Autolight and its 96,000 dealers present Miss Joan Bennett in Statement of Mary Blake, a suspense play produced and edited by William Spear. Where did you get those suspenders?  What queer animals on them? Is that a camel? That Hap is a contented camel with a smile from hump to hump. He knows that Autolight's Stay Full Batteries are the batteries that need water only three times a year in normal car use, and that's because they have over three times more liquid reserve than batteries without Stay Full Features. Wow, what's this dancing dervish doing? He's celebrating his release from camel watering. Just got a new Stay Full Battery.  Do Autolight's Stay Full Batteries do handstands too?  And remember too, Autolight's Stay Full Batteries need water only three times a year in normal car use. Anything else, Wilco? Just one more thing. You're always right with Autolight. And now with statement of Mary Blake and the performance of Miss Joan Bennet, Autolight hopes once again to keep you in suspense. I found myself at the far end of a long corridor. The length of it stretching before me in a winding pattern. The walls of it are thick and impregnable cement. There were no windows, only a small opening high on the wall to my right. Through this a single shaft of light fell into a pattern which told me there were iron bars on that one small window. At first it seemed that I was alone in this place. I stood huddled and afraid, unable to move. Somehow I had the feeling that soon I would not be alone. Then faintly, from out of the darkness ahead of me, I heard him coming with slow shuffling footsteps. The walk of a man who has not long been without his eyes. I saw his cane first, a slim thread of white and the blackness before me. I watched it, tapping up and down in a nervous rhythm. Tapping, coming closer, closer I felt the muscles in my throat tighten and an effort to scream. But I made no sound at all, nor did I move. I just stood there and waited and watched him come toward me. Then in the next instant his face was caught in the shaft of light and I saw him very clearly. The searing marks of pain were there and with them the lines born of brooding and evil. And I looked for a long time at that face and I found myself wondering if I could see behind those dark glasses would I find in his sightless eyes any sign of repentance? I remembered suddenly how Gregory Martin had looked the first time I saw him. His tall form standing with casual poise in the doorway. That handsome face creased by the broad smile had been me welcome into his home. Come in, won't you? Thank you. Here, let me take your bag. Thanks. Mrs. Martin isn't here just now, so I'll show you your room. Oh? I think you'll find it very comfortable. In fact, I hope you'll enjoy your life here and your work with me. Oh, I'm sure I will. I'm a little overwhelmed to find myself actually about to work with thee, Dr. Gregory Martin.  Wonderful. Then I'll show you through my laboratory. I felt no fear at all that first day. My room was luxurious and beautiful in the laboratories beyond anything I'd ever imagined in its completeness. I didn't meet Lorna Martin during that first day as a member of the household, but in the evening her husband invited me to join the intimate group of friends that were gathered in front of a glowing fire in their living room. And how about you, Professor? Let me fill your glass. I have my customary toast to make. Yes, my boy. Indeed. I want to join you on that one. Attention, everyone. A toast. The toast to the lovely Lorna, a woman of such abundant charm that it's unfair, really, for one man only to call her his. But three years ago she made her choice and I found that it was such a commendable one that I, for one, think we should forgive her. And so, here's to the lovely Lorna. I joined a Dr. Martin's toast to his wife and at the same time studied the faces of the people who were gathered in a semi-circle around the room. There was a glint on the glass of one man's pincenay that gave his face a weird, somewhat supernatural look. He was smiling broadly in the direction of Mrs. Martin and his teeth and the light of the fire seemed to be made entirely of gold. I looked then at Lorna. She was looking past the others at her husband and although she was smiling I saw that there were tears in her brown eyes. Beneath her polish and exquisite breeding, she was insecure and afraid. Late that night after the party I was thirsty so I put on my robe and went quietly down the carpeted stairs. The big double door that led into the living room was closed but I could see that a lamp was lit inside the room and then as I passed by I heard her. She was sobbing softly. I turned quickly to go back to my room. I didn't want to be placed in the embarrassing position of hearing something I shouldn't. But before I'd gotten out of earshot I heard her sobbing stop suddenly with a noise that sounded like the flat of her palm hand hitting hard against a cheek. Next morning I was working with Dr. Martin and loving every minute of it. We worked silently swiftly with no regard for anything outside of the task immediately at hand. That is, save for one little thing. Dr. Martin seemed fascinated with a little vial of amber liquid which he kept on a desk. Price he abandoned his work to walk over to her. Lift the glass container up to the window and study its contents. His lips forming a strange half-smile. Well yes, that's it of course. What? I beg your pardon Dr. Martin, were you speaking to me? No, no Miss Blake. Talking to myself I expect. Scientists frequently do I understand. Yes, I've heard so. My foreman Miss Blake, I just realized it's almost the color of her hair isn't it? The lawn as I mean. My wife is very pretty here don't you think? I think Mrs. Martin is a beautiful woman in many ways. That's a rather generous opinion to form as so short of time isn't it? Do you always analyze people so quickly and so flatteringly? How about me for instance? I don't think you're being fair Doctor, but since you asked I'd say you're a man of great charm and certainly a scientist of remarkable ability. I should be pleased I suppose. However it sounds like generalities. I think I'll have to see what I can do toward creating a more specific impression. Yes, truly beautiful color isn't it? I've never seen anything quite that shade of amber, what is it Doctor? It's a mixture of my own. I'll let you in on it some day, soon. But meanwhile I'd advise you to keep clear of it. I think I could safely claim it to be the fastest acting poison in existence. A new experiment Doctor? The most exciting experiment to which a scientific mind can apply itself. And I have every confidence that I'll be able to work it out to a successful conclusion. Sounds challenging, Dr. I hope I'll be allowed to work on it too. I assure you my dear Miss Blake, I wouldn't attempt this particular experiment without you. Neither of us made mention of his poison again and indeed it seemed that the Doctor had quite forgotten. We were both working hard on the completion of his current project. Lorna Martin worked with us part of the time and was only then that I learned she had previously always assisted her husband with his work. It was in fact Lorna who suggested the final step that led him quickly to the result he had been striving for. We worked from early morning until late at night. And on the third day towards midnight the project was completed. We had a late supper and after a glass of liqueur I left the Doctor and his wife and went to my room. Yes? Were you asleep? Oh no, no I was just sitting here relaxing Doctor. I'm still too excited to do any sleeping. Well that's exactly how Lorna and I found ourselves feeling. So we decided to sit up and talk a bit over another glass of liqueur. We wanted if you'd join us. After all, this has been a three way victory Miss Blake. We want you in on our triumphal toast. Oh that's a generous thought. I'm afraid I wasn't much more than a spectator in this instance. Oh nonsense, come along. Well I am certainly eager to talk with Mrs. Martin. I had no idea she was an active colleague of yours in the laboratory. Oh yes, Lorna's been a tremendous help to me. In the past I would say she's been quite indispensable. Lorna's brilliant mind amazed me from the first moment I met her. Here we are. Lorna my dear, Miss Blake and I were just having a most engrossing conversation. Holy about you. It seems Miss Blake has been greatly impressed by the work you've done on this idea of mine. Oh Doctor Martin, you're making it sound as if I had minimized your own work. I didn't mean it. Of course you didn't. I do understand. And you needn't make apologies in my direction for your appreciation of my wife's talents. Here now. It'll occur for you Miss Blake. Same as earlier. Please. There you are. Thank you. Lorna dear, how about you?  Let me see. A person that you haven't even touched. In the few seconds that have passed since Doctor Martin and I had entered the room, three distinctly sharp and clear thoughts had crossed my mind in sudden quick succession. And each of them struck at my insides like the painful puncture of a thin sharp blade. One that Doctor Martin professionally was insanely jealous of his wife. Two that it was totally unlike Lorna Martin not to speak to us as we entered the room. And three that Doctor Martin had just gone over to his wife to make absolutely certain that she was dead. The light is bringing you Miss Joan Bennett in statement of Mary Blake. Tonight's production in radio's outstanding theatre of thrills. Suspends. Can I get a pair of those auto light stapled battery suspenders? Uh, Hap, there's a catch to these suspenders. Of course. Wouldn't these suspenders without a catch? Well, to get a pair of these, you'll have to rave about that special feature of the auto light stapled battery, the fiberglass retaining mat that protects every positive plate to keep the power producing material in place for longer life. Seventy percent longer life, in fact, than batteries without stapled features. And this is proven in recent tests based on SAE life cycle standards. Doesn't anyone but you have a pair of those wonderful, wonderful suspenders? No, no, these suspenders were made for me by a happy car owner who recently bought an auto light stapled battery, the battery that needs water only three times a year in normal car use. Said he couldn't thank me enough for telling him about it. So friends, see your auto light battery dealer tomorrow. And remember, you're always right with auto light. And now auto light brings back to our Hollywood soundstage our star Miss Joan Bennett in statement of Mary Blake. A tale well calculated to keep you in suspense. I stood there unable to speak. Dr. Martin looked at me. He was amused, amused at my reaction to his wife's murder. I rather think I could read your mind quite accurately at this moment, Miss Blake. Why, why, why does one do anything? What motivates any action of man? There is a need, a desire, a one behind every action.  It's as simple as that. A poison. Yes. Come into the laboratory. A poison. We'll look for it. It isn't on your desk. You did kill her with it, but I don't see it. And why have you made it a point to have a witness? I remember now. You talked of this as an experiment and you told me I would work with you on it. Just what, what do you... Patience, my dear girl, patience. What is the next step, doctor? To call whom? The police and tell them what? When one discovers that one's wife has been murdered, one naturally calls in the authorities. Oh, yes, surgeon. Now listen carefully, please. This is Dr. Gregory Martin. My address is 12448 Pilgrim Drive. Would you send some men over immediately, please? My wife has just been murdered. The complete realization of what he had done seemed to come upon me all of once. A sudden delayed shock that hit me with the impact of a hammer blow. I looked at him and he seemed a total stranger. A maniac whose next move I could not predict. He was laughing, and while he laughed, I reached desperately behind me, posing my fingers tightly around the glass container I felt then. And I prayed that it contained something that would serve as an effective weapon against the murder. With one quick movement, I swung it full on his laughing face. I washed it, ate away his skin like a sheet of tissue paper in a soaring flame. When the police arrived, they found Lorna Martin seated erect and beautiful in the chair in the sitting room, while her husband writhed in pain on the floor of his laboratory. I was at Dr. Martin's desk, they said. I remember lifting my eyes to follow mutely the movements of the men who screamed into the room. Through the door, I could see them bending over the body of Lorna Martin. And I watched with a strange detached curiosity as two interns administered temporary treatment to Dr. Martin's injuries. Then they took us away. The three of us. I don't remember much about it. Do you want to talk now? Come now, Miss Blake, we realize that you've been under a great strain. We want to find out exactly what happened and we must know exactly what part you played. You know, in view of what has happened to Dr. Martin and his wife, a man so revered and well-known, we will be subjected to a great deal of pressure to bring someone to justice for this thing. Justice? How can Lorna Martin ever know justice? Let's hear your story, Miss Blake, from the beginning. There were three people alone in that house when this happened. And of them, only you were able to speak. Now, let's hear what you have to say. How about it? You'll talk on the stand. You was like a green steam. The setting now is a court of justice. And I sat numbly among strange faces and gesturing hands and questioning voices. I could hear words tumbling forth, men. How long and how well you have known Dr. Gregory Martin, please? Dr. Martin has been my close friend and associate for over a dozen years. His fine character cannot be questioned. He and his wife were an unusually devoted couple of this thing that has happened. Do you relate to the court any scenes you witnessed in the Martin household, which might have an important bearing on this case? I attended a gathering at the Martin home on the very night that Miss Blake first came there. She sat with us in the living room and throughout the evening I was aware of her studying, Dr. Martin, with a peculiar intensity. It was extremely... In this case, will you please tell the court your findings, which revealed the cause of Lorna Martin's death? Mrs. Martin was poisoned. The poison was in liquid form taken internally. It was obviously expertly prepared by someone well acquainted with scientific formulas. Someone who had access to an excellently equipped glass from which Lorna Martin drank the poison that killed her. We found on the glass the prints of Mrs. Martin and those of Mary Blake. And no others? No, sir. No others. Did you discover any more of the poison like that which was used to kill Mrs. Martin? There were several drops of it left in the glass from which Mrs. Martin drank. Later, during our investigational search of the entire house, more of the poison was found. And will you please tell the court where the remainder of that poison was found? Yes, sir. In a perfume bottle on the dressing table in the room of Mary Blake. The voices floated in and out and around the room. In some of the words hit against the walls and echoed back at me. Then I rode on them to the front of the room and the voices were loud and strange and my senses seemed blocked by them and by a hand that pointed towards me and a face that swung down at me like an inflated comic balloon. I almost laughed. Perhaps I did. Can you, Mary Blake, in any way account for the fact that only Mrs. Martin's and your own fingerprints were found on the glass of poison? Can you give the court any explanation for the perfume bottle containing the remainder of the poison being found in your room? Mary Blake, can you in any way explain the testimony we have heard repeatedly during this trial of your unusually strong personal interest in Dr. Martin? The words were strung like beads on a string and wound round and round me until I felt them so tight it seemed I couldn't breathe. Then suddenly the voices strangling me with the words came through to me clearer and louder than ever before. And this time the words were built in a big stick and it was carefully aimed and swung straight towards me. The prosecution at this time is able to bring forth its most important witnesses. We ask, however, that you consideration be given him by all those present in this courtroom, as his condition is still very serious. He has suffered from extreme shock. And as a result of the injuries he recently sustained, he is and will forever remain totally blind. Now, clerk, will you please inform the nurse outside that you may now bring the doctor into the courtroom? The prosecution calls to the stand, Dr. Gregory Martin. He came in, seated in a wheelchair.  There was something about seeing so handsome and powerful a figure so completely incapacitated. An involuntary gas to escape from my own lips as well as from those of every person in the crowded courtroom. Without a word being spoken, the prosecution had easily scored its most effective point. And after Dr. Martin had finished his spoken testimony, the big stick of words came down upon me with full force. We find the defendant guilty as charged. Then more words, words coming at me with final flattening blow. This court hereby sentences you to the women's state penitentiary for a period of not less than 99 years. I found myself at the far end of a long corridor. The length of it stretching before me in a winding pattern. The walls of it are thick and pregnable cement. There were no windows save for a small opening high on the wall to my right. Through this, a single shaft of light fell into a pattern which told me that there were iron bars on that one small window. At first it seemed that I was alone in this place. I stood huddled and afraid, unable to move. Somehow I had the feeling that soon I would not be alone. Then faintly, from out of the darkness ahead of me, I heard him coming with slow, shuffling footsteps. The walk of a man who has not long been without his eyes. I saw his cane first. A slim thread of white in the blackness before me. I watched it, tapping up and down in a nervous rhythm. Tapping, coming closer, closer. I felt the muscles in my throat tighten in an effort to scream. But I made no sound at all, nor did I move. I just stood there and waited and watched him come toward me. Then in the next instant, his face caught in the shaft of light and I saw him very clearly. Mary, Mary, please wake up. Come on now, get hold before you rob the whole block. Come on now. We can't have this every night. Oh, how's that dream? I can't stop dreaming. It isn't fair, it isn't fair. I don't belong here. I didn't do anything. But I'm here.  There you see, Warden, that's the way it is every night. We can't seem to do anything. That's enough, ma'am. We're releasing Mary Blake. You're free, Miss Blake. The nightmare is over. Come with me and I'll tell you what has happened. These weeks of freedom it wrongly took from you. Now, of erasing the shock and heartbreak you've been forced to suffer, we can only hope that it is not too deeply embittered you and hasn't totally destroyed your faith in the justice one customarily finds in our courtrooms. There seems to be a limit to bitterness, Warden. I find that what I feel now is not a release from injustice, but a release from fear. I know that he can never reach me again. Even in my dreams, how can I be so sure of that? Well, it's another of the things that can't be accounted for rationally about this case. It leads one to wonder if some... Oh, some metaphysical force wasn't put to work in place of the erring machinery of justice.  And over the period of time that has lapsed since the day you received sentence, it seems the doctor's mind would not free him from one particular visual experience. He too suffered from a recurring dream, which due to his impairment was inflicted upon his waking as well as sleeping hours. The dream? Did he describe it? Oh, he did. In detail. It seemed that there was... I entered a narrow corridor. With my hands, I... felt that the walls were of a thick impregnable cement. The tap of my cane produced an echo that told me the corridor was one of interminable winding links. I did not want to enter nor walk through it, yet it seemed that I was forced to. I was walking, walking. It seemed endless. I wanted to cry out, but could find no voice. I wanted to see a single light from a window or an open door to know that there was somewhere an end to the blackness. But there was no light and no end. I wanted to turn back, but there was no turning back and no end to my walking. And although I had the feeling of being alone in this place, I knew that I was not alone and never would be and it was worse than being alone. Although I could not see her, although she did not touch nor speak to me, I knew she was there and for me, she would always be there. Mary Blake, my accuser, for she is the innocent and I am the guilty and for the innocent there is always a freedom and for the guilty there is never an escape. Well, Hap, you sway me, but let me sway, I mean say, a word about the more than 400 products made by Auto Light for cars, trucks, planes and boats in 28 plants coast to coast. These include complete electrical systems used as original equipment on many makes of America's finest cars, spark plugs, batteries, generators, coils, distributors, electric windshield wipers, starting motors, bullseye sealed beam headlights, all engineered to fit together perfectly, they're a perfect team. So friends, don't accept electrical parts supposed to be as good, ask for and insist on Auto Light original factory parts at your neighborhood service station, car dealer, garage or repair shop. Remember, from bumper to tail light, you're always right with Auto Light. Next Thursday for suspense, our star will be Mr. John Lund. The play is called The Man in the Room and it is, as we say, a tale well calculated to keep you in suspense. Tonight's suspense play was produced and edited by William Spear and directed by Norman McDonnell. Music for suspense is composed by Lucian Moraweck and conducted by Led Bluskin. Statement of Mary Blake is an original play written for radio by Shirley Gordon. Ms. Joan Bennett will soon be seen in the MGM production, Father of the Bride. In the coming weeks, you will hear such stars as Claire Trevor and Charles Boyer. Don't forget, next Thursday, same time, Auto Light will present suspense John Lund. Resister or regular spark plugs, Auto Light electrical parts at your neighborhood Auto Light dealer. Switch to Auto Light. Good night. This is CBS, the Columbia Broadcasting System.


es it's a really critical point I think and so and they're not subject to ascertainment bias the exposure assessment was totally divorced from the outcome data so CDC didn't know our data and we didn't know the exposure measures so this is a great strength of these studies as a group let's here's a little calculation that you can do I did it roughly and not very you know not very carefully but you can do this more carefully so almost all these findings are in males let's say there are 30 studies here I too I think had findings in females the chance that this would happen by a toss of a coin is infinitesimal so this is the fact that these findings are in males almost exclusively is not the result of chance and the fact that DHP and DHP metabolites repeatedly turn up as most strongly associated and apologies to Earl you said there were equipotent I don't know maybe in rats but in human studies I would say overwhelmingly it is DHP as far as we've looked now we have there many we have not been able to look at for example the phthalates for which we only have the monoester metabolite which is not going to characterize human exposure very well I can't speak to those but when and we learned this from DHP when we looked similarly at MEHP we didn't get a very good picture when we as we add in the subsequent metabolites the secondary tertiary metabolites were starting to get much more better handle on exposure so the fact that these turn up as primate you know the primary candidates that are showing a positive is not a chance currents again if we if we just assigned positive associations at random with all the 15 metabolites and Tony caliphate measures or the nine phthalates you would not see this picture this is not a random picture so I would say that yes the individual studies are imperfect this is in humans we're very young science although the animal data has gone back to the 80s the human data aside from one study in 200 2001 and 2003 basically has been last five years so we have a new science it's imperfect but I think as a body of evidence it suggests that there is risk to multiple systems and we have to follow this further thank you questions press I guess I'll start thank you that was a nice summary of all the literature just I guess I don't really have specific questions about the study but more of overall impression of the literature and you kind of close with statement that this is new science and it's imperfect but in thinking about epidemiologic studies and we had a bit of discussion on this yesterday when we heard another presentation about environmental epidemiology in the use of the term you know imperfect I mean would you say that these studies are more imperfect than other areas of environmental epidemiology or are you finding that they're having similar limitations and that's a really good question and I think that when the exposures are high and limited you know to point sources so they so possibly or you know limited number of environmental studies where you have very clear point exposures I think you can do better I think that for I think that for something like lead which we have studied now for what almost 30 years we have a lot more information we really understand lead exposure a lot better both how to measure it you know what it does and so on so I think that might be a sort of comparable you know more you might hope to get with these but for the vast majority of exposures the PCB you know human effects of PCBs and certainly bisphenol A we know a lot less and dioxins and so on I think we're probably on a par with those but it would be fair to say that the limitations that this literature is facing are similar to you know studies that are done on air pollution or metals and then some of the main limitations are some that you touched on include you know sample sizes you know specifically your some of the earlier AGD studies were small the use of a single urine sample to assess exposure in terms of the effects of these limitations on our ability to detect associations I mean would you think that they may make it more likely that we would detect associations less likely I mean because these are limitations that are you know frequently pointed out and you know this literature as well as other environmental literature sample size timing of exposure critical windows so timing of exposure is important because of the variability of exposure on the other hand your study and Jane Hoppin study and so on suggest that while there is variation across time periods correct me if I'm wrong but my understanding is that if you are low you tend to have low exposure to a particular phthalate or group of phthalates like you're in the lowest quartile then you will tend to be in that lowest quartile and similarly if you're high you will tend to stay high so it's not perfect by any means and in our new study we're going to get a sample in each trimester which is better but as I pointed out what this introduces is exposure misclassification so you're not getting it at quite the right time so you're putting an error in your exposure measure that exposure misclassification unless it was how different in say boys with shorter long AGD which is hard to imagine is going to lead to an underestimate of the effect so that would make it harder to detect an effect and of course having a small sample makes it harder to detect an effect certainly we couldn't look at hypospadias for example at all but we can't conclude from our studies that this is not associated with hypospadias for that we would have to have a study of the size of the National Children's Study I think so I think that while there are limitations and I'd be the first person to admit that I think the fact that we have so many positive associations should we should take that seriously a different set of questions more in terms of the outcome and defining what's an adverse outcome or not some of the studies you presented have small changes in outcome like a gestational day change of one or two days and maybe a small change in AGD can you comment on how to interpret these small changes in terms of whether they're adverse or not and touching on kind of adverse population differences which again is something we've discussed a bit yesterday so let me take them separately well there's two points one is that we will be publishing a study which I'll share with the committee showing that AGD is a correlate of a clinical outcome that I think everyone would consider adverse and there is a published study although it's small linking well relating showing that hypospadias and cryptorchid particularly hypospadias spadiac children have a shorter analgenital distance so we're beginning to get some clinical correlates so AGD itself is probably not adverse but if it is a marker or a fetal disruption then it is a marker of an adverse event and I think it's important to make that distinction as far as the population versus the individual level I like to just refer and I don't know if you've talked about this yesterday so stop me if you have but I like to think about the model of lead and IQ did you talk about that you did okay but you're free to mention it again if you want well just that a 10 percentage point change in IQ that might be induced by prenatal lead exposure or postnatal will not have probably affected an individual so probably if your kid has an IQ of 105 versus 95 or whatever probably doesn't matter that much that kid as a whole it makes a huge difference in the percent of children who are going to need remedial care and special education so I think it's the same situation we see that with our sperm count too we get a shift in the mean of the sperm count between two populations not very different but the percent of men who are subfertil changes hugely so the effect of a population shift is in the tail and that's the reverse effect it's the increase in that tail that's adverse to the population and then one other quick question and then I'll let other people do you I'm sure you have stored urine samples but have any of the DINP metabolites been measured or is that in the plans so I talked to Antoni about this Antoni Caliphate and she said that it's not useful is that yet until she is measuring the secondary metabolites because we don't get a good measure of human exposure I have a question relating to one of our key issues and that is which phthalates to focus on we had before the break from the good Dr. Foster when he was six years old conducting these structural activity relationships and it transpires if I understand this correctly also phthalates with a side chain length of between four and six carbons are the ones that are of concern in the rat and probably also by extrapolation in the human Dr. Grays there's no you are finding positive responses with seven okay but what you did not see and I saw this from your table and also from some of your data you presented Paul that with the more volatile lower molecular weight or phthalates there is next to nothing to be observed in the rat model Shana you have presented a lot of of epidemiological studies to us today where we have indications for example the almond that are from 2008 with the hairspray we have hairspray has a lot of low molecular weight phthalates and there were associations with hyperspaters and and there were other examples in some of your the studies which you've cited which would suggest I'm trying to be very careful indirect evidence that the lower molecular weight phthalates or the more volatile ones may also be associated with some of the end points of concern how can we reconcile this could you comment on that it's I think pretty important for us because we have to decide which phthalates we have to take into account so I think a big one to talk about is DEP so DEP is interesting because I think most of our exposure as humans is through cosmetics personal care products and very high I mean you get a lot of it and it has been associated in our study with antigenal distance as you say in the Orman study so what's going on here why do we see this discrepancy and that's something we've talked about a lot I see a couple of explanations one is that we what we're seeing is chance which is always a possibility one is that it's implausible that the rat model would be good for some phthalates and not others but not impossible you know good human model the third is that the route of exposure matters and I don't know how to address that and I I feel as an epidemiologist statistician you know sort of infinite as to how to what to do about that but we get cosmetics and personal care product exposure through our dermal and through inhalation and all of the dosing that I know of in these studies to rodents has been through gavage and diet so what not much so that's I would be extremely interested and I know it's difficult to do a dermal study in rodents but I think it would be really interesting to see because the metabolism of the skin and the liver is not the same so I don't know whether you know dermal patches are very effective for hormones at very low doses something is different about that so and the other thing not to forget is the mixture question so MEP exposure is correlated with MVP pretty highly and so I maybe we it's carried along those are the explanations I can suggest Paul and do you have anything to add I actually think you can go back to the literature you can look for dermal metabolism studies I mean I think there are some on the phthalates I can't honestly remember I don't remember them being markedly different in terms of it just strikes me as well you know I kind of agree with Shana is the largest concentration of phthalate that we find in any of our human studies you do wonder sometimes whether that's an index of exposure as much as it is an index of effect because it just seems to dominate a lot of the exposures that are seen in many of the human studies what the other points were now Paul when you say index of exposure you actually mean like a surrogate chemical exactly there is some literature on DEP studies I can send that to the committee I'll do this how old is it it's as old as the rest of the phthalate literature but it's multi-gen studies but you have to say doing a dermal multi-generation type study is a real challenge because almost certainly you can't avoid unless you're going to have big separation of the pups from the mum you're going to get grooming so that dermal is going to become an oral and you don't usually want to occlude young pups either that will be a very difficult study to do from the practical point of view this brings me to another point I think we have missed that one it's more relevant the peak concentration or the area under the curve because I think if we would consider the metabolism being the same we definitely have different time curves of resorption and elimination that's a difficult question answer based on the information we have but the studies that both Paul and I and other people have done where you do the high dose one day exposure that that type studies that he showed those are a lot less effective than exposure to even lower doses so they're clearly, I would say that if you're talking about the right, you'd want to inhibit you'd be more effective to inhibit fetal testosterone throughout the entire period of rat sex differentiation and just inhibit it for a day that's about inhibiting the hormone and not necessarily high or area under the curve I don't think that any of those probably know better have a half life long enough so that you wouldn't have bikes even with a daily dose I mean with hormones we know that some effects are driven by the peak height like the LH surge and ovulation and others are more obvious with chronic low levels the other way to look at that is when we compare the oral gavage studies which is a pulse once a day his dietary study and there really was very little difference there so one's much more continuous if you're the person who does the exposure you interpret that Donna, thank you for a very interesting presentation I have a couple questions yesterday I believe we saw some pie charts that indicated that the diet was the higher exposure route as opposed to dermal do you have data to show you dermal or I may have that incorrect in my mind but I thought several pie charts with diet diet diet okay so but when you do your studies do you have questionnaires about lifestyle care products we do and we find we've published one of these, we've published for the children we've published a study that the number of personal baby care products that's put on the baby is strongly correlated with measurable levels of several metabolites particularly MEP and baby urine we also and haven't published although Russ has published with men men's personal care products are correlated with their levels of MEP and MEP and we have the same thing for female we didn't publish it because it's known now and then there was a beautiful study from Denmark where they actually dose men a couple of men with measured levels of DPP and rubbed it all over them and measured it in their urine and there's a direct correlation there's no question that for those phthalates it's a dermal primarily but for DEHP and less to a lesser extent DPP but DEHP is primary and a holder can talk to that is food primarily okay so if you're thinking about a mixture then it would be a mixture is a mixture of your life you know I mean it's everywhere right so it's in your your car and it's in your hairspray it's in your food and it's in the plastics you use in your daily life your shower curtain and so on so on so if you're going to study a mixture you're going to get a reflection of the maybe I should just tell you that we have a study well I guess I shouldn't I guess I'll talk about that we have a study that actually gets at some of that what I'm trying to get to is if we're thinking about toys you know products for children right what's the universe relative to that in terms of exposures personal care products baby care products on the children or child care products, their foods if they're already well either through their breast milk or through their own food through and you know Bornehack studies on the indoor air what's on the floor so he found PVC on the flooring on the wall coverings varied and it seemed to there's a lot of sources and toys are one of them and of course there you have the dermal you know sucking on the toys and so on which might be an issue so I think for children you have to consider a total exposure as you do for adults so another question so it seems like from the animal studies we're focusing on reproductive developmental you've shown us some data on reproductive developmental but also on things like a little bit on metabolic syndrome type endpoints as well as behavior brain development in your mind do you have a ranking of what you think are the most important things to focus on for children or for humans or I'm a reproductive epidemiologist so for me reproduction and development are pretty key but the you know this fetal basis of adult disease model that's sort of in my head all the time that from DES and so on we know that those early exposures make huge differences throughout life so I think we're talking about I mean there's the question of the sensitive period and I think we all are agreement that the prenatal that nice male developmental window and perhaps for females we're just starting to learn you know it's very very critical but I think we can't avoid the risks from the nursing baby and nobody's mentioned because we don't have data on it but it's very important there's a surge in testosterone of three months in humans a hormonal surge called the mini puberty which I'm not allowed to stick our babies for blood at least our IRB doesn't want us to they could do it in Denmark but that's very interesting to see what how that would be altered by phthalates because that evidently sets up the male the brain program you know it affects the later sexual differentiation of the brain so I think there's just a lot of times during life that we should be concerned about these exposures that brings up a question Paul or Earl has anyone looked at whether phthalates can induce epigenetic changes? I'm not aware of any, I mean there were one or two studies with certain pesticides there were studies Mike Skinner has done studies with antiandrogens I asked him if he would look at DHP I don't know if he's doing that any other questions? what we'll do now is break for lunch and then we'll hear from you let's reconvene at 1.30 thank you all