Our Stolen Futurea book by Theo Colborn, Dianne Dumanoski, and John Peterson Myers
 
 

 

  Palanza, P, KL Howdeshell, S Parmigiani and FS vom Saal. 2002. Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice. Environmental Health Perspectives 110 (suppl 3): 415-422.

The EPA currently considers an exposure to 50 µg/kg/day (50 ppb) of bisphenol A to be safe (what EPA calls the 'reference dose'). This standard is based upon an evaluation of prior studies conducted in the 1980s in which the lowest dose at which an adverse effect (called the LOAEL) was seen was 50 mg/kg/day.

Palanza et al. show that exposures to 1/5th the level considered safe are sufficient to alter maternal behavior in mice, including reductions in time spent nursing, increases in time resting away from offspring, and increases in time spent out of the nest. Their study adds to the growing weight of evidence that current health standards for bisphenol A need to be strengthened dramatically. If a new 'safe level' were based on this study, with safety factors comparable to the current approach, the new 'reference dose' would by 5,000 times lower than today's standard, or 10 ng/kg/day (10 parts per trillion).

Under these circumstances, it is unlikely that BPA could be used in any products that come in contact with food or water. Because BPA leaches from landfills into water supplies,it is also likely that major changes would be required in water filtration methods.

What did they do? Palanza et al. exposed female mice to BPA and measured several different characteristics of maternal behavior. Some of the mice were exposed while in the womb, by feeding their pregnant mothers. Another set was exposed only in adulthood, while lactating. A third set was exposed both in the womb and in adulthood. The exposure level used was 10 µg/kg/day, one-fifth the current reference dose, delivered in a corn oil mixture.

Exposure in the womb took place on gestational days 14-18, a period during which the fetal brain and urogenital system are differentiating.

Lactating mothers were observed for 120 minutes during days 2-15 after giving birth. During the observation period, the mother's behavior was categorized once every 4 minutes. The categories were: (1) in nest; (2) nursing; (3) licking pups; (4) nest building; (5) eating/drinking; (6) self-grooming; (7) active (moving about cage); (8) resting; (9) forced nursing.

What did they find? Maternal behavior was altered in a number of ways. Females that were exposed to BPA only as fetuses or only as adult dams in late pregnancy exhibited lower levels of nursing behavior toward their offspring and higher amounts of
behaviors outside the nest (active, resting, and self-grooming). In most measurements, females exposed both in the womb and lactationally did not differ from controls.

 

For example, females exposed either in the womb or while lactating spent less time nursing their offspring. Females exposed at both times did not differ from controls.

From Palanza et al. 2002. * indicates significantly different from control at p< 0.05

In these graphs, oil-oil denotes animals never exposed to BPA (controls). BPA-Oil denotes animals exposed in the womb but not while lactating. Oil-BPA indicates exposure only while lactating. BPA-BPA indicates exposure during both periods.
The same two groups of females also engaged in more nest building, compared to controls.  
  For one measurement, % observations spent resting alone, all treated groups differed from controls.
Of all the variables measured, the only one for which exposed animals did not differ from controls was the % observations eating.  

What does it mean? These results demonstrate that BPA at extremely low doses alters neuroendocrine systems in ways that lead to changes in maternal behavior.

Does this matter? From the point of view of the mouse, Palanza et al. consider the observed impacts to be adverse. While they reported they saw no differences in weights of the pups or in neurobehavioral development resulting from the altered maternal behavior, other experiments with animals have shown long-lasting influences of maternal behaviors in shaping brain development and function in offspring. For example, maternal behavior can alter gene expression in her offspring in ways that change how they respond in adulthood to stress.

From the point of view of regulatory standards at EPA, this study reinforces concerns about whether today's BPA standards are sufficient to protect public health. The dose used in the experiment was 1/5th the level EPA had determined to be the reference dose for BPA, itself 1000-fold below the accepted LOAEL, which had been determined in the 1980s. As noted in the introductory comments, a new standard using these experiments to establish a LOAEL would severely constrain the use of BPA in today's economy.

More generally, these results challenge a regulatory assessment framework that ignores low-dose testing. The effects reported by Palanza et al. are not the traditional endpoints of toxicity testing, which emphasize cell death, mutagenicity, carcinogencity, etc., i.e., outright signs of toxicity. These effects are likely to have been mediated by BPA-induced changes in gene expression. As scientists explore this new realm of functional toxicology, they are discovering adverse effects in many unexpected places, from compounds like BPA that traditional testing had deemed benign, affecting a wide range of endpoints.

 

 
   
   

 

 

 

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