A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult male offspring rats
The reproductive effects of in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The selected endpoints included reproductive organ weights, testicular function, hormonal status, sexual behaviour and fertility. Two wide ranges of dos...
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| Veröffentlicht in: | Toxicology (Amsterdam) 2006-11, Vol.228 (1), p.85-97 |
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| creator | Andrade, Anderson J.M. Grande, Simone W. Talsness, Chris E. Gericke, Christine Grote, Konstanze Golombiewski, Andrea Sterner-Kock, Anja Chahoud, Ibrahim |
| description | The reproductive effects of
in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The selected endpoints included reproductive organ weights, testicular function, hormonal status, sexual behaviour and fertility. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low-doses were 0.015, 0.045, 0.135, 0.405 and 1.215
mg
DEHP/kg body weight (bw)/day, and the high-doses were 5, 15, 45, 135 and 405
mg
DEHP/kg
bw/day. A reduction in daily sperm production of 19–25% in relation to control was observed in animals exposed to 15, 45, 135 and 405
mg/kg/day. Quantitation of specific cell types shows that the observed effects in daily sperm production are not related to changes in the number of Sertoli cells or their capability to support early stages spermatocytes. A low incidence of cryptorchidism was observed in DEHP exposed groups with a lowest observed adverse effect level of 5
mg/kg/day. Serum testosterone concentration was similar to control at most doses but was significantly increased at 0.045, 0.405 and 405
mg
DEHP/kg/day. In spite of this effect, the weight of seminal vesicle with coagulating glands was significantly reduced at 405
mg/kg/day. Testis, epididymis and prostate weights were similar among groups. Fertility and sexual behaviour were not affected by DEHP treatment at any dose. Overall, our results show that
in utero and lactational DEHP exposure reduces daily sperm production and has the potential to induce reproductive tract abnormalities (of which cryptorchidism seems to be the most sensitive in our rat strain) in male offspring rats. The lowest observed adverse effect levels (LOAELs) for these effects were 15 and 5
mg/kg/day, respectively. Therefore, the no observed adverse effect level (NOAEL) for this study can be set at 1.215
mg/kg/day. |
| doi_str_mv | 10.1016/j.tox.2006.08.020 |
| format | Article |
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in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The selected endpoints included reproductive organ weights, testicular function, hormonal status, sexual behaviour and fertility. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low-doses were 0.015, 0.045, 0.135, 0.405 and 1.215
mg
DEHP/kg body weight (bw)/day, and the high-doses were 5, 15, 45, 135 and 405
mg
DEHP/kg
bw/day. A reduction in daily sperm production of 19–25% in relation to control was observed in animals exposed to 15, 45, 135 and 405
mg/kg/day. Quantitation of specific cell types shows that the observed effects in daily sperm production are not related to changes in the number of Sertoli cells or their capability to support early stages spermatocytes. A low incidence of cryptorchidism was observed in DEHP exposed groups with a lowest observed adverse effect level of 5
mg/kg/day. Serum testosterone concentration was similar to control at most doses but was significantly increased at 0.045, 0.405 and 405
mg
DEHP/kg/day. In spite of this effect, the weight of seminal vesicle with coagulating glands was significantly reduced at 405
mg/kg/day. Testis, epididymis and prostate weights were similar among groups. Fertility and sexual behaviour were not affected by DEHP treatment at any dose. Overall, our results show that
in utero and lactational DEHP exposure reduces daily sperm production and has the potential to induce reproductive tract abnormalities (of which cryptorchidism seems to be the most sensitive in our rat strain) in male offspring rats. The lowest observed adverse effect levels (LOAELs) for these effects were 15 and 5
mg/kg/day, respectively. Therefore, the no observed adverse effect level (NOAEL) for this study can be set at 1.215
mg/kg/day.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/j.tox.2006.08.020</identifier><identifier>PMID: 16996189</identifier><identifier>CODEN: TXICDD</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Administration, Oral ; Animals ; Biological and medical sciences ; Development ; Di-(2-ethylhexyl) phthalate (DEHP) ; Diethylhexyl Phthalate - toxicity ; Dose response ; Dose-Response Relationship, Drug ; Endocrine disruptors ; Female ; Fertility - drug effects ; Genitalia, Male - drug effects ; Genitalia, Male - pathology ; Lactation ; Male ; Male offspring rats ; Maternal Exposure ; Medical sciences ; No-Observed-Adverse-Effect Level ; Organ Size - drug effects ; Plasticizers - toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar ; Reproduction - drug effects ; Reproductive effects ; Sexual Behavior, Animal - drug effects ; Sexual Maturation - drug effects ; Sperm Count ; Spermatozoa - drug effects ; Testis - drug effects ; Testis - growth & development ; Testis - pathology ; Testosterone - blood ; Toxicology</subject><ispartof>Toxicology (Amsterdam), 2006-11, Vol.228 (1), p.85-97</ispartof><rights>2006 Elsevier Ireland Ltd</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-42e1c26afba7b76b9687fc7b76f56b86d96c509e03a4c6554c4e9d07d272c3593</citedby><cites>FETCH-LOGICAL-c509t-42e1c26afba7b76b9687fc7b76f56b86d96c509e03a4c6554c4e9d07d272c3593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tox.2006.08.020$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18218207$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16996189$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andrade, Anderson J.M.</creatorcontrib><creatorcontrib>Grande, Simone W.</creatorcontrib><creatorcontrib>Talsness, Chris E.</creatorcontrib><creatorcontrib>Gericke, Christine</creatorcontrib><creatorcontrib>Grote, Konstanze</creatorcontrib><creatorcontrib>Golombiewski, Andrea</creatorcontrib><creatorcontrib>Sterner-Kock, Anja</creatorcontrib><creatorcontrib>Chahoud, Ibrahim</creatorcontrib><title>A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult male offspring rats</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>The reproductive effects of
in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The selected endpoints included reproductive organ weights, testicular function, hormonal status, sexual behaviour and fertility. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low-doses were 0.015, 0.045, 0.135, 0.405 and 1.215
mg
DEHP/kg body weight (bw)/day, and the high-doses were 5, 15, 45, 135 and 405
mg
DEHP/kg
bw/day. A reduction in daily sperm production of 19–25% in relation to control was observed in animals exposed to 15, 45, 135 and 405
mg/kg/day. Quantitation of specific cell types shows that the observed effects in daily sperm production are not related to changes in the number of Sertoli cells or their capability to support early stages spermatocytes. A low incidence of cryptorchidism was observed in DEHP exposed groups with a lowest observed adverse effect level of 5
mg/kg/day. Serum testosterone concentration was similar to control at most doses but was significantly increased at 0.045, 0.405 and 405
mg
DEHP/kg/day. In spite of this effect, the weight of seminal vesicle with coagulating glands was significantly reduced at 405
mg/kg/day. Testis, epididymis and prostate weights were similar among groups. Fertility and sexual behaviour were not affected by DEHP treatment at any dose. Overall, our results show that
in utero and lactational DEHP exposure reduces daily sperm production and has the potential to induce reproductive tract abnormalities (of which cryptorchidism seems to be the most sensitive in our rat strain) in male offspring rats. The lowest observed adverse effect levels (LOAELs) for these effects were 15 and 5
mg/kg/day, respectively. Therefore, the no observed adverse effect level (NOAEL) for this study can be set at 1.215
mg/kg/day.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Development</subject><subject>Di-(2-ethylhexyl) phthalate (DEHP)</subject><subject>Diethylhexyl Phthalate - toxicity</subject><subject>Dose response</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endocrine disruptors</subject><subject>Female</subject><subject>Fertility - drug effects</subject><subject>Genitalia, Male - drug effects</subject><subject>Genitalia, Male - pathology</subject><subject>Lactation</subject><subject>Male</subject><subject>Male offspring rats</subject><subject>Maternal Exposure</subject><subject>Medical sciences</subject><subject>No-Observed-Adverse-Effect Level</subject><subject>Organ Size - drug effects</subject><subject>Plasticizers - toxicity</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reproduction - drug effects</subject><subject>Reproductive effects</subject><subject>Sexual Behavior, Animal - drug effects</subject><subject>Sexual Maturation - drug effects</subject><subject>Sperm Count</subject><subject>Spermatozoa - drug effects</subject><subject>Testis - drug effects</subject><subject>Testis - growth & development</subject><subject>Testis - pathology</subject><subject>Testosterone - blood</subject><subject>Toxicology</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9uEzEQh1cIRNPCA3BBvoDaw4bx_vHacKraQpEqgRBI3CzHHhNHzjq1vSV5FZ4WR4nUG0iWPIdvxuPfV1WvKMwpUPZuNc9hO28A2Bz4HBp4Us0oH0TdUt4_rWbQAtQdb3-eVKcprQCgaTv2vDqhTAhGuZhVfy6JCQlJxLQJYylSnsyO2OB9-O3GX8SNZMoYA1GjIV7prLILo_IEt5uQpogkB2Jcfd7UmJc7v8Ttzl-QzTIvlVcZyfn1ze3Xi_fkG25iMJPO7gEJWos6JxJGoszkM1krjyRYmzZx_2pUOb2onlnlE7483mfVj483369u67svnz5fXd7VugeR665Bqhum7EINi4EtBOOD1fvS9mzBmRFsDyK0qtOs7zvdoTAwmGZodNuL9qx6e5hb9rufMGW5dkmj92rEMCVJRQlNMPg_2A1cgOAFpAdQx5BSRCvLr9Yq7iQFuTcnV7KYk3tzErgs5krP6-PwabFG89hxVFWAN0dAJa28jWrULj1yvCkHhsJ9OHBYMntwGGXSDkeNxsWSuTTB_WONvw43uEU</recordid><startdate>20061110</startdate><enddate>20061110</enddate><creator>Andrade, Anderson J.M.</creator><creator>Grande, Simone W.</creator><creator>Talsness, Chris E.</creator><creator>Gericke, Christine</creator><creator>Grote, Konstanze</creator><creator>Golombiewski, Andrea</creator><creator>Sterner-Kock, Anja</creator><creator>Chahoud, Ibrahim</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7ST</scope><scope>C1K</scope><scope>SOI</scope><scope>7U7</scope></search><sort><creationdate>20061110</creationdate><title>A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult male offspring rats</title><author>Andrade, Anderson J.M. ; Grande, Simone W. ; Talsness, Chris E. ; Gericke, Christine ; Grote, Konstanze ; Golombiewski, Andrea ; Sterner-Kock, Anja ; Chahoud, Ibrahim</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-42e1c26afba7b76b9687fc7b76f56b86d96c509e03a4c6554c4e9d07d272c3593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Development</topic><topic>Di-(2-ethylhexyl) phthalate (DEHP)</topic><topic>Diethylhexyl Phthalate - toxicity</topic><topic>Dose response</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endocrine disruptors</topic><topic>Female</topic><topic>Fertility - drug effects</topic><topic>Genitalia, Male - drug effects</topic><topic>Genitalia, Male - pathology</topic><topic>Lactation</topic><topic>Male</topic><topic>Male offspring rats</topic><topic>Maternal Exposure</topic><topic>Medical sciences</topic><topic>No-Observed-Adverse-Effect Level</topic><topic>Organ Size - drug effects</topic><topic>Plasticizers - toxicity</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reproduction - drug effects</topic><topic>Reproductive effects</topic><topic>Sexual Behavior, Animal - drug effects</topic><topic>Sexual Maturation - drug effects</topic><topic>Sperm Count</topic><topic>Spermatozoa - drug effects</topic><topic>Testis - drug effects</topic><topic>Testis - growth & development</topic><topic>Testis - pathology</topic><topic>Testosterone - blood</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Andrade, Anderson J.M.</creatorcontrib><creatorcontrib>Grande, Simone W.</creatorcontrib><creatorcontrib>Talsness, Chris E.</creatorcontrib><creatorcontrib>Gericke, Christine</creatorcontrib><creatorcontrib>Grote, Konstanze</creatorcontrib><creatorcontrib>Golombiewski, Andrea</creatorcontrib><creatorcontrib>Sterner-Kock, Anja</creatorcontrib><creatorcontrib>Chahoud, Ibrahim</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Andrade, Anderson J.M.</au><au>Grande, Simone W.</au><au>Talsness, Chris E.</au><au>Gericke, Christine</au><au>Grote, Konstanze</au><au>Golombiewski, Andrea</au><au>Sterner-Kock, Anja</au><au>Chahoud, Ibrahim</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult male offspring rats</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>2006-11-10</date><risdate>2006</risdate><volume>228</volume><issue>1</issue><spage>85</spage><epage>97</epage><pages>85-97</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><coden>TXICDD</coden><abstract>The reproductive effects of
in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The selected endpoints included reproductive organ weights, testicular function, hormonal status, sexual behaviour and fertility. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low-doses were 0.015, 0.045, 0.135, 0.405 and 1.215
mg
DEHP/kg body weight (bw)/day, and the high-doses were 5, 15, 45, 135 and 405
mg
DEHP/kg
bw/day. A reduction in daily sperm production of 19–25% in relation to control was observed in animals exposed to 15, 45, 135 and 405
mg/kg/day. Quantitation of specific cell types shows that the observed effects in daily sperm production are not related to changes in the number of Sertoli cells or their capability to support early stages spermatocytes. A low incidence of cryptorchidism was observed in DEHP exposed groups with a lowest observed adverse effect level of 5
mg/kg/day. Serum testosterone concentration was similar to control at most doses but was significantly increased at 0.045, 0.405 and 405
mg
DEHP/kg/day. In spite of this effect, the weight of seminal vesicle with coagulating glands was significantly reduced at 405
mg/kg/day. Testis, epididymis and prostate weights were similar among groups. Fertility and sexual behaviour were not affected by DEHP treatment at any dose. Overall, our results show that
in utero and lactational DEHP exposure reduces daily sperm production and has the potential to induce reproductive tract abnormalities (of which cryptorchidism seems to be the most sensitive in our rat strain) in male offspring rats. The lowest observed adverse effect levels (LOAELs) for these effects were 15 and 5
mg/kg/day, respectively. Therefore, the no observed adverse effect level (NOAEL) for this study can be set at 1.215
mg/kg/day.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>16996189</pmid><doi>10.1016/j.tox.2006.08.020</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Toxicology (Amsterdam), 2006-11, Vol.228 (1), p.85-97 |
| issn | 0300-483X 1879-3185 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Administration, Oral Animals Biological and medical sciences Development Di-(2-ethylhexyl) phthalate (DEHP) Diethylhexyl Phthalate - toxicity Dose response Dose-Response Relationship, Drug Endocrine disruptors Female Fertility - drug effects Genitalia, Male - drug effects Genitalia, Male - pathology Lactation Male Male offspring rats Maternal Exposure Medical sciences No-Observed-Adverse-Effect Level Organ Size - drug effects Plasticizers - toxicity Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Reproduction - drug effects Reproductive effects Sexual Behavior, Animal - drug effects Sexual Maturation - drug effects Sperm Count Spermatozoa - drug effects Testis - drug effects Testis - growth & development Testis - pathology Testosterone - blood Toxicology |
| title | A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): Reproductive effects on adult male offspring rats |
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