Received: 30 November 2017 Revised: 16 December 2017 Accepted: 27 December 2017
Reproductive toxic impact of subchronic treatment with
combined butylparaben and triclosan in weanling male rats
Madeha A. Riad
Marwa M. Abd-Rabo
Samy A. Abd El Aziz
Adel M. El
Mohamed M. Badawy
Biochemistry and Chemistry Nutrition Depart-
ment, Faculty of Veterinary Medicine, Cairo
Hormone evaluation department, National
Organization for Drug Control and Research,
Marwa Mokhtar Abd Rabo.
Present address of Samy A. Abd El Aziz and
Adel M. El Behairy: Department of Biochemistry
and chemistry nutrition, Faculty of veterinary
medicine, Cairo University, Giza, Egypt.
Present address of Madeha A. Riad, Marwa M.
Abd-Rabo, and Mohamed M. Badawy: Depart-
ment of Hormone evaluation, National Organiza-
tion for Drug Control and Research (NODCAR),
The effect of treatment with combined butylparaben and triclosan on male gonadal toxicity in
weanling rats was investigated. All treated groups experienced atrophy in the ventral prostate
and seminal vesicle, likewise significant depletion in the number and motility of sperm. Given indi-
vidually or combined butylparaben and triclosan, significantly decreased testosterone, luteiniz-
ing hormone, and follicle-stimulating hormone levels. Individual treatment with tested com-
pounds caused significant elevation in the E
level, whereas combined treatment did not alter
level. Testicular DNA damage was recorded in all treated groups. Moreover, the testic-
ular malondialdehyde level was significantly elevated, along with a significant decrease in cata-
lase enzyme activity in all treated groups. Superoxide dismutase enzyme activity was significantly
decreased in the butylparaben-treated group, increased in the triclosan-treated group, and non-
significantly changed the butylparaben-triclosan-treated group. The combined treatment pro-
duced an endocrine disturbance with a concomitant induction of testicular oxidative stress, which
may represent a common mechanism of endocrine disruptor-mediated dysfunction.
butylparaben, oxidative stress, reproductive toxicity, triclosan
Based on accumulating evidence, exposure to various endocrine dis-
ruptor compounds (EDCs) may disrupt the normal androgen and
estrogen balance in animals and humans, potentially leading to sex
These phenomena have
prompted researchers to address the risks of mixtures of EDCs, where
the adverse effects of EDCs may be derived from mixtures of com-
pounds and not from exposure to a single compound. Several in vitro
studies discussed the effect of combined mixture of EDC using differ-
ent in vitro assay models. The toxic effect of these combinations fluc-
tuated and were synergistic, antagonistic even additive, based on the
nature and concentration of EDCs to enhance toxicity.
Butylparaben (BP) considered a marked preservative in many
personal care and pharmaceutical products.
In vivo studies have
revealed the controversial estrogenic activity of BP in an immature
rodent model. According to research by Oishi,
BP is toxic to
the reproductive system of immature male mice and rats at doses
more than 100 mg/kg bwt. A similar experimental design to that of
was conducted by Hoberman and colleagues
for 3 months
using more animals in each group, and the data revealed that BP did
not alter reproductive organs. By exposing pregnant Wistar female
rats to varying doses of BP indicated that BP act as an estrogenic
agent at a dose of 200 mg/kg bwt, by enhancing aromatase activity
to increase synthesis of estrogen hormone, which lead to depletion
in testosterone levels in offspring male rats.
revealed that BP at doses of 100 or 200 mg/kg bwt did not
change the reproductive organs in offspring female rat.
Triclosan is a potent antimicrobial agent that is widely used as
preservative in personal care products, plastics, and fabrics.
In vivo study revealed the weak estrogenic activity of triclosan
showing that it potentially induced vitellogenin expression in male
medaka while decreasing the hatchability and delaying the hatching in
Moreover, exposure of Japanese medaka fry to different
doses of triclosan or 17 estradiol did not support the hypothesis that
triclosan has estrogenic activity, and thus triclosan is believed to be a
potential weak androgenic agent.
Zorrilla et al.
revealed that oral administration of triclosan with
different doses did not affect the onset preputial separation (PPS),
where testosterone levels was significantly decreased only at a dose
of 200 mg/kg. Conversely, Feng
revealed that administration of tri-
closan, with different doses to pregnant rats, from gestation day 6 to
gestation day 20, decreased offspring uterine weight. Furthermore, it
induced a depletion in human chorionic gonadotropin hormone, E
J Biochem Mol Toxicol. 2018;32:e22037.
2018 Wiley Periodicals, Inc. 1of8wileyonlinelibrary.com/journal/jbt