PMID- 19410640
OWN - NLM
STAT- MEDLINE
DCOM- 20090714
LR  - 20131121
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 189
IP  - 1
DP  - 2009 Aug 25
TI  - Effects of in utero through lactational exposure to dicyclohexyl phthalate and 
      p,p'-DDE in Sprague-Dawley rats.
PG  - 14-20
LID - 10.1016/j.toxlet.2009.04.023 [doi]
AB  - Anti-androgenic chemicals alter sexual differentiation by a variety of 
      mechanisms, and the mechanisms between phthalate esters and p,p'-DDE are 
      considered to be different. We performed an in utero through lactational exposure 
      assay using dicyclohexyl phthalate and p,p'-DDE to investigate the sexual 
      differentiation of these chemicals. Pregnant CD (SD) IGS rats were given 
      dicyclohexyl phthalate or p,p'-DDE orally from gestational day (GD) 6 to 
      postnatal day (PND) 20, and the endocrine-mediated effects in dams and their 
      offspring were examined. The reproductive performance of offspring was also 
      examined. The doses of dicyclohexyl phthalate were 0, 20, 100, and 500 mg/kg/day, 
      and those of p,p'-DDE were 5, 15, and 50mg/kg/day. Using the dicyclohexyl 
      phthalate, a dam in the 500 mg/kg group showed dystocia and died. The viability 
      index of offspring on PND 4 decreased in the 500 mg/kg group. Prolonged preputial 
      separation, reduced ano-genital distance, increased areolas/nipple retention, 
      hypospadia, decreased ventral prostate and levator ani/bulbocavernosus muscle 
      weights and decreased testicular germ cells were observed in male offspring in 
      the 500 mg/kg group. In the assay using p,p'-DDE, decreased viability index of 
      offspring on PND 21, prolonged preputial separation in male offspring and early 
      vaginal opening in female offspring were observed in the 50mg/kg group. The 
      copulation and fertility indices decreased in the reproductive performance of 
      offspring in the 50mg/kg group. The endocrine-mediated effects were detected in 
      offspring of dams given 100mg/kg dicyclohexyl phthalate, and in offspring of dams 
      given 20mg/kg p,p'-DDE. Our results suggest that the in utero through lactational 
      exposure assay is a useful method to detect endocrine-mediated effects and that 
      further comparative study between this assay and two-generation reproductive test 
      are necessary when this assay becomes one of the definitive tests.
FAU - Yamasaki, Kanji
AU  - Yamasaki K
AD  - Chemicals Evaluation and Research Institute, 1-4-25, Kouraku, Bunkyo-ku, Tokyo 
      112-0004, Japan. yamasaki-kanji@ceri.jp
FAU - Okuda, Hirokazu
AU  - Okuda H
FAU - Takeuchi, Tetsuya
AU  - Takeuchi T
FAU - Minobe, Yasushi
AU  - Minobe Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090503
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Androgen Antagonists)
RN  - 0 (Phthalic Acids)
RN  - 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene)
RN  - CGD15M7H2N (dicyclohexyl phthalate)
SB  - IM
MH  - Androgen Antagonists/*toxicity
MH  - Animals
MH  - Animals, Newborn
MH  - Animals, Suckling
MH  - Dichlorodiphenyl Dichloroethylene/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Endocrine System/drug effects/embryology/growth & development
MH  - Female
MH  - Male
MH  - Maternal Exposure/*adverse effects
MH  - Phthalic Acids/*toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reproduction/*drug effects
EDAT- 2009/05/05 09:00
MHDA- 2009/07/15 09:00
CRDT- 2009/05/05 09:00
PHST- 2009/03/06 00:00 [received]
PHST- 2009/04/23 00:00 [revised]
PHST- 2009/04/23 00:00 [accepted]
PHST- 2009/05/05 09:00 [entrez]
PHST- 2009/05/05 09:00 [pubmed]
PHST- 2009/07/15 09:00 [medline]
AID - S0378-4274(09)00216-1 [pii]
AID - 10.1016/j.toxlet.2009.04.023 [doi]
PST - ppublish
SO  - Toxicol Lett. 2009 Aug 25;189(1):14-20. doi: 10.1016/j.toxlet.2009.04.023. Epub 
      2009 May 3.