Markowski, VP, G Zareba, S Stern, C Cox and B Weiss. 2001. Altered Operant Responding for Motor Reinforcement and the Determination of Benchmark Doses Following Perinatal Exposure to Low-Level 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Environmental Health Perspectives 109:621-627.

Markowski et al. demonstrate that even at extraordinarily low levels-- parts per trillion--dioxin can reduce motivation in rats to perform in standard psychological testing. The levels at which these impacts are detected are comparable to background levels in people around the world.

This study is important because it is the first to look for subtle but significant impacts of dioxin on nonsexual behaviors following exposure in the womb to environmentally-relevant contamination levels. The fact that dioxin had clear, adverse effects at this level confirms that standard toxicity testing is wholly inadequate as a means of protecting people against contamination risks. More on low dose impacts...

What did they do?
Markowski et al. exposed pregnant rats to a single dose of dioxin 18 days after fertilization. Four exposure levels were used: 0,20, 60, or 160 nanograms/kilogram (ng/kg) of dioxin. These are extremely low exposure levels. One ng/kg corresponds to one part per trillion. Background levels of human exposure to dioxin are on the order of 10 - 20 ng/kg. Thus these experiments examined dioxin impacts at environmentally relevant levels.

Beginning on or about 77 days after birth, female adult offspring were then used in behavioral experiments. The experiments examined how hard the females were willing to work to obtain access to a running wheel. Many previous behavioral studies of rats had established that rats will work hard for this access.

Methods like this are used by behavioral scientists to study motivation in animals.

Markowski et al. put the rats in an experimental chamber with a running wheel and a lever. When the rats pressed the lever, a brake on the wheel was turned off and the rats could run. The rats quickly learned this behavior, and would rapidly press the lever multiple times to turn off the brake. The final experiments required up to 30 lever presses before the wheel would turn. Rats were trained on this "schedule of reinforcement" for 18 sessions.

Data analysis involved comparing performance of the females as a function of dose delivered to their mothers

What did they find?

Dioxin exposure had a large and significant impact on the rats' behaviors, which Markowski et al. interpret as a decrease in motivation. Exposed rats did not work as hard as the control rats. As a result, they did not gain access to the running wheel as often, nor did they run as much once on.

Exposed rats earned fewer running opportunities than control rats. Markowski et al. estimate that the dose required to produce a 10% change compared to controls is just under 10 ng/kg. This curve was generated using EPA's benchmark dose statistical software. adapted from Markowski et al.

One of the important details of their findings involves the effect of exposure on offspring weight. Animals whose mother were exposed to 60 ng/kg increased in weight more than did controls (0 ng/kg) or 180 ng/kg. This is of interest for two reasons:

• First, it is another example of in utero exposure leading to an increase in adult weight. Weight is hormonally-regulated, yet virtually all the public debate about the growing obesity epidemic in people ignores the possibility that hormone disruption may be a contributing factor. Results like these add plausibility to the hypothesis that in utero disruption of weight regulation may be involved.
• Second, it is another example of non-monotonicity in dose-response curves. These inverted-U dose-response curves challenge some of the basic assumptions of regulatory toxicology.

What does this mean?
According to the authors, "these results suggest reduced responsiveness to environmental contingencies, an effect with extensive implications for many kinds of behaviors, rather than a simple developmental motor deficit."

Their bottom line interpretation is that the exposed rats have experienced a decrease in motivation:

Of greatest import is that these results were obtained with single exposures to dioxin at contamination levels within the range of average, background exposures experienced by people.

These results demonstrate that behavioral endpoints can be extremely sensitive to dioxin exposure. They are consistent with observed decreases in sexual motivation of rats (Mabley et al. 1992b) and increased learning deficits in monkeys (Schantz and Bowman 1989), both following low level dioxin contamination.

What this means is that toxicity testing that doesn't include sophisticated assessments of the impact of low-level exposure on behavior are unlikely to be sufficient for preventing harm in people. Given how rarely tests of this nature are ever done, we are left ignorant of impacts that may be widespread because of the ubiquity of exposure.