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

 

  Kuriyama, SN, CE Talsness, K Grote and I Chahoud. 2005. Developmental exposure to low dose PBDE 99: 1- effects on male fertility and neurobehavior in rat offspring. Environmental Health Perspectives 113:149-154.

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Kuriyama et al. report that rats exposed in the womb to a single low dose of a widespread brominated flame retardant become hyperactive and have decreased sperm counts. The effects are observed at an exposure level within the range that has been found in samples of breast milk from US mothers.

What did they do? Kuriyama et al. force-fed pregnant rats a single dose of PBDE-99 on the sixth day after fertilization, comparing unexposed animals to two treatment groups, one receiving 60 µg/kg body weight and another receiving 300 µg/kg. They included another treatment group that was exposed to a drug, PTU (6-n-propyl-2-thiouracil), known to interfere with thyroid hormone; this group served as a positive control.

Behavioral measurements

 

At two separate stages of development, Kuriyama et al. quantified aspects of the behavior of offspring exposed in the womb, comparing them to unexposed controls and the positive control group.

After the offspring reached adulthood, they also examined the males' reproductive tract.

To quantify activity levels, Kuriyama et al. used automated light sensors that detected when the subject was moving.

To quantify mating behavior, after males reached adulthood they were were caged with a receptive female and videotaped for 20 minutes. This tape was then analyzed.

What did they find?

Midway to puberty,animals exposed in the womb to 300 µg/kg and to PTU were significantly more active than controls.

At puberty (graph to right) both groups exposed to PBDE-99 were hyperactive compared to controls.

Differs signicantly from control @ p<0.05

 

As indicated by the number of counts of movement recorded by the light sensors, animals that received 60 µg/kg and 300 µg/kg were 24% and 27%, respectively, more active than controls. Exposed animals at both doses were also active for a greater portion of the day than controls (increases of 15% and 18%, respectively).

Exposure to PBDE-99 did not alter the pattern of sexual behavior in males once they reached adulthood. It did, however, have an effect on ejaculations. In cages with a responsive female, 50% of control males achieved a second ejaculation, whereas only 39% and 21% (60 µg/kg and 300 µg/kg, respectively) of exposed males did. This effect on males exposed to 300 µg/kg was statistically significant (p < 0.05).

 

The most striking findings in the examination of male reproductive parameters were significant reductions in daily sperm production and sperm count (graph to left). Treatment had no effect on sperm morphology or on serum levels of two hormones, LH and testosterone.

Differs signicantly from control @ p<0.05

What does it mean? This study demonstrates adverse effects of PBDE 99 at the lowest levels yet reported for rodents. The findings of altered behavior are consistent with prior work and with current understanding of the role of thyroid disturbances to proper brain development.

The effects on reproductive parameters reveal a new health endpoint that until now had not been identified as a concern for PBDE exposure. But given the established impact of PBDEs on thyroid function, an effect at some level of exposure should be expected. PBDEs are powerful thyroid mimics, binding with transthryetin more powerfully than thyroid itself. Thyroid signals are known to have a major impact on regulating testicular growth and function. Hypothyroidism in rodents and people has been shown to cause increases in adult testis size and sperm production, because a thyroid signal is involved in shutting down testicular growth. Thus a contaminant like PBDEs that mimic thyroid hormone might logically be expected to have the reverse effect, ie., decreased testicular size and decreased sperm production.

These results are important because exposure to PBDEs is widespread, and at least within the US, at levels within the range used in these experiments. In the article, Kuriyama et al. refer to evidence that the doses they use are roughly 6 to 29 times higher than the highest human exposure cited in a 2002 publication. According to Kuriyama et al.:

  "Due to the increasing levels of PBDEs found in human and biota samples, the present study was conducted to examine the effects of a single low dose of 60µg or 300 µg PBDE 99 / kg bw on gestation day 6 on neurobehavior and male reproductive health in rat offspring. Assuming that fat content in rats is circa de 14% total body weight, the doses used in this study are approximately 6 and 29 times, respectively, higher than the highest level reported by She et al. (72.2 µg/kg fat) in human breast adipose tissue."  

Two publications since the She et al. analysis, however, have revealed much higher total PBDE contamination levels in people in the US. In a meta-analysis of PBDEs in people, Hites (2004) reports:

  "In human blood, milk, and tissues, total PBDE levels have increased exponentially by a factor of ~100 during the last 30 yr; this is a doubling time of ~5 yr. The current PBDE concentrations in people from Europe are ~2 ng/g lipid, but the concentrations in people from the United States are much higher at~35 ng/g lipid.  

The values Hites cites above are median values. As he notes, the highest observed levels exceed 300 ng/g (=300 µg/kg, i.e., just under 5-fold greater than She et al.'s highest level above, and thus just beneath the PBDE 99 exposures used by Kuriyama et al. in these experiments (corrected for fat content as noted above).

A study conducted by the Environmental Working Group, published in 2004, moreover, reported a maximum value in US mothers' breast milk of 200 ng/g for PBDE-99 and over 1000 ng/g for all PBDE congeners combined (graph below). This total PBDE congener level is far above the experimental level used by Kuriyama et al. for PBDE-99.

Evidence suggests that while there are differences in toxicity impacts among PBDE congeners, several, including PBDE-99, alter thyroid function. Currently there is no way to estimate the effect of PBDE mixtures comparable to the techniques used for dioxin-like compounds, known as 'toxic equivalency factors.'

Without 'toxic equivalency' information for PBDEs, gauging how Kuriyama et al.'s doses of the one congener, PBDE 99, compare with real world mixtures won't be possible with accuracy. But the pooled effect of a mixture like those reported by the Environmental Working Group, above, is likely to be much higher than the single effect of PBDE 99.

 

 
   
   

 

 

 

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