Daily Archives: September 5, 2017

Does talcum powder cause ovarian cancer? Weighing up the human and animal studies

In this article, Justin Varholick, investigates the evidence on whether talcum powder can cause ovarian cancer. Over the years, several courts have ruled that talcum powder can cause ovarian cancer, while the scientific evidence suggests otherwise. In light of Ovarian Cancer Month, it is important to highlight how animal and human studies can improve our understanding of the disease, and prevent misinformation spread from the media. This article outlines that both animal and human studies are not perfect. Animal studies sometimes do not have proper controls and human studies suffer from bias. The current research suggests no direct link between talc and cancer, but more research is certainly necessary.

Ovarian cancer is a serious disease affecting around 22,000 women in the United States and contributing to around 14,000 deaths each year. Since the 1960s the American public has questioned whether the use of talcum powder – for soothing dry skin, absorbing sweat, and preventing chafing of the thighs — increases women’s’ risk for ovarian cancer. This speculation began after acknowledging the risks of asbestos and public theories that asbestos was in talc products; however, cosmetic grade talc undergoes strict quality control and does not contain asbestos.

Image by Austin Kirk

Multiple studies on rodents, non-human primates, and humans have investigated the link between talc and cancer since the 1960s. Overall the results are inconsistent; some studies suggest talc is associated with ovarian cancer while others suggest talc is not carcinogenic. Recently, despite these inconsistencies, a Los Angeles jury ordered Johnson & Johnson to pay $417 million to a woman who blamed her terminal ovarian cancer on the use of baby powder — this is just one of many lawsuits against Johnson & Johnson over their talc powder. In light of this recent event I would like to delve into the animal and human studies investigating the link between talcum powder and ovarian cancer.

Is talcum powder a carcinogen?

Empirical studies first began on rodents such as hamsters, rats, and mice; however, these studies only focused on whether talc was a carcinogen in general. Researchers chose rodents because it is relatively easy to systematically administer talc to rodents via inhalation. Furthermore, rodents — especially the laboratory rat — are particularly sensitive to forming malignant tumors in the lungs when exposed to chemicals via inhalation regardless of the chemical itself. Therefore, by using rodents there is an increased chance of detecting an effect of cancer following exposure to talc via inhalation — if one is present. It is important to note here that although humans are exposed to talc by inhalation or via topical application, the specific method of applying talc is not important when determining general carcinogenicity.

For one of the first studies investigating talc exposure and cancer in rodents, researchers first gathered information on how much baby powder human infants were regularly exposed to – although infants are usually exposed via topical application and rodents are exposed via inhalation. Using this information they designed an experiment using hamsters and exceeded the amount of talc human infants are normally exposed to by 30 to 1700 times — depending on the experimental treatment group. The scientists also formed a control group that was exposed to a negative dust control; titanium dioxide. This control is important because increased levels of dust in the air can lead to chronic inflammation of the lungs, which increases the risk of malignant tumors — independent of particle type (e.g. talc powder, titanium dioxide, toner, carbon black, etc.). Controlling for dust and exceeding levels of normal exposure, the study reported no difference between the groups in body weight, survival, or signs of cancer in the larynx, trachea, lungs, liver, kidney, stomach, uterus, ovaries, or testes of these hamsters.

Further studies were conducted on rodents — specifically mice and rats — that did find an effect linking cancer to talc; however, these studies were confounded. One study in particular found that female rats and mice exposed to high levels of talc via inhalation for 4 months had a higher risk of lung cancer. Unfortunately, this study did not use a titanium dioxide control group, thus the finding could be an artefact of chronic inflammation from air particles — as discussed above. Furthermore, this study was unable to identify another biological mechanism beyond chronic inflammation responsible for the onset of cancer.

In summary, these rodent studies allowed scientists to exceed normal exposure levels and use an animal with increased sensitivity to the treatment in question. However, proper control groups must be used to help elucidate whether the effect is an artefact. Importantly, these studies were only interested in whether talc is a possible carcinogen, not whether ovaries exposed to talc have increased risk of cancer specifically. Overall, these studies were unable to find a link between talc and risk of cancer, beyond chronic inflammation from increased levels of air particulates.

Can talcum powder be found in the ovaries?

Some studies in animals and humans have been particularly focused on finding a link between talc use and ovarian cancer — not just whether talc is a carcinogen. To understand the plausibility of this link, these studies first needed to establish whether it is possible for particles of talc to migrate into the genital tract after being applied topically to the perineal region (area between vagina/scrotum and anus). A simple understanding of biophysics led many to conclude that it was impossible for the particles to travel up the vagina, cross the cervix, travel through the uterus, and then “swim” upstream through the oviducts; without being assisted by some form of locomotion. Nonetheless, some studies using animals investigated whether it was a possibility. Specifically, one study using female cynomolgus monkeys (Macaca fascicularis) — an animal model anatomically and physiologically comparable to human female — investigated whether carbon black particles could reach the oviducts or ovaries. This study was unable to conclude that carbon black particles could indeed travel up to the oviducts or ovaries.

Image by Noveprim

Further studies were done with human females that applied talcum powder to their underwear or perineal region daily that also had ovarian or pelvic cancer; which required surgical removal of the ovaries.  After removing the ovaries, scientists used microscopy techniques to scan the ovaries and identified low numbers of particles that were relatively small in size in about 50–75% of cases (multiple studies). Thus, although talc can be found in or around ovarian tissue the amount found was considered too small to cause ovarian cancer. It has also been noted that findings from these studies were widely inconsistent and were confounded by women lying in a supine or Trendelenburg position — which may aid in the surgery of the pelvic region but is also used to aid in vitro fertilization.

Thus, studies in both animals and humans cannot definitively suggest talc can translocate from the perineal region to the ovaries, which may be necessary for the talc to affect the ovaries. Nonetheless, both animal and human studies have been limiting; studies with monkeys only used a particle similar to talc and human studies involved a lying position that aided in the migration of talc up the genital tract.

How many women using talcum powder get ovarian cancer?

Two types of human studies have investigated, and continue to investigate, the link between talc and ovarian cancer; case-control and cohort studies. The case-control studies gather a group of women diagnosed with ovarian cancer and a group of women with no ovarian cancer. They then ask all women to retrospectively discuss their use of talc on the genital area throughout their life — noting frequency and average amount. The obvious downside to this type of study is that it is open to reporting bias. Some women may forget when or how often they used talc, while others may overestimate their use and further bias may occur if there is an expectancy that talc may have contributed to the onset of ovarian cancer. In contrast, the cohort studies gather a group of women early in life and then have them report in real-time throughout their life how often they use multiple products — including products with talc. After several decades they then compare how many women are diagnosed with ovarian cancer and used talc products, diagnosed with ovarian cancer and did not use talc products, etc. Cohort studies, however, are often limiting because few women are actually diagnosed with ovarian cancer compared to those that are not.

A recent meta-analysis, published this year, gathered 24 case-control and 3 cohort studies investigating the use of talc on the perineal region and its relation to ovarian cancer. Gathering all of these studies into a single analysis, they found that talc powder use on the perineal region is associated with a small increased risk of developing ovarian cancer; however, case-control studies largely contributed to this association — which have obvious disadvantages as outlined above. This positive association was also limited to a single type of ovarian cancer; identified as serous carcinoma — the most common type of ovarian cancer (types of ovarian cancer). Importantly, if reporting bias is affecting the case-control studies, then the association between talc use and ovarian cancer should not be limited to a single type of ovarian cancer. The authors also note that publication bias may also be affecting the case-control studies, meaning that some hospitals may gather information about talc use and ovarian cancer but do not publish their findings because they do not find a link between the two.

In summary, studies with humans do suggest that there is a small positive association between talc use and ovarian cancer; however, these studies are largely limited to case-control studies which have disadvantages of reporting and publication biases. Furthermore, these studies can only tell us about the relative risk of ovarian cancer when using talc. They cannot tell us about the biological basis linking talcum powder use to cancer.

Talcum powder does not cause ovarian cancer

The current evidence from both animal and human studies does not suggest that talc can be directly linked to ovarian cancer. However, both animal and human studies are not perfect. Studies using animals sometimes lack important controls and are not able to properly investigate the specific question at hand without proper animal models (i.e. cynomolgus monkeys). However, animals can be utilized in investigating whether talc is a carcinogen in general because some are especially sensitive to different types of treatments. Studies with humans also have disadvantages due to limitations of subject pools and biases. Despite this, studies with humans somewhat consistently find a link between talc and ovarian cancer, thus humans may be particularly sensitive to talc beyond other animals — although this is highly unlikely given that studies on other mammals suggest no direct relationship.

Importantly, there are many more studies on animals and humans that investigate the link between talc and cancer that I did not include in this brief discussion. Therefore, it is important to note that in a recent review in 2015, the Cosmetic Ingredient Review Expert Panel reported that talc is safe to use in standard practices with normal concentrations. They also note that there is:

  • Absence of persuasive evidence that talc can migrate from the perineum to the ovaries
  • Lack of consistent statistically significant positive associations across studies
  • Failure to rule out plausible alternative explanations of statistically significant results, including biases, risk factors, and exposure to misclassifications
  • Absence of a plausible biological mechanism
  • Lack of credible, defensible evidence of carcinogenicity from results of epidemiological studies of occupational exposures and animal bioassays

Thus, more research is necessary to determine whether talc is linked to ovarian cancer, despite what the Los Angeles courts might say.

Justin Varholick

 

References

Berge, W., Mundt, K., Luu, H. and Boffetta, P. 2017. Genital use of talc and risk of ovarian cancer: a meta-analysis. European Journal of Cancer Prevention.

Fiume, M.M., Boyer, I., Bergfeld, W.F., Belsito, D.V., Hill, R.A., Klaassen, C.D., Liebler, D.C., Marks, J.G., Shank, R.C., Slaga, T.J., Snyder, P.W. and Andersen, F.A. 2015. Safety assessment of talc as used in cosmetics. International journal of toxicology 34(1 Suppl), p. 66S–129S.

Reid, B.M., Permuth, J.B. and Sellers, T.A. 2017. Epidemiology of ovarian cancer: a review. Cancer biology & medicine 14(1), pp. 9–32.

Wehner, A.P. 2002. Cosmetic talc should not be listed as a carcinogen: comments on NTP’s deliberations to list talc as a carcinogen. Regulatory Toxicology and Pharmacology 36(1), pp. 40–50.