell development, among monkeys given a daily oral dose, there was no obvious difference between the foetuses from monkeys exposed to BPA and the control group.
Early treatment group – continuous exposure through BPA implant
Foetuses of monkeys in the early treatment group that were continuously exposed to low-levels of BPA had certain abnormal cell changes compared with the control group.
The researchers concluded that for the animals exposed continuously to BPA via implants, chemical analysis suggested that BPA was associated with “subtle disturbances” in the very early stage of egg cell development.
Late treatment group – exposure in food
Among the monkeys given an oral daily dose of BPA during the third trimester of pregnancy, foetuses were found to have an increase in the number of abnormal “multioocyte follicles” – that is, follicles with more than one egg cell – than the control group. This was similar to results reported in rodents.
Late treatment group – continuous exposure through BPA implant
Among the foetuses taken from monkeys who were continuously exposed to BPA during this period, researchers found no significant difference between the exposed and control groups in terms of the number of eggs per follicle. They report, however, that there was a marked increase in both small immature egg cells unenclosed by follicles and also an increase in “small, nongrowing” immature egg cells, compared with the control group.
How did the researchers interpret the results?
The researchers say the results from their study show that BPA disrupts key events in the early stage of reproductive development and the later stage of follicle formation in rhesus monkeys, and that their results are similar to the results from studies in mice. They say that this raises concerns for the effect of BPA on human reproductive health. All these effects were found using doses that result in circulating levels of BPA similar to those reported in humans, they say, raising concerns for the effects of BPA on human reproductive health. Though some experts have commented that they believe that this is an assumption on the part of the researchers rather than a (current) provable statement of fact.
This animal study of a small number of monkeys adds to the body of research on the safety of BPA, and its results will no doubt be analysed further by scientists involved in the safety of food products.
The UK Food Standards Agency advice at present is that levels of BPA found in food are not considered harmful. The agency says that independent experts have worked out how much BPA we can consume over a lifetime without coming to any harm, and that the amount absorbed from food and drink is significantly below this level.
Independent studies have found that even when consumed at high levels, BPA is rapidly absorbed, detoxified and eliminated from the body, and is, therefore, not a health concern.
It should be noted that while it was reported that blood levels of BPA were similar to those reported in human studies, most of the significant differences between the exposed and unexposed control groups were found among monkeys who had been given an implant that had exposed them to continuous low-level doses of BPA. This administration route appears to have been introduced because, to achieve circulating BPA levels similar to those reportedly seen in blood samples from pregnant women, oral doses of eight times the current FDA ‘safe dose’ were required.
The researchers interpreted this to mean that human exposure to BPA occurs at significantly higher levels and through routes other than food, but this theory needs further investigation.
The claim in The Daily Telegraph that this research shows a ‘link’ between exposure to BPA and an increased risk of miscarriage and birth defects cannot be supported by this research. Neither miscarriage nor birth defects were investigated in the research.
But the fact that the researchers did find changes in the development of egg cells within female monkey foetuses, at key stages of cell development, does raise a number of worrying implications that require further investigation.
This research will need to be considered in combination with other BPA studies and forms part of the evidence for the debate surrounding the safety of BPA exposure.
- Hunt PA, Lawson C, Gieske M, et al. Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey. PNAS. Published online September 24 2012