Herbicide impairs how rats care for newborns.

Oct 03, 2008

Sturtz N, RP Deis, G Jahn, R Duffard and AM Evangelista de Duffard. 2008. Effect of 2,4,-dichlorophenoxyacetic acid on rat maternal behavior. Toxicology 247:73-79.




 In rats, exposure to low doses of the widely used herbicide 2,4-D impairs a mother's care giving to her newborn pups. The poor maternal care was linked to changes in certain chemicals in the brains of the mothers as well as to decreased blood levels of the important reproductive hormone prolactin. This animal study by researchers in Argentina is one of the few to show that an environmental pollutant can alter the way a mother cares for her offspring.

Context

2,4-dichlorophenoxyacetic acid, or 2,4-D for short, is a common herbicide used for more than 60 years to control growth of broadleaf weeds in lawns; conifer tree farms; grass hayfields; pastures; and along fences, highways and railroads. More than 1,500 products contain 2,4-D as the active herbicide ingredient. Due to its low cost, it is the third most widely used herbicide in the U.S. and is the most widely used in the world. Although several European nations and Canada have restricted the use of 2,4-D, the U.S. Environmental Protection agency approved the continued use of this chemical as a herbicide in 2005.

Occupational exposures to 2,4-D are reported to be very high (0.3 to 8 mg/L in the blood) for workers applying the chemical in forestry work. Most commonly, workers absorb the chemical through their skin.

To date, scientific evidence does not indicate that 2,4-D is overtly toxic to animals or humans at environmentally relevant levels (National Pesticide Information Center). The chemical does not appear to increase the risk of cancer or birth defects in humans or animals. However, there is increasing evidence that 2,4-D may be toxic to the nervous system. Previous research studies from the same lab as the current study have shown that 2,4-D alters behavior patterns and levels of certain brain chemicals called neurotransmitters (Bertolozzi et al. 2002; Evangelista de Duffard et al. 1990)

Maternal care encompasses all behaviors of the mother that lead to survival and proper development of the offspring, including providing protection, nutrition and an adequate habitat. Good care creates a safe environment and provides protection against stress and disease in the little ones.

Very few studies have examined the effects of environmental pollutants on maternal care. This study is the first to demonstrate that exposure to an environmental herbicide adversely impacts maternal care.

Prolactin is an important reproductive hormone associated with lactation in mammals and levels of this hormone are elevated throughout nursing. Prolactin is made in the pituitary gland, and its synthesis is regulated by brain neurotransmitters, specifically dopamine, which inhibits the hormone's production.

What did they do?

In this study, the authors exposed new mothers (dams) to 2,4-D via food for up to seven days at levels that are not toxic to the nervous system. The concentrations of 2,4-D tested ranged from 15 to 50 milligrams per kilogram (mg/kg) in the diet per day. In terms of a daily dose to the animals, these levels are roughly 1 to 3 mg daily (although blood concentrations of 2,4-D were not measured in this study).

When the pups were five and seven days old, a set of behavior tests and observations were performed to evaluate the effect of 2,4-D on maternal care. The authors measured the length of time it took for the dam to fetch pups that were removed from the nest, the total time it took to retrieve all eight pups, the amount of time the mother spent on her nest keeping the pups warm and the time spent away from her nest feeding. Finally, the authors measured the amount of time she spent grooming the pups and the length of time the pups nursed.

The authors also measured levels of certain neurotransmitters in the brain and the reproductive hormone prolactin in the blood to determine the mechanism by which 2,4-D affected maternal care.

What did they find?

Important care-giving behaviors were dramatically impaired. Compared to control animals, dams exposed to 2,4-D took longer to retrieve her pups back to the nest, spent less time grooming the pups and spent more time out of the nest compared.

The degree of change in some of these behaviors was related to the amount of 2,4-D fed to the mother, and the response to the lowest concentration tested (15 mg/kg diet) was statistically significant for most measurements. Indeed, the dose-dependent pattern of certain behavior responses suggests that even lower levels of 2,4-D may also impair maternal care.

The authors related these changes in maternal behavior to decreased levels of the endocrine hormone prolactin in the dam. Moreover, levels of neurotransmitters of the dopamine pathway were also elevated in 2,4-D exposed dams. These data fit well together, because higher dopamine levels would lead to lower amounts of prolactin made by the pituitary.

Exposure to 2,4-D did not impair nursing behavior of the mothers. Pups whose mothers were fed 2,4-D grew at a normal rate.

What does it mean?

These data support the hypothesis put forward by the authors that “2,4-D may decrease the motivation to care for the pups, and thereby increase the dams’ activities outside the nest.” Overall, these data suggest that exposure to the pesticide 2,4-D reduces maternal care giving and could impact early development and survival of offspring.

Poor care can lead to problems in the babies, although in this case, precisely what, how and why are beyond the scope of the study. Although the authors did not dwell on the pups' conditions, they do mention there were "posterior developmental, neural and behavioral defects observed in the offspring." Whether these were due to lack of care or possible exposure through milk to the herbicide cannot be determined from this study.

The short-term exposure to 2,4-D significantly altered brain chemicals in the mother rats that are important for many physiological processes, including overall mental health. It is not known whether exposure to 2,4-D affects maternal care or brain chemicals in humans.

The present study tested the effects of this herbicide in the seven days immediately after birth, which would correspond to the first three to six months of typical human breast-feeding. Although, it is unlikely that new mothers would be at high risk for occupational exposure to 2,4-D (most of whom do not return to work immediately following birth), some pregnant and nursing women may be exposed by routine household use of the herbicide.

At this point, parent-offspring interactions are not assessed when government agencies test chemicals for safety. However, given the link found between herbicide exposure and changes in the rodents' basic care giving, the authors suggest they should be. They say "these “cross-generational” effects must be taken into account when evaluating toxicological effects of other extensively used xenobiotics that usually are considered as not producing developmental effects."

Resources

Bortolozzi, A, R Duffard, M Antonelli and AM Evangelista de Duffard. 2002. Increased sensitivity in dopamine D(2)-like brain receptors from 2,4-dichlorophenoxyacetic acid (2,4-D)-exposed and amphetamine-challenged rats. Annals of the New York Academy of Sciences 965:314-323.

Evangelista de Duffard, AM, C Orta and R Duffard. 1990. Behavioral changes in rats fed a diet containing 2,4-dichlorophenoxyacetic butyl ester. Neurotoxicology 11:563-572.

National Pesticide Information Center. National Pesticide Telecommunications Network Factsheet on 2,4-D (PDF).

Wikipedia. 2,4-Dichlorophenoxyacetic acid.

 

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