Behavioral responses of rats exposed to long-term dietary vinclozolin
Abstract
Vinclozolin is a fungicide used on food crops with human exposure estimated at approximately 2 microg/kg/day from ingestion; occupational exposure, however, may be greater. The metabolites of vinclozolin have been reported to act as antiandrogens and have adverse effects on reproductive physiology and behavior in animals. Here, pregnant rats were fed soy-free diets containing 0, 10, 150, or 750 ppm of vinclozolin (approximately 0, 0.8, 12, and 60 mg/kg/day for an adult) beginning on gestational day 7, and offspring were continued on these diets through sacrifice at postnatal day 77. Male and female offspring were assessed for changes in several nonreproductive sexually dimorphic behaviors: open field and running wheel locomotor activity, play behavior, and consumption of saccharin- and sodium chloride-flavored solutions. There was a significant interaction of sex with vinclozolin exposure on running wheel activity, which indicated that females in the high-dose exposure group were hypoactive compared to same-sex controls. There was a significant overall effect of vinclozolin exposure on fluid consumption, and high-dose animals showed increased intake of the saccharin solution and decreased intake of plain water while saccharin was available. Effects were more pronounced in females, which drank 40.8% more saccharin than control females, whereas males drank 6.2% more than control males. There were no effects of vinclozolin treatment on play behavior or sodium solution intake. Ge…
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In both Flynn et al. (2001) and Gray and Ostby (1998) studies, no effect of perinatal vinclozolin was found on male play behavior.
“In both of these studies, no effect of perinatal vinclo- zolin was found on male play behavior.”
From Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat. (2002) · cites this paper as Flynn et al. 2001
In studies by Flynn et al. (2001) and Gray and Ostby (1998), neonatal exposure to the AR antagonist was through lactational exposure, whereas in Hotchkiss et al. (2001) the compound was administered directly to the pup.
“First, in studies conducted by Flynn et al. (2001) and Gray and Ostby (1998), neonatal exposure to the AR antagonist was through lactational exposure. In the Hotchkiss et al. study (2001), the compound was administered directly to the pup.”
From Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat. (2002) · cites this paper as Flynn et al. 2001
The dose used in the Flynn study was lower (up to 60 mg/kg/day to pregnant female) than that used in the Hotchkiss et al. (200 mg/kg/day to neonatal pup) and Gray and Ostby studies (200 mg/kg/day to pregnant female).
“Second, the dose used in the Flynn study was lower (up to 60 mg/kg/day to pregnant female) than that used in the Hotchkiss et al. (200 mg/kg/day to neonatal pup) and Gray and Ostby studies (200 mg/kg/day to pregnant female).”
From Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat. (2002) · cites this paper as Flynn et al. 2001
One study using chronic low-level dietary exposure to Vz found that female rats were more sensitive than males.
“One study that used a chronic, low-level dietary exposure to Vz found that female rats were more sensitive than males (Flynn et al. 2001).”
From Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat (2005) · cites this paper as Flynn et al. 2001
Cites
The psychobiology of play: Theoretical and methodological perspectives
Panksepp, J., Siviy, S., & Normansell, L. (1984) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(84)90005-8 · Cited by 468 · see citing works
Effects of genistein exposure on sexually dimorphic behaviors in rats.
Flynn, K. M. (2000) · Toxicological Sciences · doi:10.1093/toxsci/55.2.311 · Cited by 92 · see citing works
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Hotchkiss, A. K., Ostby, J. S., Vandenburgh, J. G., & Gray, L. E. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.02110s3435 · Cited by 82 · see citing works
“Several other reports have recently investigated the potential effect of antiandrogens on behavioral development in the rat (Flynn et al. 2001; Gray and Ostby 1998).”
BackgroundResultColbert, N. K. W., Pelletier, N. C., Cote, J. M., Concannon, J. B., Jurdak, N. A., Minott, S. B., & Markowski, V. P. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7509 · Cited by 60 · see citing works
“One study that used a chronic, low-level dietary exposure to Vz found that female rats were more sensitive than males (Flynn et al. 2001).”
BackgroundResultInfluentialFerguson, S. A., Law, C. D., & Kissling, G. E. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu077 · Cited by 32 · see citing works
Self-citationBlake, B. E., & McCoy, K. A. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.04.021 · Cited by 20 · see citing works
Pinning in the Play Fighting of Rats: A Comparative Perspective With Methodological Recommendations
Himmler, S. M., Himmler, B. T., Stryjek, R., Modlińska, K., Pisula, W., & Pellis, S. M. (2016) · International Journal of Comparative Psychology · doi:10.46867/ijcp.2016.29.00.06 · Cited by 19 · see citing works
Dias, G. R. M., Giusti, F. C. V., de Novais, C. O., de Oliveira, M. A. L., Paiva, A. G., Kalil-Cutti, B., Mahoney, M. M., & Graceli, J. B. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1571689 · Cited by 14 · see citing works
- Authors
- Flynn, K. M., Delclos, K. B., Newbold, R. R., & Ferguson, S. A.
- Affiliations
- National Center for Toxicological Research (US)
- Venue
- Journal of Agricultural and Food Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2001-03-01
- Volume
- 49
- Issue
- 3
- Pages
- 1658-1665
- ISSN
- 0021-8561 (ISSN-L)
- 1520-5118
- OpenAlex
- W1979416247
- Cited by
- 33
- References
- 2
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Agricultural and Food Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- vinclozolin, fungicide exposure, developmental toxicity, sexually dimorphic behavior, locomotor activity, wheel running, saccharin consumption, fluid intake, play behavior, offspring behavior, prenatal exposure, sex differences
- MeSH terms
- Administration, Oral, Animals, Animal Feed, Behavior, Animal, Body Weight, Drinking Behavior, Female, Fungicides, Industrial, Humans, Male, Maternal Behavior, Motor Activity, Oxazoles, Pregnancy, Prenatal Exposure Delayed Effects, Saccharin, Rats, Sprague-Dawley, Rats
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