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It was the biggest local news events of 2001, and the hometown paper missed it. Worse, the Sun-Sentinel was scooped by archrival The Miami Heraldon the February 6 murder of Miami Subs founder and cruise-to-nowhere gambling magnate Gus Boulis. Boulis, you've surely read, jumped ship as a young Greek immigrant, built an enormous restaurant empire and an equally gargantuan gambling business, then struck a deal with federal prosecutors that probably led to his shooting on Miami Road just off Federal Highway. While there was nary a mention of Boulis' name in Wednesday's Sentinel, The Herald had details of the killing on all 360,000 front pages.
How did it happen? Herald reporter Wanda DeMarzo hustled. She arrived at the scene quickly after the 9:30 p.m. event, then spent hours talking to people there while ringing others on her cell phone. Her byline appeared on the story along with that of staff writer William Yardley, who was working back at the office. "Wanda is a terrific street reporter," said The Herald's Broward managing editor Rick Hirsch. "Good street reporters don't sit in the office." Indeed the Sentinel didn't show up at all, said Fort Lauderdale police spokesman Mike Reed. (Nor did Sentinel metro editor Rick Robb return a phone call seeking comment.) Sources at the newspaper say there was only one staff writer on duty that night, Shannon O'Boye. O'Boye penned a 3B article about a mysterious shooting, which excluded the identity of the very famous victim. She was already working several other stories, the sources say, so she didn't have time to leave her desk. Police confirmed the dead man was Boulis around 10:30 p.m., quite a while before either newspaper's deadline, but cops are required to inform next of kin before releasing the name to the press. That wasn't done until after midnight, when Boulis' brother-in-law just happened by. "I called Shannon O'Boye about 12:30," Reed says. "She had already gone home."
Who was that Parrothead? Undercurrents has spotted an uncanny facial resemblance between Solee, mascot of the WNBA's Miami Sol, and the fan who wielded a "Free Jimmy" placard at last Tuesday's Miami HeatIndiana Pacers game. The Jimmy in question, of course, is Jimmy Buffett, who was ejected from his courtside seat at AmericanAirlines Arena February 4 after swearing at a referee during a game with the New York Knicks. Compare these pictures of the fan and the mascot, and you have a perfect match, we contend. Given the close corporate ties between the Heat and the Sol, isn't it possible the two teams got together and hatched this supposedly spontaneous act? A Sol switchboard operator acknowledged a similarity in features between the birds but denied that they were one and the same. "It wasn't Solee," she stressed. "He wore green, and Solee doesn't wear green." Yeah, and we have the head of Billy the Marlin sitting right here.
Sacked from his $74K per year job and publicly humiliated by his former bosses at the City of Hollywood, Gary Hakanson has been under attack for a while. Now his kids are caught in the crossfire.
Hakanson, you will recall, was fired as Hollywood's risk manager last March. City bigwigs claimed he cost taxpayers a bundle by mismanaging an insurance fund. Hakanson contends he had angered City Manager Sam Finz, among others, by exposing misuse of the fund. Hakanson is suing to get his job back.
Behind this soap opera is, well, another soap opera. Hakanson divorced his wife in January 2000 and married a Hollywood Police Department secretary, Lisa Laurenzo, this past October. Because the city pays insurance costs for employees' spouses, Hakanson once again has coverage under his ex-employer's program. But Hollywood is not insuring Hakanson's 18-year-old-son or his 14-year-old daughter. Why not? Hakanson's replacement, James Carnicella, who made the call, says he is just trying to save taxpayers a dime.
That's baloney, says former Hollywood city attorney Pamela Terranova, who is representing Hakanson. She says the city has regularly paid insurance costs for stepkids in the past. "They are playing politics," Terranova declares. "Jim Carnicella and Sam Finz are toying with Gary."
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Welcome to Friends of the Canadian Mathematical Society
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Not going to happen until Cowboy Bebop starts showing some interest into the site he pays monthly web hosting for.
Two of the things I love here on AO have been gone for quite some time. I was just wondering if there was any chance we'll see the ability to upload to the gallery or play awesome games on the arcade again.
Not going to happen until Cowboy Bebop starts showing some interest into the site he pays monthly web hosting for.
atomik_sprout (Jan 25, 2011)
Unfortunate... explain to Mr. Bebop that this site is the only suitable place for me to play Asteroids, and that if I don't get to exercise that need, I have brought great shame to my family and its legacy.
atomik_sprout (Jan 25, 2011)
umm... i wasnt here when the arcade was but i wnt it to come back too cuz many forums i am part of havent got an arcade
Hey, i do knight rituals now, just ask me and you can be a knight of Dalmasca
What exactly is wrong with the gallery anyway? I know there were issues before CB went into hiding but what was the issue haha.
More importantly, is there anything at all we can do to fix some of the site problems?
the love you withhold is the pain you carry.
The issue is that the upload script doesn't work.
The gallery software (last I checked), its 3 or 4 versions out of date, and full of security flaws.
And we would go about fixing this how...?
I'd be willing to help if I can, I'm sure that it can't be totally impossible to learn that script stuff.
the love you withhold is the pain you carry.


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Your art is very inspirational to all of us artists and at Shadowness we like to thank our amazing artists for all they do, to show our appreciation for you, your artwork has been featured in todays Daily Inspiration #898
thank you lucifer for your support, feedback and for the choice. i very appreciate it! :)
Aug 26th, 2013 Reply


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HMS Bounty in trouble...
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Re: HMS Bounty in trouble...
Originally Posted by
While some input from the TS community was in poor taste, I do not assign responsibility to them. I'm not even sure they falsely advertised Bounty, as it was inspected, just not to commercial standards for carrying paying passengers.
Wasn't the Coast Guard actually aboard Bounty many times for inspections? There is a link above to dozens of them. They may have been limited in nature, but obviously the hulk passed the rules as they were (and are unlikely to remain). Who was the TSC going to tip off? I'm also not buying that peer pressure would have made a bit of difference either. This was an independently owned vessel, registered as a private yacht. It had to be pretty clear to the professional community that this operation was always trying to skirt the rules and there seemed to be no official violation after years of USCG involvement. It may have been a perfectly safe dockside attraction or fair weather Bay cruiser, how could they know that level of detail. This was simply a dereliction of duty to take this hulk on a passage beyond its capability and the TS community, along with everyone else, was unaware of that decision until it was too late.
I'm not defending the poor taste of the open letter, but none of this disaster should be at the TSC doorstep either. What I find most interesting is that I'm not aware that all the actions of the TS community are even in evidence, or ever will be, and those most insistent on official investigation evidence have been willing to overlook that requirement in this case. Do we know that no member of the TSC ever confronted the skipper or the owner?
Not assigning blame to the TR community for the captain leaving at all.
Just pointing out that they sanctimoniously condemened the ship while they looked the other way at other times. They are the ones themselves who kdsy they new the crew were virtual amateurs. the ship was not maintained well and would not let friends sail; on that ship. And they didnt even tell their "friend" he might me making a mistake when under way.
I am quite sure if they had confronted the skipper or owner they would be trumpeting that all over given their nature for the overly dramatic.
Maybe they do need more regulations.
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Family run home with comfortable en-suite bedrooms, TV, tea coffee making facilities ,refrigerator,hairdryer, recommended New York Times,Cycle California & Lonely Planet Read more
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Nolan's is a long established family run B&B offering its guests a friendly welcome and hospitality for which this area is so famous for. Ann Nolan was nominated for the Irish welcome Award by Failte Ireland! You will feel at home when you arrive! Read more
Sea Crest Farmhouse B&B is a fully working dairy farm, whose elevated location near the village of Quilty boasts splendid views of the Atlantic coastline, proving to be an ideal stop over while touring County Clare. Read more
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Message board »Message Board home »Sign-in or register to get started
Online now: 2 members: Masterblaster48, rh25; 40 anonymousDiscussion: New HOF inductions
Posted | Discussion |
Sept. 10, 2013 StevenL.Imlay Men's 60 77 posts | New HOF inductions I was just informed that Gil Frelly and Dave Birones both Omen 65 players are to be inducted in the Hall of Fame in Las Vegas at SSUSA-Las Vegas National Tournament during the 65 Major Plus tournament this year. I wanted to congratulate both of these players and let you know I will be at the ceremony. Great ball players, teammates and even better people. SLi |
Sept. 10, 2013 DoubleL10 Men's 65 846 posts | I agree with Steve's comments 100%! I have enjoyed playing with both this year! I will certainly be at the induction ceremony. |
Sept. 11, 2013 4x4 Men's 65 599 posts | Echo time...... I also have had the pleasure of playing with Gil and Dave - long time solid ball players & genuinely good people. Congratulations to both..... |


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Delivery: 419-352-7262
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Lmfao – Sorry For Party Rocking
Sorry for party rocking I be up in the party, looking for a hottie to bone I gotta drink in my hand, and they just called Buffalo Popping bottles in the house with models in the V-I-P All the girls make out for the whole damn club to see (Let's go!) People always say that my music's loud, sorry for party rocking! Neighbors complain, sayin' turn it down, sorry for party rocking! Haters don't like me, 'cause I'm the spotlight, sorry for party rocking! When they talk s***, we just be like, sorry for party rocking! Baby baby baby, I'm awfully crazy Off Ciroc, off Patron, s*** whatever's tasty We don't got no manners, hangin' off the rafters Let's go drink for drink, a hundred bucks she on that latest Check my style, take a good look, I'm fresh b**** In my whip with the music so loud I'm deaf b**** Gettin' brains at a red light with people watchin', sorry for party rocking! If you show up already tow up this is what you say, sorry for party rocking And if you blacked out with your sack out This is what you say, sorry for party rocking And if you throw up in a hoes cup This is what you say, sorry for party rocking And if she has a hissy fit cause you whiskey dick This is what you say, sorry for party rocking, oh I don't give a f*** when I'm in the club Sippin' buzz really drunk and I see a fat booty Got to have it I'm a grab it 'cause it's a habit automatic like Uzi, Uzi with the sick flow make a chick go crazy and plastered Tatta it's Redfoo the dude a true party rocka' I'm true to the game too It's called beer pong and I can't loose I got some bad b****es in the back With Ciroc on tap and a bit of little of Gray Goose ooh Oh yeah we kill this s*** With our money we diligent So here is a sorry in advance no hard feelings b****, sorry for party rocking People always say that my musics loud Sorry for party rocking, neighbors complain saying turn it down! Sorry for party rocking, haters don't like we got the spotlight Sorry for party rocking, when they talk s***, we just be like Sorry for party rocking
Lyricsfreak.com © 2015


text: No matter what kind of music you listen to, these headphones deliver full-on stereophonic sound. Powerful enough drive solid, low-end bass and clear enough deliver the highest highs these headphones will please even the staunchest audiophile. They're lightweight, foldable, and good-looking, making them the perfect audio accessory for nearly every device.


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Christmas - love it or loathe it, you can't avoid it. This little book combines seasonal photographs and original cracker jokes for the perfect festive gift.
Martin started his career as a journalist and has worked in senior management, marketing and communications roles for conservation bodies, charities and councils. He has written widely on local heritage and many of his photographs have been published in magazines and books. A number have won competitions. Martin grew up in the Derbyshire Peak District and now lives in the New Forest.
Photoguide to Lymington Published June 15, 2014
Inspiring Images Published June 17, 2012
Office Wit 2 Published October 27, 2011
Alternative Inspirations 2 Published October 27, 2011
Forest Published July 17, 2011
The Book of Playlists Published July 17, 2011
Coast Published July 17, 2011
Photoguide to Lymington Published June 05, 2011


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faculty & staff
Dr. David C. Innes
Chair of the Program in Politics, Philosophy, and Economics; Associate Professor of Politics
Tenure at King's: Aug. 2005 to Present
email@example.com | 212-659-0745
Ph.D. Political Science
Boston College, 1993
M.Div. Reformed Presbyterian Theological Seminary
Pittsburgh, 1997
B.A. Political Science and Philosophy
University of Toronto, 1985
"King's is extraordinary in that the entire faculty is on the same quest to center the life of learning on the wisdom of Christ and to put that in the service of equipping 21st century leaders. It is sweet to be part of that."
Professor Innes came to King's to integrate faith with the study and teaching of politics. He makes that integration in class and in his book, Left, Right, and Christ: Evangelical Faith in Politics (2011). His interest in practical politics is apparent just from peeking into his office. His walls are covered with campaign material from the past half-century. Prof. Innes teaches the Foundations of Politics course in the Core as well as advanced courses in modern and Christian political thought and political economy.
Though a theorist and a Francis Bacon scholar, Prof. Innes writes a weekly column at WORLDmag.com on current political issues. In addition to his work on Bacon, he has also published in The City, The Washington Times, QIdeas.com, Patheos.com, and Relevant magazine. He earned his Ph.D. from Boston College and has taught previously at Assumption College and Stonehill College in Massachusetts, and Geneva College in Pennsylvania. He served as a pastor for several years in Iowa and is still a minister in the Orthodox Presbyterian Church. He lives on Long Island with his wife and four children.


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With such similar family backgrounds, it's no wonder Joe Anderson and Mary Dewane would eventually find each other and marry. Together, they began a journey that led them to establish a winery that would make them, and their fathers, proud -- proud enough that the Benovia name pays homage to Ben and Novian.


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You are here: Home Page > Health and Social Care > Carers > Support for Carers
This comprehensive and easy to navigate carers pack has been designed to provide unpaid carers with a central place to find information regarding all aspects of their caring role. Download the pack here
The Carers Cafe is somewhere the carer, cared for and immediate family can go to meet new people, socialise and enjoy the services being provided. Support and information for carers is available alongside a variety of activities and treatments. These include massages, facials, hairdressing, chiropody and activities such as photography and microwave cooking demonstrations. More information available here
Carers in Bedfordshire have been given funding by NHS Bedfordshire Clinical Commissioning Group to assist carers with costs towards something that would improve their health or wellbeing, allow them to take a break from their caring role or access training.
Carers can apply for a grant of up to £200 towards a service that benefits their health and wellbeing. Visit the Carers in Bedfordshire website for more information.
Carers in Bedfordshire has opened the Carers Lounge based in Bedford Hospital on the ground floor in South Wing. (Follow the signs to the "Committee Room").
At The Carers Lounge you will be able to meet carer support workers and on different days there will be staff that specialise in areas of supporting carers. They are there to offer advice, support and information to visiting carers of all ages and to identify new carers.
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Details of these groups can be found on the Carers in Bedfordshire website
NHS Bedfordshire have provided a grant to support young carers. Young carers under the age of 18 can apply for a grant to go towards a service that will benefit and enhance their wellbeing. More information is available on the Carers in Bedfordshire website
Carers in Bedfordshire run 13 support groups a month for our Young Carers and Sibling Carers that are aged 4 to 16 in order to allow them to be children and to meet other children in a similar situation.
Bedford Borough Council is responsible for social care services within the borough. This section explains how we support people of all ages who may need care either at home or in another setting.


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Vizrt has unveiled the Viz Anchor App for the iPad, an application that runs natively on Apple's iPad and allows users to control newsroom playlists, including video and graphics, directly from the handheld device.
Viz Anchor App integrates seamlessly with existing Vizrt workflows. It provides a subset of Vizrt's control applications and makes that control available on the iPad. With Viz Anchor App, the presenter has an updated version of the playlist available locally and can control video clips and graphics scenes without a PC or queries to the control room.
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This chapter summarizes the scientific literature published since Veterans and Agent Orange: Update 2000 (hereafter, Update 2000; IOM, 2001) on the association between exposure to herbicides and adverse reproductive or developmental effects. The categories of association and the committee's approach to categorizing the health outcomes are discussed in Chapters 1 and 2. The literature discussed in this chapter includes papers that describe environmental, occupational, and Vietnam-veteran studies that evaluate herbicide exposure and the risk of birth defects, declines in sperm quality and fertility, spontaneous abortion, stillbirths, neonatal and infant mortality, low birthweight and preterm birth, childhood cancer, and alterations in sex ratio. Besides studies of herbicides and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), studies of populations exposed to polychlorinated biphenyls (PCBs) are also reviewed when relevant, because TCDD is sometimes a contaminant of PCBs.
The primary emphasis of this chapter is on the potential adverse reproductive effects of herbicide exposure in men, because the vast majority of Vietnam veterans are men. Because about 8,000 women served in Vietnam (H. Kang, US Department of Veterans Affairs, personal communication, December 14, 2000), findings relevant to female reproductive health are also included.
The March of Dimes defines a birth defect as "an abnormality of structure, function or metabolism, whether genetically determined or as the result of an environmental influence during embryonic or fetal life" (Bloom, 1981). Other
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OCR for page 393
Veterans and Agent Orange: Update 2002
Reproductive and Developmental Effects
This chapter summarizes the scientific literature published since Veterans and Agent Orange: Update 2000 (hereafter, Update 2000; IOM, 2001) on the association between exposure to herbicides and adverse reproductive or developmental effects. The categories of association and the committee's approach to categorizing the health outcomes are discussed in Chapters 1 and 2. The literature discussed in this chapter includes papers that describe environmental, occupational, and Vietnam-veteran studies that evaluate herbicide exposure and the risk of birth defects, declines in sperm quality and fertility, spontaneous abortion, stillbirths, neonatal and infant mortality, low birthweight and preterm birth, childhood cancer, and alterations in sex ratio. Besides studies of herbicides and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), studies of populations exposed to polychlorinated biphenyls (PCBs) are also reviewed when relevant, because TCDD is sometimes a contaminant of PCBs.
The primary emphasis of this chapter is on the potential adverse reproductive effects of herbicide exposure in men, because the vast majority of Vietnam veterans are men. Because about 8,000 women served in Vietnam (H. Kang, US Department of Veterans Affairs, personal communication, December 14, 2000), findings relevant to female reproductive health are also included.
The March of Dimes defines a birth defect as "an abnormality of structure, function or metabolism, whether genetically determined or as the result of an environmental influence during embryonic or fetal life" (Bloom, 1981). Other
OCR for page 393
Veterans and Agent Orange: Update 2002
terms often used interchangeably with birth defects are congenital anomalies and congenital malformations. Major birth defects are usually defined as abnormalities that are present at birth and are severe enough to interfere with viability or physical well-being. Major birth defects are seen in about 2– 3% of live births. Birth defects can be detected in an additional 5% of babies with follow-up through the first year of life. The causes of most birth defects are unknown. In addition to genetic factors, a number of exposures—including medications and environmental, occupational, and lifestyle factors—have long been implicated in the etiology of birth defects (Kalter and Warkany, 1983). Historically, most etiologic research focused on the effect of maternal and fetal exposures, but some work has addressed paternal exposures. Paternally mediated exposures could occur via several routes, and therefore exert an effect in various ways. One is through direct genetic damage to the male germ cell that is transmitted to the offspring and expressed as a birth defect. A second is through transfer of chemicals from the work, home, or general environment via seminal fluid with subsequent fetal exposure during gestation. A third route is via indirect exposure from household contamination by take-home exposures.
Summary of VAO, Update 1996, Update 1998, and Update 2000
The committee responsible for VAO found that there was inadequate or insufficient information to determine whether an association exists between exposure to the chemicals of interest (2,4-D, 2,4,5-T or its contaminant TCDD, picloram, or cacodylic acid) and birth defects among offspring. Additional information available to the committee responsible for Update 1996 led it to conclude that there was limited or suggestive evidence of an association between at least one of the chemicals of interest (2,4-D, 2,4,5-T or its contaminant TCDD, picloram, or cacodylic acid) and spina bifida in the children of veterans; there was no change in the conclusions regarding other birth defects. There was no change in those findings in Update 1998 or Update 2000. Reviews of the studies underlying the findings may be found in the earlier reports (see Tables 7-1 and 7-2).
Update of the Scientific Literature
Occupational Studies
No relevant occupational studies have been published since Update 2000 (IOM, 2001).
Environmental Studies
In a pilot study of 30 Vietnamese women who were known or whose spouses were known to be exposed to Agent Orange, Le and Johansson (2001) reported
OCR for page 393
Veterans and Agent Orange: Update 2002
TABLE 7-1 Selected Epidemiologic Studies—Birth Defects
Study Population
Estimated Casesa
Exposed Relative Risk (95% CI)a
Studies Reviewed in Update 1998
Dimich-Ward et al., 1996
Sawmill workers (paternal exposure)
5.7 (1.4–22.6)
Genital organs
1.3 (0.9–1.5)
Garry et al., 1996
Private pesticide appliers (paternal exposure)
1.7 (1.0–2.8)
1.7 (0.8–3.8)
1.7 (1.1–2.6)
Maternal age < 30 years
0.9 (0.5–1.7)
Maternal age > 30 years
2.5 (1.6–2.1)
1.1 (0.5–2.1)
Maternal age < 35 years
1.1 (0.8–1.6)
Maternal age > 35 years
3.0 (1.6–5.3)
All births with anomalies
1.4 (1.2–1.7)
Kristensen et al., 1997
Offspring of Norwegian farmers (maternal and paternal exposure)
1.0 (1.0–1.1)
Studies Reviewed in VAO
Townsend et al., 1982
Follow-up of Dow Chemical plant workers (paternal exposure)
0.9 (0.5–1.4)
Smith et al., 1982
Follow-up of 2,4,5-T sprayers (paternal exposure)—sprayers
compared with nonsprayers
1.2 (0.5–3.0)
Suskind and Hertzberg, 1984
Follow-up of 2,4,5-T production workers (paternal exposure)
1.1 (0.5–2.2)
Moses et al., 1984
Follow-up of 2,4,5-T production workers (paternal exposure)
1.3 (0.5–3.4)
New Studies
Loffredo et al., 2001
Infants exposed to herbicides during the first trimester (maternal exposure)
2.8 (1.3–7.2)
Revich et al., 2001
Residents of Chapaevsk, Russia— congenital malformations
ten Tusscher et al., 2000
Infants born in Zeeburg, Amsterdam, clinics in 1963–1965 with orofacial cleft (maternal exposure)
Births in 1963
Births in 1964
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Study Population
Estimated Cases
Exposed Relative Risk (95% CI)
Studies Reviewed in VAO
Fitzgerald et al., 1989
Follow-up of an electric transformer fire—total birth defects (maternal and paternal exposure)
Hanify et al., 1981
All birth malformationsd
1.7 (1.4–2.2)
All heart malformations
3.9 (1.7–8.9)
Hypospadias, epispadias
5.6 (2.1–15.1)
1.7 (1.1–2.4)
1.4 (0.6–3.3)
Spina bifida
1.1 (0.6–2.3)
Cleft lip
0.6 (0.2–1.5)
Isolated cleft palate
1.4 (0.5–3.8)
Mastroiacovo et al., 1988
Reproductive outcomes of Seveso, Italy, residents (maternal, paternal, and in utero exposure)
Zones A, B total defects
1.2 (0.8–1.8)
Zones A, B, R total defects
1.0 (0.8–1.2)
Zones A, B mild defects
1.4 (0.9–2.6)
Stockbauer et al., 1988
TCDD soil contamination in Missouri (all exposures)
Total birth defects
0.8 (0.4–1.5)
Major defects
0.8 (0.4–1.7)
Midline defects
0.6 (0.2–2.3)
Central nervous system defects
3.0 (0.3–35.9)
Studies Reviewed in Update 2000
Garcia et al., 1998
Infants born with various birth defects in agricultural areas in Spain
Index based on months of work in agriculture and intensity of exposure to chlorophenoxy herbicides
3.1 (0.6–16.9)
New Studies
Kang et al., 2000
Female Vietnam veterans
"Llikely" birth defects
1.7 (1.2–2.2)
"Moderate-to-severe" birth defects
1.5 (1.1–2.0)
Studies Reviewed in Update 2000
Australian Vietnam veterans— Validation Study (paternal exposures)
Down syndrome
92 expected (73–111)
Tracheoesophageal fistula
23 expected (14–32)
16 expected (8–24)
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Study Population
Estimated Cases
Exposed Relative Risk (95% CI)
Cleft lip or palate
64 expected (48–80)
Absent external body part
34 expected (23–45)
Extra body part
74 expected (*)
Michalek et al., 1998
Children with birth defects born to Air Force Ranch Hand veterans (paternal exposures)
Pre-Southeast Asia
0.7 (*)
Post-Southeast Asia
1.5 (*)
Studies Reviewed in Update 1996
Wolfe et al., 1995
High-exposure Ranch Hands relative to comparisons (paternal exposure)
Nervous system
1.6 (0.4–6.0)
Ear, face, and neck
1.7 (0.6–4.7)
Circulatory system, heart
0.9 (0.3–2.7)
Respiratory system
Digestive system
0.8 (0.3–2.0)
Genital system
1.2 (0.5–3.0)
Urinary system
2.1 (0.8–5.4)
0.9 (0.6–1.2)
0.5 (0.2–1.7)
Chromosomal anomalies
All anomalies
1.0 (0.8–1.3)
Studies Reviewed in VAO
Erikson et al., 1984a
Birth defects study (paternal exposure)
Any major birth defects
1.0 (0.8–1.1)
Multiple birth defects with reported exposure
1.1 (0.7–1.7)
EOI-5: spina bifida
2.7 (1.2–6.2)
EOI-5: cleft lip with or without cleft palate
2.2 (1.0–4.9)
Vietnam Experience Study (paternal exposure)
Interview study
Any congenital anomaly
1.3 (1.2–1.4)
Nervous system defects
2.3 (1.2–4.5)
Ear, face, neck defects
1.6 (0.9–2.8)
2.2 (1.2–4.0)
1.2 (1.1–1.5)
5.1 (1.1–23.1)
Spina bifida
1.7 (0.6–5.0)
3.1 (0.9–11.3)
Multiple defects
1.6 (1.1–2.5)
Defects with high exposure
1.7 (1.2–2.4)
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Study Population
Estimated Cases
Exposed Relative Risk (95% CI)
General Birth Defects Study (paternal exposure)
Birth defects
1.0 (0.8–1.3)
Major birth defects
1.2 (0.8–1.9)
Black Vietnam veterans with children with birth defects
3.4 (1.5–7.6)
Digestive system defects
2.0 (0.9–4.6)
Aschengrau and Monson, 1990
Birth defects and father's Vietnam service
Vietnam veterans compared with men without known military service
1.3 (0.9–1.9)
Vietnam veterans compared with non-Vietnam veterans
1.2 (0.8–1.9)
Major malformations
Vietnam veterans compared with men without known military service
1.8 (1.0–3.1)
Vietnam veterans compared with non-Vietnam veterans
1.3 (0.7–2.4)
Donovan et al., 1984
Birth defects and father's Vietnam service (Australia)
Vietnam veterans vs all other men
1.02 (0.8–1.3)
National Service veterans
Vietnam service vs no Vietnam service
1.3 (0.9–2.0)
Follow-up of Air Force Ranch Hand personnel
Birth defects in conceptions after service in Southeast Asia Congenital anomalies
1.3 (1.1–1.6)
Nervous system
1.9 (0.5–7.2)
Respiratory system
2.6 (0.6–10.7)
Circulatory system or heart
1.4 (0.7–2.6)
Urinary system
2.5 (1.3–5.0)
1.8 (0.6–6.1)
2.6 (0.6–10.7)
a Given when available.
b Number of workers with maximal index of exposure (upper three quartiles) for any job held up to three months prior to conception.
c 95% confidence intervals contained one for all outcomes. Anencephaly and spina bifida included in this calculation.
d Excludes stillbirths, neonatal death, or dislocated or dislocatable hip.
* Information not provided by study authors.
ABBREVIATIONS: AFHS, Air Force Health Study; AIHW, Australian Institute of Health and Welfare; CDC, Centers for Disease Control and Prevention; CI, confidence interval; EOI, exposure opportunity index; NS, not significant; SIR, standardized incidence ratio; SS, statistically significant.
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TABLE 7-2 Selected Epidemiologic Studies—Neural Tube Defects
Study Population
Exposed Casesa
Estimated Relative Risk (95% CI)a
Studies Reviewed in Update 1998
Blatter et al., 1997
Offspring of Dutch farmers—spina bifida (paternal exposure)
Pesticide use (moderate or heavy exposure)
1.7 (0.7–4.0)
Herbicide use (moderate or heavy exposure)
1.6 (0.6–4.0)
Kristensen et al., 1997
Offspring of Norwegian farmers—spina bifida (paternal exposure)
Tractor spraying equipment
1.6 (0.9–2.7)
Tractor spraying equipment, orchards or greenhouses
2.8 (1.1–7.1)
Dimich-Ward et al., 1996
Sawmill workers (paternal exposure)
Spina bifida or anencephaly
2.4 (1.1–5.3)
Spina bifida
1.8 (0.8–4.1)
Garry et al., 1996
Private pesticide appliers— central nervous system defects
1.1 (0.5–2.4)
Studies Reviewed in VAO
Stockbauer et al., 1988
TCDD soil contamination in Missouri— central nervous system defects (all exposures)
3.0 (0.3–35.9)
Hanify et al., 1981
Spraying of 2,4,5-T in New Zealand (all exposures)
1.4 (0.6–3.3)
Spina bifida
1.1 (0.6–2.3)
Studies Reviewed in Update 2000
Australian Vietnam veterans—validation study, spina bifida (paternal exposure)
Studies Reviewed in Update 1996
Wolfe et al., 1995
Follow-up of Air Force Ranch Hands (paternal exposure)
Neural tube defects among Ranch Hand personnel childrend
Neural tube defects among comparison children
Studies Reviewed in VAO
Vietnam Experience Study (paternal exposure)
Spina bifida among Vietnam veterans' children
1.7 (0.6–5.0)
Spina bifida among non-Vietnam veterans' children
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Study Population
Exposed Casesa
Estimated Relative Risk (95% CI)a
Anencephaly among Vietnam veterans' children
Anencephaly among non-Vietnam veterans' children
Erickson et al., 1984a,b
Birth Defects Study (paternal exposure)
Vietnam veterans: spina bifida
1.1 (0.6–1.7)
Vietnam veterans: anencephaly
0.9 (0.5–1.7)
EOI-5: spina bifida
2.7 (1.2–6.2)
EOI-5: anencephaly
0.7 (0.2–2.8)
Australia Department of Veterans Affairs, 1983
Australian Vietnam veterans—neural tube defects (paternal exposure)
a Given when available.
b Number of workers with maximal index of exposure (upper three quartiles) for any job held up to 3 months before conception.
c Either or both parents potentially exposed.
d Four neural tube defects among Ranch Hand offspring include two spina bifida (high dioxin), one spina bifida (low dioxin), and one anencephaly (low dioxin). Denominator for Ranch Hand group is 792 and for comparison group 981.
e Number of Vietnam veterans fathering a child with a neural tube defect given any exposure opportunity index.
*Information not provided by study authors.
ABBREVIATIONS: 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; AIWI, Australian Institute of Health and Welfare; CDC, Centers for Disease Control and Prevention; EOI, exposure opportunity index; NR, not reported.
that two-thirds of their children had congenital malformations or developed disabilities within the first few years of life. However, by the authors' own admission, the study subjects were purposely selected to be those who had given birth to at least one disabled child. So, although suggestive for future research, the results may not be amenable to serious interpretation.
Loffredo et al. (2001) reported results from the Baltimore-Washington Infant Study. This case–control study of congenital heart defects in liveborn infants, conducted in 1981–1989, included 1,832 cases of congenital heart defects—66 with transdisposition of the great arteries (TGA) and 114 with non-TGA outflow-tract anomalies—and 771 controls. In 1987–1989, information on exposure was obtained by expanding the original questionnaire to include questions on pesticide exposure for the 1987–1989 period. Information was obtained on type, mode, location, frequency, and time of exposure. A mother was said to be exposed to pesticides if exposure occurred during the 3 months preceding pregnancy or the first trimester, a period of pregnancy considered critical for cardiovascular devel-
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opment. The mothers were further classified into four mutually exclusive groups: mothers not exposed to pesticides at any time 6 months before pregnancy or during pregnancy, mothers exposed to any pesticides 4–6 months before pregnancy, mothers exposed to pesticides during the 3 months preceding pregnancy or during the first trimester, and mothers exposed during the last 4–9 months of pregnancy (late gestational exposures).
The authors report significant associations between TGA and exposures to any pesticide (odds ratio [OR] = 2.0, 1.2–3.3), herbicides (OR = 2.8, 1.3–7.2), or rodenticidal chemicals (OR = 4.7, 1.4–12.1) but not insecticides (OR = 1.5, 0.9– 2.6). Of those, only the models for herbicides and rodenticidal chemicals were adjusted for race of infant, socioeconomic status, maternal age, maternal smoking and alcohol use, family history of heart defects, maternal diabetes, maternal solvent exposures, and paternal pesticide exposures. Non-TGA cardiac outflow-tract anomalies were significantly associated with pesticide exposure (OR = 3.8, 1.4–10.6). All other associations were not statistically significant, and ORs ranged from 0.8 to 1.5. The effect on TGA was stronger among those who used pellet, powder, or food imitators (OR = 4.0, 0.7– 9.8); and effects generally were also stronger with more frequent use of pesticides. For both herbicides and rodenticides, the effects on TGA were pronounced if they occurred during the critical period of pregnancy for cardiovascular development, i.e., the 3 months preceding pregnancy and the first trimester. No data were collected on specific chemicals used, although the authors specifically mention chlorophenoxy herbicides being sold commercially during the period of interest. A major strength of this study is the high response rate, even among controls. Also notable are the specificity for exposures early but not late in pregnancy and the lack of association of herbicides with other heart defects.
ten Tusscher et al. (2000) reported results of a retrospective observational epidemiologic study that compared trends in incidence of nonsyndromal orofacial clefts during 1961–1969 in clinics in the communities of Zeeberg, Amsterdam, and Wilhelmina Gasthuis, Amsterdam. The two locations were different. Zeeberg was highly exposed to potentially toxic chemicals, including dioxins, because of its proximity to open chemical combustion in a nearby incinerator. In fact, the area was still a prohibited terrain as late as 1998 because of the toxic chemical present. Wilhelmina Gasthuis was a clean control location. The authors showed that the trend in incidence of orofacial clefts was consistently higher in the exposed communities than in the control community. There was also a suggestion of a dose–response relationship in that a higher volume of combustion tended to be followed by higher incidence. Note, however, that information on combusted quantities was sketchy. Combusted quantities were generally under-reported (by up to 70%) and unknown for 5 of the 10 years of interest (1960– 1969). In 1961–1969, the incidence in Zeeberg averaged about 2.4 per 1,000 births, with a peak of about 7.1 per 1,000 births in 1963–1965; it later plateaued at 1.7 per 1,000 births (a figure that is still higher than that in the control commu-
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nity in that period). In Wilhelmina, the maximal incidence over the entire 10-year period was 2.3 per 1,000 births. The differences in incidence between the Zeeberg and Wilhelmina Gasthuis clinics were found to be statistically significant for 1963 and 1964.
The results are not based on multivariate models that account for confounding, but the authors outline the comparability of the two populations. Both clinics served communities with low socioeconomic status; hence the need for delivery at the clinics instead of at home. In addition to the social indications that were common to the two clinics, the Wilhelmina clinic handled all pathologic pregnancies. That indicates that the Zeeberg clinic handled healthier pregnancies, despite the observed higher incidence of orofacial clefts. The authors argue, but do not present data, that the two populations are comparable with respect to smoking, socioeconomic status, and alcohol consumption. The study is relevant to the charge of the committee in that chemical emissions from incineration are known to contain TCDD and dioxin-like compounds. Moreover, eels and rabbits from the vicinity of the incinerator were found to have very high concentrations of dioxins in their bodies. The combustion processes, however, were likely to produce multiple chemicals with potential adverse health effects. The nonspecific nature of the exposure information and lack of direct information on potential confounders limit the usefulness of the results of this study for the charge of this committee.
Revich et al. (2001) studied the relationship between the relatively high dioxin concentrations in the air, soil, drinking water, and cows' milk of Chapaevsk, Russia, due to pollution from a chemical plant in the area and its effects on the reproductive health status of the study population. In 369 children born in 1990–1995, the average number of congenital morphogenetic conditions (CMGCs) per child was higher in Chapaevsk, Russia (4.5 in boys and 4.4 in girls), than reported previously in other comparably polluted industrial towns. The most frequent CMGCs were sandals chack, epicanthus, shawl scrotum (in boys), clinodactyly, and broad first fingers. Fequencies of congenital malformations in Chapaevsk were not statistically significantly different from the data reported for the entire continent in the European register.
Vietnam-Veteran Studies
In a historical cohort study of 4,140 female Vietnam veterans and 4,140 female non-Vietnam (but contemporary) veterans, Kang et al. (2000) assessed potential associations between various self-reported pregnancy outcomes and the Vietnam experience or lack thereof. Statistically significant associations were detected only with "likely" (OR = 1.7, 1.2 –2.2) and "moderate-to-severe" (OR = 1.5, 1.1–2.0)] birth defects. Here, "likely" birth defects were defined as congenital anomalies—including structural, metabolic, or hereditary defects—based on an initial 11-category grouping of birth defects. "Moderate-to-severe" birth de-
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fects were defined according to the severity of the diagnosis or were conditions that had any history of surgical or medical treatment or functional impairment or were related to death. The "moderate-to-severe " category was constructed to analyze possibly teratogenic defects. When analysis was restricted to the nonnurse veterans in both groups, the associations between serving in Vietnam and birth defects became stronger for both "likely" (OR = 3.1, 1.8–5.6) and "moderate-to-severe" (OR = 2.6, 1.4–4.9) birth defects. This study has very high relevance to the assessment of effects of Agent Orange and other herbicides used in the Vietnam era, but its usefulness is somewhat limited by the definition of exposure as service in Vietnam. In addition, a serious attempt to validate the self-reported pregnancy outcomes was not generally successful, possibly because of the long gap between the reported events and data collection. However, the rather strong association with birth defects, in the absence of a significant association with any other pregnancy outcome, is rather convincing. Reanalysis of the data in conjunction with forthcoming data from a current study (which is being overseen by the National Academies) characterizing herbicide exposure in Vietnam could yield information valuable for understanding the effects of Agent Orange and other herbicides on birth defects.
The interpretation of the increased risk of CMGCs due to high concentrations of dioxin that was reported in Revich et al. (2001) suffers from poor study design (it used an ecologic study design) and inadequate control for confounding factors. Similarly, the findings of Le and Johansson (2001) suffer from an admitted bias in selection of study subjects.
Of the three relatively well-designed recent studies (Kang et al., 2000; Loffredo et al., 2001; ten Tusscher et al., 2000), Loffredo et al. (2001) and ten Tusscher et al. (2000) do not deal with effects that are directly associated with Vietnam veterans. The positive associations between TGA and use of pesticides and herbicides give some evidence of increased risks that may be relevant to exposure of Vietnam veterans to Agent Orange and other herbicides. However, the stronger results that were associated with exposures during critical periods may not be relevant to Vietnam veterans unless pregnancies occurred during periods of active duty, although the persistence of TCDD implies that direct exposure during pregnancy might not be required.
The results of ten Tusscher et al. (2000) provide evidence of increased risk of nonsyndromal orofacial clefts and a possible dose–response relationship with exposures to potentially high concentrations of dioxins. This study suffers from lack of adjustment for confounders, but its two populations appear to be comparable with respect to potential confounders, such as sociodemographic factors. It is also not possible to rule out confounding by the effects of exposures other than
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polychlorinated dibenzofurans (PCDFs) in 1968 in Yusho, Japan. The study focused on two regions of Japan that were affected by the exposure: Fukuoka and a region of Nagasaki. Using a two-sided binomial test and 85 live births to affected parents in the study area in February 1968 to December 1977, they showed that the sex ratio was not statistically different from the ratio of 0.5 in the general Japanese population. That result is different than the findings in Seveso, Italy, and Yucheng, Taiwan. But, as the authors rightly acknowledged, the exposure in this Japanese study and in the Yucheng study was to PCBs and PCDFs, not to TCDD, as in Seveso (Italy). The study seems to have used appropriate statistical methods for testing the main null hypotheses. It also appears that the study period was too brief to allow for possible effects on sex ratio in offspring of victims who were younger than 19 years old at the time of the incident.
Revich et al. (2001) studied the relationship between the relatively high dioxin concentrations in Chapaevsk, Russia (as detected in the air, the soil, drinking water, and cows' milk because of pollution from a chemical plant in the area), and its effects on the reproductive health of the study population. The sex ratio of births in Chapaevsk was examined with demographic data. The overall sex ratio for 1983 –1997 was 0.5. The year-specific sex ratio ranged from 0.4 for 1989 to 0.6 for 1987 and 1995. The authors conclude that these results support the decline in sex ratio that has been shown in other industrial countries. However, the pattern is not clear. Moreover, the nonspecific nature of the exposure and the poor study design limit the usefulness of these results.
Karmaus et al. (2002) examined the relationship between environmental parental exposure to PCBs and dichlorophenyl dichloroethene (DDE) in Michigan fish-eaters and sex ratio in their offspring. The study was based on a cohort of 1,177 people who were recruited as a result of three surveys (1973–1974, 1979– 1982, and 1989–1991) that assessed total serum PCB concentrations in Michigan anglers. Notably, dioxin-like activity was not assessed in this investigation. A telephone interview was conducted in 2000 to collect data on their children's birth characteristics, such as birth date, sex, birthweight, and gestational age. Exposure data were obtained from analyses of serum PCB and DDE in samples obtained in each of the three surveys. For each birth of a child, the paternal and maternal exposures (dichotomized at the median) that were closest to the birth were used as the most relevant exposures. Logistic-regression models that used the generalized-estimation-equations approach to account for multiple births in a family were fitted to estimate the OR for sex ratio after adjustment for calendar period of the child 's birth, age of the mother at the child's birth, and whether there was an older brother in the family. The models were based on 101 families, which had 208 offspring born after 1963 and paternal measurements of PCB and DDE. The results indicate that a significantly higher OR (with a higher sex ratio) was associated with paternal PCB concentrations over 8.1 µg/L serum (OR = 2.3, 1.1 –4.7). There was no significant association with maternal PCB concentration, but the estimated OR was in the opposite direction (OR = 0.7, 0.4 –1.5). Some of
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the strengths of the study are the attempt to assess the reliability of questionnaire information on a sample of 30 parents (yielding a kappa statistic of 91% and complete agreement on the sex of the children) and the use of appropriate statistical techniques to account for multiple births in a family. But PCB concentrations were determined only at the times of the three surveys, and it was not possible to study the effects of PCB congeners, such as those that display dioxin-like activity.
Vietnam-Veteran Studies
No relevant Vietnam-veteran studies have been published since Update 2000 (IOM, 2001).
Of the four occupational studies evaluated in this section, the two larger studies (Savitz et al., 1997; Schnorr et al. 2001) are of sufficient size to yield results that may be reliable and hence amenable to serious interpretation. Savitz et al. (1997) is a well-designed and well-analyzed case-control study. Schnorr et al. (2001) dealt with a study population with high TCDD exposures, and hence this study is relevant to the charge of the committee. In any case, both studies give evidence of no association of the exposures with sex ratio.
The intriguing finding of excess number of female births in the relatively small study of Okubo et al. (2000) suffers from the shortcomings of the study, one of which is the results may not be specifically attributed to any of the chemicals involved. Moshammer and Neuberger (2000) reported that excess female births were observed after exposures to TCDD in the 1970s, but the results were significantly linked to TCDD load or the interval between exposure and date of birth.
The results from Yoshimura et al. (2001) show lack of association of exposures to sex ratio, contradicting previous results from Seveso, Italy, and Yucheng, Taiwan, but the exposures were to PCBs and PCDFs, not to TCDD. The results from Revich et al. (2001) support previous findings of declining sex ratios in other industrial countries, but this study suffers from poor design. The results from Karmaus et al. (2002) indicate higher sex ORs (more male births) after exposure to PCB and DDE, but exposure data were based on data from three surveys, and it was not possible to study whether the effects were the result of PCB congeners that may have dioxin-like activity.
There is not enough data to determine whether an association exists between exposure to the chemicals of interest and altered sex ratio, but regardless the committee does not necessarily consider this an adverse health outcome. Although a large change in the sex ratio would have adverse effects on the population as a whole, a higher-than-expected number of females may not in itself be an
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adverse event in terms of social or personal capacity on an individual veteran basis. Altered sex ratio might indicate an underlying functional abnormality in one or both parents that might be adverse, such as loss of male fetuses, or alteration of motility of sperm, but altered sex ratio is not necessarily associated with functional deficit in affected persons. Therefore, the committee has reviewed the data but does not treat sex ratio as a health outcome but not an adverse one.
Strength of the Evidence in Epidemiologic Studies
There is inadequate or insufficient evidence to determine whether an association exists between exposure to the chemicals of interest (2,4-D, 2,4,5-T or its contaminant TCDD, picloram, or cacodylic acid) and altered hormone concentrations, semen quality, or infertility; spontaneous abortion; late-fetal, neonatal, or infant death; low birthweight or preterm delivery; birth defects other than spina bifida; and childhood cancers.
Biologic Plausibility
This section summarizes the general biologic plausibility of a connection between exposure to the chemicals of interest (2,4-D, 2,4,5-T or its contaminant TCDD, picloram, or cacodylic acid) and reproductive and developmental effects on the basis of data from animal and cellular studies. Details of the committee's evaluation of data from the recent studies are presented in Chapter 3.
TCDD is reported to cause a number of reproductive and developmental effects in laboratory animals. In males, sperm count and production and seminal vesicle weight have been affected by TCDD. Effects on female reproductive organs have also been seen. The mechanisms of these effects are not known, but one hypothesis is that they are mediated through effects on hormones. Effects on male and female reproductive organs are not always accompanied by effects on reproductive outcomes. On the basis of animal data, there is a biologically plausible mechanism of male and female reproductive effects in humans. In animal studies, offspring of female hamsters given TCDD orally on gestation day 15 had reduced body weight. Although body weight is not consistently reduced in mice and rats exposed to TCDD in utero, those data are suggestive that exposure to TCDD in utero could affect the body weight of newborn humans.
Experiments have examined the effects of TCDD on the adult female reproductive system. TCDD exposure did not increase egg mortality or affect time to hatching of newly fertilized zebrafish eggs, but pericardial edema and craniofacial malformations were observed in zebrafish larvae. In ovo TCDD exposure adversely affected the body and skeletal growth and hatchability of the domestic pigeon but had no effect on the domestic chicken or great blue heron. Immature
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female rats treated with TCDD have been shown to produce significantly fewer ova; the reduction might have a number of pathways, including direct effects on the ovaries and effects on the ovaries that are secondary to effects on other hormone-producing tissues.
Administration of TCDD to male rats, mice, guinea pigs, marmosets, monkeys, and chickens elicits reproductive toxicity by affecting testicular function, decreasing fertility, and decreasing the rate of sperm production. Effects on the prostate have been seen after TCDD exposure. TCDD decreased the concentrations of hormones, such as gonadotropin and testosterone, in rats. High doses of TCDD, however, are required to elicit many of those effects.
TCDD is teratogenic in mice, inducing cleft palate and hydronephrosis. Research indicates that coexposure with either of two other chemicals, hydrocortisone or retinoic acid, synergistically enhances expression of cleft palate. The synergy suggests that the pathways controlled by these agents converge at one or more points in cells of the developing palate. Several reports describe developmental deficits in the cardiovascular system of TCDD-treated animals. Evidence suggests that the endothelial lining of blood vessels is a primary target site of TCDD-induced cardiovascular toxicity; cytochrome P450 1A1 induction in the endothelium might mediate the early lesions that result in TCDD-related vascular derangements. That antioxidant treatment provides substantial protection against TCDD-induced embryotoxicity suggests that reactive oxygen species might be involved in the teratogenic effects of TCDD.
Studies in female rats show that a single dose of TCDD results in malformations of the external genitalia and in functional reproductive alterations in female progeny, such as decreased fertility rate, reduced fecundity, cystic endometrial hyperplasia, and increased incidence of constant estrus. Those effects depend on the timing of exposure.
Little research has been conducted on the offspring of male animals exposed to herbicides. A study of male mice fed various concentrations of simulated Agent Orange mixtures concluded that there were no adverse effects in offspring. A statistically significant excess of fused sternebrae in the offspring of the two most highly exposed groups was attributed to an anomalously low rate of this defect in the controls.
The effects of in utero and lactational exposure on the male reproductive system have been investigated. In utero and lactational exposure to TCDD led to decreased daily sperm production and cauda epididymal sperm number in male rat and hamster offspring. Research suggests that in utero and lactational TCDD exposure selectively impairs rat prostatic growth and development without inhibiting testicular androgen production or consistently decreasing prostatic dihydrotestosterone concentrations. In utero exposure to TCDD also caused decreased seminal vesicle weight and branching and decreased sperm production and increased sperm transit time in male offspring.
Studies in female animals are few but demonstrate that in utero and lacta-
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tional exposure reduced fertility, decreased the ability to carry pregnancy to term, decreased litter size, increased fetal death, impaired ovarian function, and decreased concentrations of hormones, such as estradiol and progesterone. Most of those effects may have occurred as a result of TCDD's general toxicity to the pregnant animal, however, and not as a result of a TCDD-specific mechanism that acted directly on the reproductive system. TCDD also induced changes in serum concentrations of reproductive hormones in immature female rats given TCDD by gastric intubation, partially because of the action of TCDD on the pituitary gland.
The mechanism by which TCDD could exert reproductive and developmental effects is not established. Extrapolating results to humans is not straightforward, because the factors that determine susceptibility to reproductive and developmental effects vary among species. TCDD has a wide array of effects on growth regulation, hormone systems, and other factors associated with the regulation of activities in normal cells; these effects in turn could lead to reproductive or developmental toxicity.
Most studies are consistent with the hypothesis that the effects of TCDD are mediated by the aryl hydrocarbon receptor (AhR), a protein in animal and human cells to which TCDD can bind. The TCDD–AhR complex has been shown to bind DNA and lead to changes in transcription; that is, genes are differentially regulated. Modulation of those genes may alter cell function.
Although structural differences in the AhR have been identified among species, it operates in a similar manner in animals and humans. Therefore, a common mechanism is likely to underlie the toxic effects of TCDD in humans and animals, and data in animals support a biologic basis of TCDD's toxic effects. Because of the many species and strain differences in TCDD responses, however, controversy remains regarding the TCDD exposure that causes reproductive or developmental effects.
Little information is available on reproductive and developmental effects of the herbicides discussed in this report. Studies indicate that 2,4-D does not affect male or female fertility and does not produce fetal abnormalities. However, when pregnant rats or mice are exposed to 4-(2,4-dichlorophenoxy)butyric acid (2,4-DB), of which 2,4-D is a major metabolite, the rate of growth of offspring is reduced, and their mortality increased (Charles et al., 1999); very high doses of 2,4-D and 2,4-DB were required to elicit these effects. 2,4-D has also been shown to alter the concentration and function of reproductive hormones and prostaglandins. One study reported an increased incidence of malformed offspring of male mice exposed to a mixture of 2,4-D and picloram in drinking water. However, paternal toxicity was observed in the high-dose group, and there was no clear dose–response relationship; both findings were a concern in that study. Data have suggested that picloram alone may produce fetal abnormalities in rabbits at doses that are also toxic to the pregnant animals, but that effect has not been seen in many studies. 2,4,5-T was toxic to fetuses when administered to pregnant rats,
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mice, and hamsters. Its ability to interfere with calcium homeostasis in vitro has been documented and linked to its teratogenic effects on the early development of sea urchin eggs. Cacodylic acid is toxic to rat, mouse, and hamster fetuses at high doses that are also toxic to the pregnant mother.
The foregoing suggests that a connection between TCDD exposure and human reproductive and developmental effects is, in general, biologically plausible. However, more-definitive conclusions about the presence or absence of a mechanism for the induction of such toxicity by TCDD in humans is complicated by differences in sensitivity and susceptibility among individual animals, strains, and species; the lack of strong evidence of organ-specific effects among species; and differences in route, dose, duration, and timing of exposure. Experiments with 2,4-D and 2,4,5-T indicate that they can have effects on cells at the subcellular level that could provide a biologically plausible mechanism for reproductive and developmental effects. Evidence in animals, however, indicates that they do not have reproductive effects and that they have developmental effects only at very high doses. There is insufficient information on picloram and cacodylic acid to assess the biologic plausibility of these compounds' reproductive or developmental effects.
Considerable uncertainty remains about how to apply this information to the evaluation of potential health effects of herbicide or TCDD exposure in Vietnam veterans. Scientists disagree over the extent to which information derived from animal and cellular studies predicts human health outcomes and the extent to which the health effects resulting from high-dose exposure can be extrapolated to low-dose exposure. The biologic mechanisms underlying TCDD's toxic effects continues to be an active field of research, and future updates of this report might have more and better information on which to base conclusions, at least for TCDD.
Increased Risk of Disease Among Vietnam Veterans
Given the large uncertainties that remain about the magnitude of potential risk of reproductive and developmental outcomes associated with exposure to herbicides in the studies that have been reviewed, it is not possible for the committee to quantify the degree of risk likely to be experienced by Vietnam veterans because of their exposure to herbicides in Vietnam.
ACS (American Cancer Society). 2001. Childhood Leukemia Resource Center. http://www3.cancer. org/cancerinfo (accessed March 19, 2001).
AFHS (Air Force Health Study). 1992. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Reproductive Outcomes. Brooks AFB: USAF School of Aerospace Medicine. AL-TR-1992-0090. 602 pp.
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AIHW (Australian Institute of Health and Welfare). 1999. Morbidity of Vietnam Veterans: A Study of the Health of Australia 's Vietnam Veteran Community: Volume 3, Validation Study. Canberra: AIHW.
AIHW. 2000. Morbidity of Vietnam veterans. Adrenal gland cancer, leukaemia and non-Hodgkin's lymphoma: Supplementary report no. 2. (AIHW cat. no. PHE 28). Canberra: AIHW.
Abell A, Juul S, Bonde JP. 2000. Time to pregnancy among female greenhouse workers. Scandinavian Journal of Work, Environment, and Health 26(2):131–136.
Arbuckle TE, Lin Z, Mery LS. 2001. An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population. Environmental Health Perspectives 109(8):851–857.
Aschengrau A, Monson RR. 1989. Paternal military service in Vietnam and risk of sponaneous abortion Journal of Occupational Medicine 31:618– 623.
Aschengrau A, Monson RR. 1990. Paternal military service in Vietnam and risk of late adverse pregnancy outcomes. American Journal of Public Health 80:1218–1224.
Alberman E. 1984. Low birthweight. In: Bracken MB, ed. Perinatal Epidemiology. New York: Oxford University Press. Pp. 86–98.
Australia Department of Veterans Affairs. 1983. Case–Control Study of Congenital Anomalies and Vietnam Service. Canberra.
Axmon A, Rylander L, Stromberg U, Hagmar L. 2000. Miscarriages and stillbirths in women with a high intake of fish contaminated with persistent organochlorine compounds. International Archives of Occupational and Environmental Health 73:204–208.
Berkowitz GS, Papiernik E. 1993. Epidemiology of preterm delivery. Epidemiologic Reviews 15: 414–443.
Bertazzi PA, Zocchetti C, Pesatori AC, Guercilena S, Consonni D, Tironi A, Landi MT. 1992. Mortality of a young population after accidental exposure to 2,3,7,8-tetrachlorodibenzodioxin International Journal of Epidemiology 21(1):118–123.
Blatter BM, Hermens R, Bakker M, Roeleveld N, Verbeek AL, Zielhuis GA. 1997. Paternal occupational exposure around conception and spina bifida in offspring. American Journal of Industrial Medicine 32(3):283–291.
Bloom AD, ed. 1981. Guidelines for Studies of Human Populations Exposed to Mutagenic and Reproductive Hazards. White Plains, NY: March of Dimes Foundation.
Bonde JP, Giwercman A. 1995. Occupational hazards to male fecundity. Reproductive Medicine Review 4:59–73.
Bryce R. 1991. The epidemiology of preterm birth. In: Kiely M, ed. Reproductive and Perinatal Epidemiology. Boca Raton, FL: CRC Press. Pp. 437–444.
Buckley JD, Robison LL, Swotinsky R, Garabrant DH, LeBeau M, Manchester P, Nesbit ME, Odom L, Peters JM, Woods WG, Hammond GD. 1989. Occupational exposures of parents of children with acute nonlymphocytic leukemia: a report from the Childrens' Cancer Study Group. Cancer Research 49:4030–4037.
Buckley JD, Meadows AT, Kadin ME, Le Beau MM, Siegel S, Robison LL. 2000. Pesticide exposures in children with non-Hodgkin lymphoma. Cancer 89(11):2315–2321.
Carmelli D, Hofherr L, Tomsic J, Morgan RW. 1981. A Case–Control Study of the Relationship Between Exposure to 2,4-D and Sponatneous Abortions in Humans. SRI International. Prepared for the National Forest Products Association and the U.S. Department of Agriculture, Forest Service.
CDC. 1989. Health Status of Vietnam Veterans. Vietnam Experience Study, Vol. V, Reproductive Outcomes and Child Health. Atlanta: US Department of Health and Human Services.
CDC. 2000. National Center for Health Statistics. National Vital Statistics System. Vital Statistics of the United States, Vol. II, Mortality, Part A, for Data Years 1950–1993. Washington, US Government Printing Office. Data for 1994 to 1998 are available on the NCHS Web site at www.cdc.gov/nchs/datawh/statab/unpubd/mortabs.htm.
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Veterans and Agent Orange: Update 2002
Charles JM, Henwood SM, Leeming NM. 1999. Developmental toxicity studies in rats and rabbits and two-generation reproduction study in rats on 4-(2,4-dichlorophenoxy)butyric acid International Journal of Toxicology 18:177–189.
Daniels JL, Olshan AF, Teschke K, Hertz-Picciotto I, Savitz DA, Blatt J, Bondy ML, Neglia JP, Pollock BH, Cohn SL, Look AT, Seeger RC, Castleberry RP. 2001. Residential pesticide exposure and neuroblastoma. Epidemiology 12:20–27.
Dimich-Ward H, Hertzman C, Teschke K, Hershler R, Marion SA, Ostry A, Kelly S. 1996. Reproductive effects of paternal exposure to chlorophenate wood preservatives in the sawmill industry. Scandinavian Journal of Work, Environment and Health 22(4):267–273.
Donovan JW, MacLennan R, Adena M. 1984. Vietnam service and the risk of cogenital anomalies: a case–control study. Medical Journal of Australia 140:394–397.
Driscoll R. 1998. Epidemiologic Study of Adverse Reproductive Outcomes Among Women in the US Forest Service. Section 2, Health Hazard Evaluation Report No. 93-1035-2686. Washington DC: US Department of Agriculture, US Forest Service.
Erickson J, Mulinare J, Mcclain P, Fitch T, James L, McClearn A, Adams M. 1984a. Vietnam Veterans' Risks for Fathering Babies with Birth Defects. Atlanta: US Department of Health and Human Services, Centers for Disease Control.
Erickson JD, Mulinare J, McClain PW, Fitch TG, James LM, McClearn AB, Adams MJ. 1984b. Vietnam veterans' risks for fathering babies with birth defects. Journal of the American Medical Association 252(7):903–912.
Field B, Kerr C. 1988. Reproductive behaviour and consistent patterns of abnormality in offspring of Vietnam veterans. Journal of Medical Genetics 25:819–826.
Figà-Talamanca I, Traina ME, Urbani E. 2001. Occupational exposures to metals, solvents and pesticides: recent evidence on male reproductive effects and biological markers. Occupational Medicine 51(3):174–188.
Fitzgerald EF, Weinstein AL, Youngblood LG, Standfast SJ, Melius JM. 1989. Health effects three years after potential exposure to the toxic contaminants of an electrical transformer fire. Archives of Environmental Health 44:214–221.
Garcia AM, Benavides FG, Fletcher T, Orts E. 1998. Paternal exposure to pesticides and congenital malformations. Scandinavian Journal of Work, Environment and Health 24(6):473–480.
Garry VF, Schreinemachers D, Harkins ME, Griffith J. 1996. Pesticide appliers, biocides, and birth defects in rural Minnesota Environmental Health Perspectives 104(4):394–399.
Hanify JA, Metcalf P, Nobbs CL, Worsley KJ. 1981. Aerial spraying of 2,4,5-T and human birth malformations: an epidemiological investigation. Science 212:349–351.
Heacock H, Hogg R, Marion SA, Hershler R, Teschke K, Dimich-Ward H, Demers P, Kelly S, Ostry A, Hertzman C. 1998. Fertility among a cohort of male sawmill workers exposed to chlorophenate fungicides. Epidemiology 9(1):56–60.
Heacock H, Hertzman C, Demers PA, Gallagher R, Hogg RS, Teschke K, Hershler R, Bajdik CD, Dimich-Ward H, Marion SA, Ostry A, Kelly S. 2000. Childhood cancer in the offspring of male sawmill workers occupationally exposed to chlorophenate fungicides. Environmental Health Perspectives 108:499–503.
Heidam LZ, Olsen J. 1985. Self-reported data on spontaneous abortions compared with data obtained by computer linkage with the hospital registry. Scandinavian Journal of Social Medicine 13(4):159–163.
Henriksen GL, Michalek JE, Swaby JA, Rahe AJ. 1996. Serum dioxin, testosterone, and gonadotropins in veterans of Operation Ranch Hand. Epidemiology 7(4):352–357.
Hertz-Picciotto I, Samuels SJ. 1988. Incidence of early loss of pregnancy. New England Journal of Medicine 319(22):483–484.
Hertz-Picciotto I, Swan SH, Neutra RR, Samuels SJ. 1989. Spontaneous abortions in relation to consumption of tap water: an application of methods from survival analysis to a pregnancy follow-up study. American Journal of Epidemiology 130(1):79–93.
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Hertz-Picciotto I, Pastore LM, Beaumont JJ. 1996. Timing and patterns of exposures during pregnancy and their implications for study methods. American Journal of Epidemiology 143(6):597– 607.
Infante-Rivard C, Labuda D, Krajinovic M, Sinnett D. 1999. Risk of childhood leukemia associated with exposure to pesticides and with gene polymorphisms. Epidemiology 10:481–487.
IOM (Institute of Medicine). 2001. Veterans and Agent Orange: Update 2000. Washington, DC: National Academy Press.
IOM. 2002. Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans. Washington, DC: National Academy Press.
James WH. 1996. Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels at the time of conception. Journal of Theoretical Biology 180(4):271–286.
James WH. 1997. Reproductive effects of male dioxin exposure. The use of offspring sex ratios to detect reproductive effects of male exposure to dioxins Environmental Health Perspectives 105(2):162–163.
Kallen B. 1988. Epidemiology of Human Reproduction. Boca Raton, FL: CRC Press.
Kalter H, Warkany J. 1983. Congenital malformations. Etiologic factors and their role in prevention (first of two parts). New England Journal of Medicine 308:424–491.
Kang HK, Mahan CM, Lee KY, Magee CA, Mather SH, Matanoski G. 2000. Pregnancy outcomes among US women Vietnam veterans. American Journal of Industrial Medicine 38(4):447–454.
Karmaus W, Huang S, Cameron L. 2002. Parental concentration of dichlorodiphenyl dichloroethene and polychlorinated biphenyls in Michigan fish eaters and sex ratio in offspring. Journal of Occupational and Environmental Medicine 44(8):8–13.
Kerr M, Nasca PC, Mundt KA, Michalek AM, Baptiste MS, Mahoney MC. 2000. Parental occupational exposures and risk of neuroblastoma: A case –control study (United States). Cancer Causes and Control 11:635–643.
Kline J, Stein Z, Susser M. 1989. Conception to Birth: Epidemiology of Prenatal Development. New York: Oxford University Press.
Knobil E, Neill JD, Greenwald GS, Markert CL, Pfaff DW, eds. 1994. The Physiology of Reproduction. New York: Raven Press.
Kristensen P, Irgens LM, Andersen A, Bye AS, Sundheim L. 1997. Birth defects among offspring of Norwegian farmers, 1967–1991. Epidemiology 8(5):537–544.
Larsen SB, Joffe M, Bonde JP. 1998. Time to pregnancy and exposure to pesticides in Danish farmers. Occupational and Environmental Medicine 55(4):278–283.
Le TN, Johansson A. 2001. Impact of chemical warfare with Agent Orange on women's reproductive lives in Vietnam: a pilot study. Reproductive Health Matters 9(18):156–164.
Lindbohm ML, Hemminki K. 1988. Nationwide data base on medically diagnosed spontaneous abortions in Finland. International Journal of Epidemiology 17(3):568–573.
Loffredo CA, Silbergeld EK, Ferencz C, Zhang J. 2001. Association of transposition of the great arteries in infants with maternal exposures to herbicides and rodenticides. American Journal of Epidemiology 153(6):529–536.
Mastroiacovo P, Spagnolo A, Marni E, Meazza L, Betrollini R, Segni G, Brogna-Pignatti C. 1988. Birth deffects in Seveso area after TCDD contamination. Journal of American Medical Association 259:1668–1672 (published erratum appears in JAMA 1988, 260:792).
Meinert R, Schüz J, Kaletsch U, Kaatsch P, Michaelis J. 2000. Leukemia and non-Hodgkin's lymphoma in childhood and exposure to pesticides: results of a register-based case–control study in Germany. American Journal of Epidemiology 151(7):639–646.
Michalek JE, Albanese RA, Wolfe WH. 1998. Project Ranch Hand II: An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides—Reproductive Outcome Update. US Department of Commerce: National Technical Information Service. Report number AFRL-HE-BR-TR-1998-0073.
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Moses M, Lilis R, Crow KD, Thornton J, Fischbein A, Anderson HA, Selikoff IJ. 1984. Health status of workers with past exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the manufacture of 2,4,5-trichlorophenoxyacetic acid: comparison of findings with and without chloracne. American Journal of Industrial Medicine 5:161–182.
Moshammer H, Neuberger M. 2000. Sex ratio in the children of the Austrian chloracne cohort. Lancet 356(9237):1271–1272.
NCI (National Cancer Institute). 2001. Surveillance, Epidemiology, and End Results (SEER) database. http://seer.cancer.gov/ScientificSystems/CanQues (accessed March 19).
Okubo Yasushi(a), Suwazono Yasushi, Kobayashi Etsuko, Nogawa Koji. 2000. Altered sex ratio of offspring in chemical industry workers. Journal of Occupational Health 42(3):147–148.
Pearce MS, Parker L. 2000. Paternal employment in agriculture and childhood kidney cancer. Pediatric Hematology and Oncology 17:223–230.
Pesatori AC, Consonni D, Tironi A, Zocchetti C, Fini A, Bertazzi PA. 1993. Cancer in a young population in a dioxin-contaminated area. International Journal of Epidemiology 22(6):1010– 1013.
Petrelli G, Figa-Talamanca I, Tropeano R, Tangucci M, Cini C, Aquilini S, Gasperini L, Meli P. 2000. Reproductive male-mediated risk: spontaneous abortion among wives of pesticide applicators. European Journal of Epidemiology 16(4):391–393.
Pham TV, Lannigan FJ. 2001. Paediatric laryngeal carcinoma: case report, literature review and possible role of Agent Orange. Australian Journal of Otolaryngology. 4(2):136–139.
Pyeritz RE. 1998. Sex: what we make of it. Journal of the American Medical Association 279(4):269.
Revich B, Aksel E, Ushakova T, Ivanova I, Zuchenko N, Lyuev N, Brodsky B, Sotsov Y. 2001. Dioxin exposure and public health in Chapaevsk, Russia. Chemosphere 43:951–966.
Savitz DA, Arbuckle T, Kaczor D, Curtis KM. 1997. Male pesticide exposure and pregnancy outcome. American Journal of Epidemiology 146:1025–1036.
Schnorr TM, Lawson CC, Whelan EA, Dankovic DA, Deddens JA, Piacitelli LA, Reefhuis J, Sweeney MH, Connally LB, Fingerhut MA. 2001. Spontaneous abortion, sex ratio, and paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Environmental Health Perspectives 109(11):1127–1132.
Schwartz LS. 1998. Health Problems of Women Veterans of the Vietnam War. Doctoral dissertation, Yale University.
Smith AH, Fisher DO, Pearce N, Chapman CJ. 1982. Congenital defects and miscarriages among New Zealand 2,4,5-T sprayers Archives of Environmental Health 37:197–200.
Staessen JA, Nawrot T, Hond ED, Thijs L, Fagard R, Hoppenbrouwers K, Koppen G, Nelen V, Schoeters G, Vanderschueren D, Van Hecke E, Verschaeve L, Vlietinck R, Roels HA. 2001. Renal function, cytogenetic measurements, and sexual development in adolescents in relation to environmental pollutants: a feasibility study of biomarkers. Lancet 357(9269):1660–1669.
Stellman SD, Stellman JM, Sommer JF Jr. 1988. Health and reproductive outcomes among American Legionnaires in relation to combat and herbicide exposure in Vietnam. Environmental Research 47:150–174.
Stockbauer JW, Hoffman RE, Schramm WF, Edmonds LD. 1988. Reproductive outcomes of mothers with potential exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. American Journal of Epidemiology 128:410–419.
Suskind RR, Hertzberg VS. 1984. Human health effects of 2,4,5-T and its toxic contaminants. Journal of the American Medical Association 251:2372–2380.
Tas S, Lauwerys R, Lison D. 1996. Occupational hazards for the male reproductive system. Critical Reviews in Toxicology 26(3):261–307.
ten Tusscher GW, Stam GA, Koppe JG. 2000. Open chemical combustions resulting in a local increased incidence of orofacial clefts. Chemosphere 40(9-11):1263–1270.
Townsend JC, Bodner KM, Van Peenen PFD, Olson RD, Cook RR. 1982. Survey of reproductive events of wives of employees exposed to chlorinated dioxins. American Journal of Epidemiology 115:695–713.
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Tsutsumi O, Uechi H, Sone H, Yonemoto J, Takai Y, Momoeda M, Tohyama C, Hashimoto S, Morita M, Taketani Y. 1998. Presence of dioxins in human follicular fluid: their possible stage-specific action on the development of preimplantation mouse embryos. Biochemical Biophysical Research Communications 250(2):498–501.
Tsutsumi O, Momoeda M, Takai Y, Ono M, Taketani Y. 2000. Breast-fed infants, possibly exposed to dioxins in milk, have unexpectedly lower incidence of endometriosis in adult life. International Journal of Gynecology and Obstetrics 63:151–153.
Tuyet LTN, Johansson A. 2001. Impact of chemical warfare with Agent Orange on women's reproductive lives in Vietnam: a pilot study. Reproductive Health Matters 9(18):156–164.
Watier L, Richardson S, Hémon D. 1997. Accounting for pregnancy dependence in epidemiologic studies of reproductive outcomes. Epidemiology 8(6):629–636.
Wen WQ, Shu XO, Steinbuch M, Severson RK, Reaman GH, Buckley JD, Robison LL. 2000. Paternal military service and risk for childhood leukemia in offspring American Journal of Epidemiology 151(3):231–240.
Wilcox AJ, Horney LF. 1984. Accuracy of spontaneous abortion recall. American Journal of Epidemiology 120(5):727–733.
Wilcox AJ, Weinberg CR, O'Connor JF, Baird DD, Schlatterer JP, Canfield RE, Armstrong EG, Nisula BC. 1988. Incidence of early pregnancy loss. New England Journal of Medicine 319: 189–194.
Wolfe WH, Michalek JE, Miner JC, Rahe AJ, Moore CA, Needham LL, Patterson DG Jr. 1995. Paternal serum dioxin and reproductive outcomes among veterans of Operation Ranch Hand. Epidemiology 6:17–22.
Yen SC, Jaffe RB. 1991. Reproductive Endocrinology. Philadelphia: W.B. Saunders Company.
Yoshimura T, Kaneko S, Hayabuchi H. 2001. Sex ratio in offspring of those affected by dioxin and dioxin-like compounds: the Yusho, Seveso, and Yucheng incidents. Occupational and Environmental Medicine 58(8):540–541.


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Arup understands the life cycle of products, urban development and strategic resources such as water and energy. Through this understanding, we bring an holistic approach to the management of resources and waste.
We help clients rethink their use of finite resources through good design and development of streamlined systems. We find better ways to prevent, reuse, recycle and recover energy from waste.
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Our global network combines local insight with world-leading expertise. We tailor teams of specialists to match clients' needs, whether they require strategic, technical or environmental advice; planning or business case modelling; infrastructure design for waste facilities or project management.
In Sydney, the city authority commissioned Arup to assess waste treatment options and develop a management strategy. Our team addressed highly complex issues in a sector where technology is emerging and often unproven to develop and assess a realistic business case, and a public/private financing and operating model.
Arup's versatility and innovative culture bring fresh thinking to each step in the resource and waste lifecycle. Stakeholders may involve us at different times in a project, but we still join up our experience to tackle the big picture.
In Hong Kong, high population density puts huge demand on local waste disposal. Arup's feasibility study for the North East New Territories landfill extension helped the government respond to concern that landfill capacity would run out before more sustainable infrastructure could be developed.
In 2010 Veolia appointed Arup to lead the design for a sludge treatment facility that will significantly reduce the amount of sewage waste sent to Hong Kong landfills. The facility will generate electricity by incinerating the sludge left after wastewater treatment. The plant will process 2,000 tonnes of sludge per day, two thirds of which will come from Stonecutters Island Sewage Treatment Works – which Arup is also helping to upgrade.
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It may seem odd that we're taking a look at an HD 5850 card in 2011, but Sapphire just released an "Xtreme" edition that's well worth the look. In addition to great pricing, the card features an improved VRM design, a more efficient cooler, and a shorter PCB. But, in the end, it's the $150 price tag that makes this card an absolute winner.
Of all the games we test, it might be this one that needs no introduction. Back in 1998, Blizzard unleashed what was soon to be one of the most successful RTS titles on the planet, and even as of today, the original is still heavily played all around the world – even in actual competitions. StarCraft II of course had a lot of hype to live up to, and it did, thanks to its intense gameplay and superb graphics.
Manual Run-through: The portion of the game we use for testing is part of the Zero Hour mission, which has us holding fort until we're able to evacuate. Our saved game starts us in the middle of the mission, and from the get-go, we build a couple of buildings and concurrently move our main units up and around the map. Total playtime lasts about two minutes.
I dislike StarCraft II more as a benchmark the more I use it, but even with its sporadic minimum frame rates, Sapphire's card still surpassed the other cards in its price-range – and even surpassed the $230 GTX 560 Ti. Given the major boost between the last time we benched the HD 5850 and now, it's clear that AMD has made some major improvements in its driver… the gain is much more stark than in the other games we've tested.


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Georgia police Friday charged two teens with murder a day after a 13-month-old boy was shot dead in his stroller and his mother wounded during a holdup.
Seventeen-year-old De'Marquise Kareem Elkins, the suspected gunman, was charged as an adult with first-degree murder, said Brunswick Police Chief Tobe Green. A 14-year-old companion was also charged with murder but was not identified because he is a juvenile. They were arrested early Friday.
Sherry West said she and her 13-month-old son, Antonio Santiago, were on a walk about 9 a.m. Thursday when they were approached by two young men. The ...


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Wednesday, November 17, 2010
Holiday Mashed Parsnips with Corn, Scallion and Parsley
You've probably already read my Parsnip rant from the other day, so for this post I'll save you the details, and just say "I DID IT!" The best raw vegan Mashed Parsnips EVER! I'm not even joking - there's no part of me that is going to miss Mashed Potatoes this year because I've found my secret weapon to fight the cravings. Of course, it's only replacing starch with more starch, but my sensitive tummy will thank me in the end for not caving to the cooked food that still taunts me.
If you're looking for an alternative to Mashed Potatoes this Holiday season, then I hope you'll give this one a try. Parsnips alone are such an amazing vegetable, and I couldn't be happier to keep them on my menu this year. To me this is Comfort Food in it's finest form, don't be fooled with the Raw Vegan title, there is NO sacrifice here - this dish is so darn satisfying.
Raw Vegan (and WARM)
Holiday Mashed Parsnips with Corn, Fresh Scallion and Parsley
Step 1:
1 & 1/2 c Parsnip - shredded and packed
1 c Cashews (soaked in warm water for 4 -6 hours)
2 tsp Lemon Juice
1/2 tsp Salt (or to taste)
1/2 tsp Nutritional yeast
Lemon Pepper//or//Fresh Cracked Pepper to taste
1/2 tsp Garlic Granules//or//fresh Garlic to taste (this is totally optional)
--- In Food Processor puree the above ingredients until they become a paste. You may need to scrape down the sides of your food processor once or twice.
Step 2.
Add the following to your above puree/paste:
3 Tbsp Walnut Oil//or//Canola Oil
Puree again - for roughly 5 minutes until a thick creamy/whip consistency is obtained.
Step 3.
Add 1/4 c Water and Puree 1 to 2 minutes
Add another 1/4 Water and Puree 1 to 2 minutes
Heating & Serving Your Mashed Parsnips
When you are ready to serve this dish, place the Mashed Parsnips in a mixing bowl and combine the following:
2 c fresh//or//frozen Corn
4 or 5 Scallions (Green Onion) finely chopped
Fold the Corn and Scallion into the Mashed Parsnips.
Into a large Shallow Casserole type dish spread your Parsnip mixture, the larger the dish the thinner you can spread your Parsnip Mixture, and the quicker it will heat in your Dehydrator or Conventional Oven.
Garnish your Parsnip mixture with a Handful of fresh minced Flat Leaf Parsley and Chopped Scallion. I also added a bit more salt and Lemon Pepper.
Proceed with the following Heating Method of choice:
Heating/Warming with a Conventional Oven:
Set your Oven to its very lowest heat, leaving the door closed until your Parsnips Mixture has been Assembled ---
Place your Casserole dish into the warm oven - leaving the door cracked open - for up to 1 hour. Remove when warmed through and ready to eat!
Heating/Warming with a Dehydrator:
Assemble Parsnips as noted above in a Casserole dish. Place dish in your warm in Dehydrator for up to 2 hours. When Mashed Parsnips are warmed through remove from Dehydrator and serve immediately!
Thanks for coming by!
And don't forget to check out these Recipes for your Holiday Menu:
11 comments:
I've recently become OBSESSED with your blog! I've been vegan for many years but never really given raw food a chance. Everything on here looks so delicious and gives me a whole new perspective on raw foods. I need to buy a food processor STAT so I can make this! And every time I look at the Green Bean Casserole dish my mouth waters and I want it in my tummy NOW! Haha. Love your blog! Keep on postin'! :)
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