H O R M O N E - M I M I C K I N G C H E M I C A L S What They Are, What They Do, and Where to Find Them A M B E R W I L L I A M S A N D D R . L A U R A H A K E R A R E L Y D O W E C O N S I D E R W H A T T H E C H E M I C A L S T H A T G O I N T O O U R C O N S U M E R P R O D U C T S , T H A T A R E S P R A Y E D O N T O O U R F R U I T S , O R T H A T A R E R E L E A S E D I N T O T H E A I R A C T U A L L Y D O . F O R E X A M P L E , W E A S S U M E T H A T T H O S E D I F FI C U L T - T O - R E A D C H E M I C A L S O N O U R S H A M P O O B O T T L E L A B E L S A R E S A F E . H O W E V E R , F E W O F T H E T H O U S A N D S O F C H E M I C A L S D E V E L O P E D E A C H Y E A R A R E T H O R O U G H L Y T E S T E D . F O R G O I N G T H E P R E C A U T I O N A R Y P R I N C I P L E , W E A R E E X P O S E D T O M A N Y C H E M I C A L S T H A T A C T A S E N D O C R I N E D I S R U P T O R S . E N D O C R I N E D I S R U P T I N G C H E M I C A L S ( E D C S ) C A N M I M I C , B L O C K , O R R E - R O U T E T H E H O R M O N A L S I G N A L I N G O F O U R B O D I E S . T H I S A R T I C L E A D D R E S S E S W H A T E D C S A R E , H O W T H E Y A C T , A N D H O W T H E Y C A U S E H A R M - F U L E F F E C T S , S U C H A S R E P R O D U C T I V E A B N O R M A L I T I E S , C A N C E R S , A N D B E H A V I O R A L C H A N G E S . F I N A L L Y , S T E P S T H A T W E A S C O N S U M E R S C A N T A K E T O A V O I D O R N E G A T E T H O S E E F F E C T S A R E E N U M E R A T E D . I N T R O D U C T I O N I n the twenty-f irst century, the use o f synthetic chemicals is an afterthought. T h o u g h not always desired, they are thor- oughly integrated i n t o daily l i fe . Embedded i n t o everything we touch , smel l , eat, and breathe, the prevalence o f these chemicals makes i t d i f f icul t to stop, take a step back, and as- sess the l o n g - t e r m effects. The d e m a n d for i m m e d i a t e con- venient i m p r o v e m e n t s , the encouragement o f technologi- cal advancements i n agr icul ture , manufacture , and medic ine , a n d the di f f iculty o f m o v i n g beyond the cancer p a r a d i g m m e a n that very few o f the thousands o f chemicals developed every year are tested for effects beyond toxicity. Therefore, m a n y o f the chemicals that go i n t o our products , l ike water bottles, per fumes, shampoos, a n d plastic toys may act as endocrine d isruptors , w h i c h m i m i c , block, or re- route the h o r m o n a l signals o f our bodies. Previous studies i n rodent and f i sh m o d e l organisms and h u m a n cell l ines have s h o w n that chemicals such as b i sphenol A and phtha- lates, w h i c h act as estrogens and antiandrogens respec- tively, increase occurrences o f cervical and prostate cancer, advance puberty, f emin ize males, increase reproductive organ m a l f o r m a t i o n s , and affect the integr i ty o f D N A . Together these studies provide the basis for a theory that the drastic decline i n h u m a n s p e r m count i n the last fifty years and the increasing n u m b e r o f reproductive organ abnor- mal i t ies , cancers, and allergies results, i n part , f r o m the use o f these chemicals that affect h o r m o n a l s ignal ing path- ways. E N D O C R I N E D I S R U P T O R S ! C H A R A C T E R I S - T I C S A N D M E C H A N I S M O F A C T I O N Endocrine d i s r u p t i n g chemicals (EDCs) interfere w i t h nor- m a l s ignal ing o f the body's intr icate h o r m o n a l networks . H o r m o n e s , b iochemica l messengers c o n t r o l l i n g m u c h o f the body's funct ions , act as the intermediar ies between sig- nals and actions. One part o f the body, such as the p i tu i ta ry g land, sends a message, l ike l u t e i n i z i n g h o r m o n e , to i l l i c i t an act ion i n another part o f the body, l ike s t i m u l a t i n g an ovary to release an egg. Examples o f h o r m o n e s range f r o m g r o w t h h o r m o n e s , w h i c h cont ro l development, to thyrox- ine , w h i c h helps manage m e t a b o l i s m , to i n s u l i n , w h i c h regulates b lood glucose levels, to the sex h o r m o n e s that ru le sexual development and reproduct ion . The body's del- icate h o r m o n a l balance necessitates signal consistency. The great complexi ty encompassed i n only the endocrine system is delicate and sensitive i n and o f itself, w i t h o u t ex- ternal influences such as EDCs. The h o r m o n a l pathway is complex at the cellular level. After t rave l ing t h r o u g h the b lood , a h o r m o n e m u s t interact w i t h a target cell . I f the h o r m o n e is a steroid, and therefore fat soluble, i t can cross the cell m e m b r a n e . Ins ide , i t b inds w i t h its c o m p l e m e n t receptor, w h i c h t h e n b inds to D N A w i t h i n the nucleus. Consequently, target genes are ex- pressed, leading to proteins that accompl ish the act ion specified a n d in i t i a ted by the o r i g i n a l s ignal . Examples o f these effects inc lude s t i m u l a t i o n or i n h i b i t i o n o f g r o w t h , i n d u c t i o n or suppression o f cell death, activation or i n h i b i - t i o n o f the i m m u n e system, regulat ion o f m e t a b o l i s m , preparat ion for physical activity, preparat ion for puberty, and cont ro l o f the reproductive cycle. Endocr ine disruptors m i m i c endogenous h o r m o n e s by b i n d i n g to the n o r m a l re- ceptors and subsequently t r i g g e r i n g an act ion even w h e n the actual h o r m o n e is n o t present. Endocr ine disruptors can also b lock essential s ignal ing by i n t e r f e r i n g w i t h the re- ceptor, in termediate molecules , enzymes, or t ransport pro- te ins . 1 I t is also possible for EDCs to alter the act ion alto- gether by, i n effect, g i v i n g the body "new" or distorted i n s t r u c t i o n s . 1 1 Fat-insoluble h o r m o n e s a n d EDCs tr igger actions ins ide the cell by b i n d i n g externally to receptors o n the cell m e m - brane. T h r o u g h a series o f conformat iona l changes, the re- ceptor init iates signal t ransduct ion , a type o f relay between m u l t i p l e molecules w i t h i n the cell . The s ignal ing molecule thus elicits an act ion that is n o t only ampl i f i ed thousands o f t imes compared to the o r i g i n a l signal, b u t also occurs i n m u c h less t i m e t h a n i t takes for genes to be expressed. E N D O C R I N E D I S R U P T O R S A C T U N D E R T H E R A D A R Chemica l test ing methods have t radi t ional ly focused o n as- E L E M E N T S S P R I N G 10 sessing acute toxicity, reflected by m o r t a l i t y or p o i s o n i n g o f test animals . Based o n the a s s u m p t i o n that "the dose makes the po ison , " chemical test ing is s t i l l focused o n tox- icity at relatively h i g h concentrations. G r a p h i n g toxicity test results is expected to produce a l inear dose response curve, w i t h h igher response corresponding to increased dosage. Chemicals approved for use i n consumer prod- ucts, o f course, show a negl ig ible toxic effect at h i g h con- centrations, leading scientists to presume that these chem- icals are not h a r m f u l at any concentrat ion. To the contrary, the newly recognized class o f EDCs has p r o f o u n d deleteri- ous effects at doses hundreds , or even thousands, o f t imes lower t h a n supposedly "safe" concentrations d e t e r m i n e d by classic toxicity test ing. As EDCs can i n t e r r u p t h o r m o n a l pathways at t i n y doses o f parts per m i l l i o n , or even parts per b i l l i o n , daily exposure to seemingly inconsequent ia l amounts o f EDCs can lead to drastic effects. M a n y EDCs actually el icit a "U-shaped" dose response curve. I n other words , some EDCs at very l o w a n d very h i g h concentrations may n o t show as s trong an effect as expo- sures to EDCs at concentrations somewhere i n the m i d d l e , or conversely, the m i d d l e doses may n o t have as great an ef- fect as l o w and h i g h doses. Assessment o f the hazards o f EDCs is also compl icated by the fact that the i r effects are n o t as acute as o u t r i g h t p o i s o n i n g a n d are usual ly not ob- served i m m e d i a t e l y after exposure. 1 " Therefore, fetal expo- sure may n o t result i n any apparent consequences u n t i l later i n adul thood, w i t h onset o f i n f e r t i l i t y problems , can- cers, a n d behavioral abnormal i t ies . B I S P H E N O L A Bisphenol A (BPA) is an EDC that acts as an estrogen m i m i c . I n 2 0 0 4 , the U n i t e d States alone produced about one m i l l i o n tons. As an ingred ient i n polycarbonate plas- tics, BPA gives the characteristic o f durabi l i ty . T h u s , poly- carbonate is used to make baby bottles, water bottles, toys, and medica l devices. BPA can also be f o u n d i n the epoxy resins that coat the inside o f food and beverage cans and i n dental sealants. 1 V I n h u m a n s , BPA has been measured i n a m n i o t i c fluid, materna l and fetal plasma, and placental tis- sue at b i r t h . v Due to the n u m e r o u s ways that BPA infi l trates daily l i fe , there are s ignif icant concerns that exposure to BPA at the levels f o u n d i n adults, and especially i n the developing fetus ( w h i c h has an under-developed abi l i ty to remove BPA), has l o n g - t e r m adverse hea l th consequences. These concerns are based o n hundreds o f studies u s i n g a n i m a l m o d e l a n d tissue cu l ture systems that demonstrate effects o f BPA at levels equivalent to , a n d even lower t h a n , the lev- els detected i n h u m a n b lood a n d u r i n e (Table 1). A study u s i n g BPA doses below w h a t the EPA's safety guidel ines f o u n d that BPA ( i n c o n j u n c t i o n w i t h i n s u l i n ) tr iggers the f o r m a t i o n o f fat cells i n mice . After eleven days, w i t h BPA exposure i n only the f irst t w o days, fat con- tent i n the cells increased by 150 percent compared to con- trols . W h e n the cells were exposed to BPA for 11 f u l l days, there was a 1,300 percent increase i n fat c o n t e n t / 1 S imi lar f indings f r o m other research groups, coupled w i t h measur- able levels o f BPA and a host o f other EDCs i n h u m a n s , have raised concerns o f a causal l i n k between bodi ly EDC levels, also k n o w n as body b u r d e n , a n d the current obesity e p i d e m i c / 1 1 Contaminants and viruses can work together. E L E V A T E D L E V E L S O F P S B S A N D E P S T E I N B A R R V I R U S I N C R E A S E T H E R I S K O F N O N - H O D G K I N ' S L Y M P H O M A BY O V E R 2 0 - F O L D . v i » H O R M O N E - M I M I C K I N G C H E M I C A L S T A B L E 1: B P A E X P O S U R E IN A N I M A L S T U D I E S DAILY BPA EXPOSURE .(^.^.^ .?P.P.Y. w E J H T - D A Y ) X.7??fA :̂. .T^.^.T^X ?JU.PY DETAILS REFERENCE PERSISTENT CHANCES TO BREAST TISSUE, 0.025 PREDISPOSES CELLS TO H O R M O N E S A N D CARCINOGENS FETAL EXPOSURE, CHANCES NOTED AT 6 M O N T H S OF ACE M U N O Z - D E - T O R O 2005 0.025 PERMANENT CHANCES TO GENITAL TRACT FETAL EXPOSURE MARKEY 2005 2 INCREASED AGGRESSION AT 8 WEEKS OF LIFE FETAL EXPOSURE, ORAL ROUTE KAWAI 2003 2.4 DECLINE IN TESTICULAR TESTOSTERONE FETAL AN D N EON ATAL EXPOSU RE, GAVAG E A R K I N G B E M I 2004 2.5 I M M U N E SYSTEM IMPACTS ORAL EXPOSURE SAWA|2003 10 PROSTATE CELLS MORE SENSITIVE TO H O R M O N E S A N D CANCER FETAL EXPOSURE, ORAL ROUTE, SHORT DURATION T I M M S 2005 I N S U L I N RESISTANCE DEVELOPS IN 2 DAYS, C H R O N I C HYPER! N- 10 S U L I N E M I A AT DAY 4 SU BCUTAN EOUS IN) ECTI O N , S H O RT DU RATI O N EX POS U R E A L O N S O - M A C D A L E N A 2006 20 DAMAGE TO EGGS A N D C H R O M O S O M E S FETAL EXPOSURE, OSMOTIC PUMPS H U N T 2003 REVERSED THE N O R M A L SEX DIFFERENCES IN BRAIN STRUCTURE 30 A N D BEHAVIOR O RA L DU Rl N G C ESTATION A N D LACTATIO N KUBO 2001 30 HYPERACTIVITY ORAL I S H I D O 2004 EPA'S "SAFE EXPOSURE LEVEL," BASED O N OUTDATED, H I G H DOSE STUDIES 50 EPA RFD (REFERENCE DOSE) A N D A 1000-FOLD M A R G I N OF SAFETY EPA 1998 T A B L E 2: E N D O C R I N E D I S R U P T O R S IN C O N S U M E R P R O D U C T S T A B L E 3: W E B S I T E S O N A V O I D I N G E D C S ENDOCRINE RECEPTOR USED AS F O U N D IN ACTS AS L I N K E D TO TITLE DESCRIPTION WEBSITE B I S P H E N O L A EPOXY RESINS OF HARD PLASTIC WATER ESTROGEN CANCER/TREATMENT T H E C A M P A I G N FOR SAFE A I M S "TO PROTECT T H E H E A L T H OF WWW.SAFECOSMETICS.ORG CANS, POLYCARBON- BOTTLES, PLASTIC RESISTANCE, F E M I - COSMETICS CONSUMERS A N D WORKERS BY REQUIR- ATE PLASTICS, DENTAL TOYS N I Z A T I O N / M A S C U L I N - I N G T H E PERSONAL CARE PRODUCTS SEALANTS Z A T I O N , D N A INDUSTRY TO PHASE O U T T H E USE OF INTEGRITY CHEMICALS L I N K E D TO CANCER, BIRTH DEFECTS A N D OTHER SERIOUS HEALTH CONCERNS, A N D TO REPLACE T H E M W I T H SAFER ALTERNATIVES." PHTHALATES PLASTICIZER, N A I L P O L I S H , PER- A N T I - A N D R O C E N MALE G E N I T A L S K I N DEEP "A SAFETY G U I D E TO COSMETICS A N D WWW.COSMETICSDATABASE.COM FRAGRANCES FUMES, PLASTIC A B N O R M A L I T I E S , PERSONAL CARE PRODUCTS B R O U G H T SHOWER CURTAINS MALE INFERTILITY TO Y O U BY RESEARCHERS AT T H E E N V I - ( L O W SPERM C O U N T ) R O N M E N T A L W O R K I N G GROUP." PARABENS PRESERVATIVE I N COS MOISTURIZERS, ESTROGEN BREATS CANCER, RE- W O M E N ' S HEALTH A N D T H E A WEBSITE T H A T "EXPLAINS WAYS T H A T W W W . W O M ENSH EALTH AN D E N - METICS & P H A R M A - S H A M P O O S P R O D U C T I O N A B N O R - E N V I R O N M E N T O U R HEALTH CAN BE AFFECTED BY E N V I - V I R O N M E N T . O R G CEUTICALS MALITIES/ INFERTILITY R O N M E N T A L C O N T A M I N A N T S A N D OF- FERS IDEAS OF H O W T O MAKE CHANGES A R O U N D YOUR H O M E A N D I N YOUR C O M M U N I T Y SO WE CAN LIVE I N A HEALTHIER WORLD." LEAD P I G M E N T LIPSTICK, DARK H A I R N E U R O T O X I N C O G N I T I V E REDUC- GREEN G U I D E FOR EVERYDAY PROVIDED BY N A T I O N A L GEOGRAPHIC, W W W . T H E G R E E N G U I D E . C O M / B U DYES T I O N , DELAYED PU- L I V I N G I N F O R M A T I O N COVERING A RANGE Y I N G - G U I D E BERTY FROM CARPETS TO C L E A N I N G PROD- UCTS TO SUNSCREEN. http://WWW.SAFECOSMETICS.ORG http://WWW.COSMETICSDATABASE.COM http://WWW.WOM http://VIRONMENT.ORG http://www.thegreenguide.com/bu I n a related study, scientists f o u n d a corre lat ion between h i g h u r i n a r y BPA concentrations and b o t h cardiovascular disease and diabetes i n h u m a n s . i x I n add i t ion , m i c e ex- posed to BPA t h r o u g h damaged polycarbonate cages and water bottles (by n o r m a l wear and tear) led to meiot ic ane- uploidy, or an incorrect n u m b e r o f chromosomes present i n the cells that develop i n t o eggs. These observations and s imi la r studies indicate that h u m a n exposure to BPA may inc i te n u m e r i c a l c h r o m o s o m a l abnormal i t ies , the leading causes o f miscarriage, congenita l defects, and m e n t a l retar- d a t i o n ^ BPA exposure has been l i n k e d to cancers, i n c l u d i n g breast and prostate cancer. Pregnant rats treated w i t h 25 m c g / k g body we ight per day gave b i r t h to daughters that showed p e r m a n e n t l y altered m a m m a r y glands w i t h cell proli fera- t i o n a n d an increase i n susceptibi l i ty to a tested carcino- g e n . x l I n effect, cells became sensitized by BPA to respond to a carcinogen even before b i r t h . I n the U n i t e d States, prostate cancer is the second leading cause o f cancer death a m o n g m e n and the leading diagnosed m a l i g n a n c y . x i l Prostate cancer depends o n testosterone for g r o w t h , so t reatments focus o n testosterone depr ivat ion either t h r o u g h i n h i b i t i o n o f testosterone synthesis or by blockage o f the testosterone receptor. Th i s type o f t reatment is suc- cessful for u p to 18 to 30 m o n t h s w h e n recurrent t u m o r s develop i n some p a t i e n t s . x i l i G r o w t h o f recurrent t u m o r s can be s t imulated by a variety o f mechanisms . I n one study, 25 percent o f the recurrent t u m o r s h a d acquired a m u t a t i o n i n the testosterone receptor that changed the shape o f the testosterone-binding site. Therefore, a l though the ablat ion therapy h a d removed al l testosterone f r o m the patients ' bodies, the t u m o r s were sensitive to s t i m u l a t i o n by other compounds , i n c l u d i n g estrogen and B P A . x i v Essentially, BPA can b i n d to the m u t a t e d receptor and s t imulate cell g r o w t h a n d pro l i fe ra t ion , events n o r m a l l y s t imulated by testosterone, thus advancing the prostate cancer. BPA exposure also interferes w i t h sex specific development o f the body and b r a i n . BPA i n only parts per b i l l i o n has been s h o w n to mascul in ize areas o f the female b r a i n . The development o f the area o f the b r a i n responsible for estrous cyclicity, gonadotrop in release, and the l u t e i n i z i n g hor- m o n e surge necessary for ovulat ion is di f ferent i n male and female rats. However, i n pregnant rats exposed to BPA, the daughters ' brains began to resemble those o f males, a n d the daughters exhibited mascu l in ized behavior. Th i s study shows that BPA can cross the placental barr ier and that the fetus is extremely sensitive to exposure, leading to longer- last ing effects. x v Addit ional ly , pregnant rats exposed to BPA h a d daughters w i t h accelerated puberty. I n fact, endocr ine-d is rupt ing chemicals may be one o f the causes o f the global t r e n d o f earlier sexual m a t u r a t i o n i n g i r l s . x v i I n the U n i t e d States, gir ls b e g i n m e n s t r u a t i o n a few m o n t h s earlier t h a n they d i d 4 0 years ago and develop breasts 1-2 years ear l i e r . x v i i Puberty at a younger age has been l i n k e d to an increased r i sk for depression, obesity, polycystic ovarian syndrome, breast cancer, and ovarian cancer . x v i l i Social prob lems such as an increased r i sk o f sexual v i c t i m i z a t i o n and exper imen- t a t i o n w i t h sex, alcohol, or drugs may become m o r e l ike ly at an earlier age . x i x Earlier puberty may also lead to addi- EDCs can increase immune responses and allergic reactions.x x S I N C E 1980 A S T H M A D E A T H R A T E S F O R C H I L D R E N Y O U N G E R T H A N 19 Y E A R S O L D H A V E I N C R E A S E D BY A L M O S T S0%.xxi T H E P R E V A L E N C E O F P E A N U T A L L E R C I ES D O U B L E D IN T H E 5 Y E A R S F R O M 1997 T O 2002.**" C H I L D R E N W I T H E L E V A T E D L E V E L S O F C O N T A M I - N A N T S A R E 8 X M O R E L I K E L Y T O H A V E C H I C K E N P O X A N D 3X M O R E L I K E L Y T O H A V E 6 0 R M O R E EAR I N F E C T I O N S BY T H E A C E O F 3 1 / 2 . x x i i i H O R M O N E - M I M I C K I N G C H E M I C A L S t i o n a l physical and behavioral problems later i n l i fe due to longer exposure to h o r m o n e s . BPA can interact w i t h b o t h cell m e m b r a n e and i n t e r n a l cel- lu lar receptors. For example, BPA interacts w i t h cell m e m - brane receptors and increases pro lac t in secretion f r o m cells. Increased pro lact in can lead to a decrease i n fert i l i ty , cell pro l i fe ra t ion , behavioral effects, and interference w i t h o v u l a t i o n . 5 0 ^ BPA also interacts w i t h b o t h types o f pancre- atic cell receptors. I n effect, these cells rapidly release i n - s u l i n i n t o the b loodstream to decrease glucose levels. W i t h longer exposures to BPA, the cells secrete too m u c h i n - s u l i n , w h i c h eventually leads to i n s u l i n resistance. I n other words , target cells no longer uptake glucose i n response to i n s u l i n because the signal is constant a n d the cell is n o longer sensitive to i t . Therefore, exposure to e n v i r o n m e n - tal estrogens can enhance the r i sk o f developing type 2 dia- betes, hypertens ion, and a b n o r m a l levels o f fats i n the b l o o d . ™ O T H E R E D C S Other chemicals act by m i m i c k i n g or b l o c k i n g testos- terone. Some, l ike v i n c l o z o l i n (a fungic ide) , demascul inize male rats, exempli f ied by a decreased anogenital distance ( A G D ) , reta ined nipples , hypospadias, and absent sex ac- cessory g l a n d s . ™ 1 Phthalates are another class o f testosterone-blocking chem- icals used as plasticizers i n products such as food contain- ers, toys, medica l e q u i p m e n t , and shower curtains . Perfumes, hairspray, cosmetics, and the new car smel l can also conta in phthalates. The t e r m "phthalate syndrome" has been coined to describe genital abnormal i t ies that are a result o f exposure to phthalates, i n c l u d i n g undescended testicles. A h u m a n study conducted by the Centers for Disease Contro l , Harvard School o f Public Hea l th , the Dana Farber Cancer Ins t i tu te , and Harvard Medical School examined the corre lat ion between phthalate levels i n u r i n e samples and various sperm parameters i n 168 m e n . Semen samples were analyzed for s p e r m count , sperm m o t i l i t y , and the percentage o f de formed sperm. A total o f Hypospadia THE FREQUENCY RATE FOR HYPOSPADIA HAS MORE THAN DOUBLED SINCE 1970. I N 1993, 1 OF EVERY 125 BOYS WAS AFFECTED.**™ Sperm Count THE SPERM COUNT FOR THE AVERAGE MALE I N 1938 WAS 113 M I L L I O N / M L . THE SPERM COUNT FOR THE AVERAGE MALE IN 1990 WAS 66 M I L L I O N / M L , A 50% DECLINE IN APPROXIMATELY 50 Y E A R S . * * ™ " Sex Ratio THERE IS CURRENTLY A DECREASE OF 1 MALE BIRTH IN 1000 LIVE BIRTHS WHICH RESULTS I N A LOSS OF APPROXIMATELY 38,000 MALE BABIES I N 20 YEARS I N THE UNITED STATES.50"* Hypospadia A M A L E B I R T H D E F E C T IN W H I C H T H E O P E N I N G O F T H E U R E T H R A , U S U A L L Y A T T H E T l P O F T H E P E N I S , IS A B N O R M A L L Y P L A C E D ( O P E N I N G S O M E - W H E R E A L O N G T H E S H A F T ) . Anogenital Distance T H E D I S T A N C E O F T H E P E R I N E U M ( B E T W E E N T H E A N U S A N D T H E B A S E O F T H E P E N I S F O R A M A L E ) . T H E A G D IS T W I C E AS L O N G IN M A L E S T H A N F E - M A L E S , S O T H E M E A S U R E IS U S E D IN N E O N A T A L H U M A N S T O C O R R E L A T E F E M I N I Z A T I O N ( R E P R O - D U C T I V E A B N O R M A L I T I E S ) T O C O N T A M I N A N T B L O O D O R U R E A L E V E L S . E L E M E N T S S P R I N G 1 eight di f ferent phthalate metabolites were f o u n d i n the u r i n e samples. M e n w i t h h i g h levels o f the d i b u t y l phtha- late metabol i te were m o r e t h a n twice as l ike ly to have l o w sperm m o t i l i t y t h a n m e n w i t h l o w levels o f the metabol i te . H i g h levels o f other phthalates were also l i n k e d w i t h re- duced sperm count a n d a h igher percentage o f de formed sperm. T h i s study reveals the connections between phtha- late levels i n the A m e r i c a n male p o p u l a t i o n and i m p a i r e d s p e r m qual i ty and q u a n t i t y . 5 0 0 ' Similarly, studies have indicated w o r l d w i d e d e c l i n i n g s p e r m counts. A review o f 61 studies pub l i shed i n 1992 discovered that the average male s p e r m count dropped f r o m 113 m i l l i o n / m l i n 1938 to 6 6 m i l l i o n / m l i n 1 9 g o . 5 0 ™ A change th is drastic i n such a short t i m e per iod cannot be solely genetically d e t e r m i n e d , so the answer most l ike ly lies i n e n v i r o n m e n t a l influences. There are n u m e r o u s theories concern ing the s p e r m count decline, one b e i n g the involve- m e n t o f EDCs, especially since w o m e n o f ch i ldbear ing age are one o f the groups w i t h the highest exposure l e v e l s . ™ 1 Exposure to endocr ine disruptors affects w i l d l i f e as w e l l . I n an isolated lake ecosystem, f i sh populat ions exposed to the synthetic estrogen f o u n d i n b i r t h cont ro l p i l l s collapsed due to f e m i n i z a t i o n o f males. Arrested testicular development and subsequent reduced fer t i l i za t ion success led to a near ext inct ion o f the fathead m i n n o w i n the lake. Therefore, low-level, consistent exposure has the ecological r i sk o f dis- r u p t i n g the sustainabil i ty o f w i l d p o p u l a t i o n s . x x x [ i i I M P O R T A N C E The scope o f the damage endocr ine d i s r u p t i n g chemicals have caused and the i r potent ia l for damage i n the future ne- cessitates awareness. Instead o f accepting the potent ia l danger, or c o n d e m n i n g all chemicals as dangerous i t is i n - stead i m p o r t a n t to regulate exposure i n order to reduce the effects. There are over 8 0 , 0 0 0 chemicals registered w i t h the U.S. E n v i r o n m e n t a l Protect ion Agency, approximately 3 ,000 labeled as h i g h p r o d u c t i o n v o l u m e (accounting for 9 9 percent o f the total v o l u m e ) , w i t h at least one m i l l i o n pounds produced or i m p o r t e d i n the U . S . x x x i v O f these 3 ,000 h i g h p r o d u c t i o n v o l u m e chemicals , 43 percent have n o basic toxicity test ing data available to the pub l i c and only 7 percent have the f u l l basic test ing in format ion . 5 0 0 ™ Each chemical has six basic tests specified and w i t h a cost o f $205 ,000 per chemical , i t w o u l d cost the chemica l indus- try approximately $427 m i l l i o n to complete the basic test- i n g o f the h i g h p r o d u c t i o n v o l u m e chemicals. T h o u g h this is a h i g h expense, an a r g u m e n t that the chemical i n d u s t r y pleads frequently, i n reality, i t is only 0.2 percent o f the an- n u a l sales o f the top h u n d r e d chemica l i n d u s t r i e s . x x x v i Aside f r o m these basic tests, n o chemical has been ade- quately tested for endocr ine d i s r u p t i o n . A c t i o n w i l l require policy changes to ensure the sustainabil i ty o f l i fe o n earth. Most Amer icans assume that chemicals used i n products are safe; however, u n l i k e the d r u g industry , the government has to prove that a chemical is h a r m f u l , rather t h a n requir- i n g the manufacturers to prove that i t is safe before u s e x x x v n j l v i s protocol , a long w i t h unenforced test ing, lends to an unregulated chemica l i n d u s t r y and the use o f Teflon, used as a non-stick coating for cookware, can emit toxic particles. IN 2-5 Ml N, TEFLON-COATED COOKWARE CAN REACH TEMPERATURES AT W H I C H THE COATING BREAKS A N D EMITS TOXIC PARTICLES AND GASES LINKED TO HUNDREDS (MAYBE THOUSANDS) OF PET BIRD DEATHS AND AN U N K N O W N NUMBER OF H U M A N ILLNESSES EACH YEAR.***"'" H O R M O N E - M I M I C K I N G C H E M I C A L S inadequately tested chemicals i n consumer products . Increased test ing p r i o r to sale w i l l require the development o f an appropriate procedure because current test ing for en- docr ine-d i s rupt ing abil it ies is convoluted, t ime-consum- i n g , and varies between testers. A c o m m i t m e n t by b o t h the government and the chemical i n d u s t r y to safeguard the hea l th o f h u m a n i t y is absolutely necessary. Recently, the Lowel l Center for Sustainable Product ion and the Toward T o m o r r o w Ini t ia t ive released "A C o m m o n Agenda for H e a l t h and the E n v i r o n m e n t , " i n w h i c h they "seek to help shift the debate about l i n k s between e n v i r o n m e n t and heal th f r o m a focus o n w h i c h materials and substances cause w h i c h problems , to a discussion about what k i n d o f w o r l d we want to l ive i n a n d h o w we get t h e r e . " 5 0 0 ™ Reflecting these ideals is the development o f "green chem- istry," w h i c h reduces waste, uses materials f r o m sustain- able sources, and tries to design chemicals that are less haz- ardous ( in the short a n d l o n g t e r m ) to h u m a n heal th . n o w c o m m o n knowledge that BPA is f o u n d i n plastic baby bottles. However, i n the U n i t e d States there is n o nat iona l law regu la t ing BPA i n the bottles that feed the youngest, most susceptible cit izens. Instead, e l i m i n a t i o n o f BPA is d e t e r m i n e d o n a state-by-state level. Cal i fornia has passed Senate B i l l 578, that "requires manufacturers o f H i g h Product ion V o l u m e chemicals to provide to the state infor- m a t i o n re lat ing to whether a chemical causes or has the po- tent ia l to cause cancer, reproductive h a r m , neurologica l damage, respiratory h a r m , endocr ine d i s r u p t i o n or devel- o p m e n t a l h a r m . " x l n Also , Connect icut has banned BPA f r o m in fant f o r m u l a and baby food cans and j a r s . x ' 1 " O n the other h a n d , Massachusetts pub l i c hea l th officials have only issued a w a r n i n g to mothers to avoid baby products con- t a i n i n g BPA. No official regulat ions have been passed . x l i v Startlingly, a recent study p e r f o r m e d by H e a l t h Canada re- por ted that "BPA-free" baby bottles were i n reality s t i l l l eaching BPA, w h i c h fur ther stresses the need for adequate The FDA does not regulate what goes into cosmetics. 61% OF 33 BRAND-NAME LIPSTICKS TESTED BY THE CAMPAIGN FOR SAFE COSMETICS CONTAINED DETECTABLE LEVELS OF LEAD.*' ENVIRONMENTAL WORKING GROUP MEASURED 16 CHEMICALS FROM 4 CHEMICAL FAMILIES (PHTHALATES, TRICLOSAN, PARABENS, AN D M U S KS) I N TH E BLOOD AND URINE SAMPLES OF 20 TEEN G I RLS OF AG ES 1 4 TO ~\9.xli Fur thermore , development and i m p l e m e n t a t i o n o f pol icy and regulat ions to remove demonstrated endocr ine d isrup- tors is p a r a m o u n t . I n the s u m m e r o f 2 0 0 8 , pub l i c aware- ness regarding BPA i n Nalgene water bottles j u m p e d , a n d subsequently, BPA was removed f r o m these products . However, removal o f endocr ine disruptors i n products is current ly u p to the companies and consumer pressure, rather t h a n any regulatory enforcement. For example, i t is test ing and transparency w i t h i n the chemical i n d u s t r y . x l v O f course, obstacles s t i l l exist due to the n u m b e r o f prod- ucts to regulate and incomplete ingred ient lists due to "trade secrets." Yet, t h r o u g h research, we can become i n - f o r m e d a n d consequently, can act. P R O T E C T I N G Y O U R S E L F One o f the m o s t t r o u b l i n g aspects o f EDCs is the i r ubiqui ty . E L E M E N T S S P R I N G 10 F r o m h u m a n s to animals , i n the city or the Arct ic , they are p r e v a l e n t x l v l Equally o m i n o u s , h u m a n s are exposed to a m i x t u r e o f these chemicals constantly, n o t just one at a t i m e or i n a single dose. Exposure comes f r o m the air we breathe, the grass we w a l k o n , the foods we eat, and the products we apply to our sk in . Studies l o o k i n g at the way some o f these chemicals w o r k together show that they can enhance effects i n a dose-additive or synergistic w a y x l v n , x lv i i i p o r example, 35 percent o f f rog tadpoles ex- posed to a m i x t u r e o f n i n e pesticides d ied due to a bacterial in fec t ion , compared to 4 percent fatality w h e n exposed to a single pesticide. I n add i t ion , 70 percent o f the mixture-ex- posed tadpoles that survived developed infect ions, seen i n none o f the controls or tadpoles exposed to one p e s t i c i d e . x l l x Also, EDCs do n o t share s t ructura l mot i f s , w h i c h makes the i r modes o f act ion unpredictable . Since one chemical can act i n n u m e r o u s ways o n m u l t i p l e systems, our future i n re la t ion to these synthetic chemicals is entirely uncer- ta in . Current ly , protect ion f r o m endocrine disruptors means avoid ing the i r sources. For example, plastics w i t h n u m b e r s 3, 6, a n d 7 conta in chemicals that are k n o w n to be EDCs. Plastic labeled "#7" is f requently polycarbonate plastic, a n d t h r o u g h n o r m a l use, the plastic can suffer wear a n d tear, causing the BPA to leach out i n t o l iqu ids or food. S imply s w i t c h i n g to a non-polycarbonate d r i n k i n g water bott le can rapidly decrease the levels o f BPA i n b l o o d and u r i n e , s h o w n by a study w i t h 77 part ic ipants i n w h i c h u r i n e levels o f BPA increased by 6 9 percent after u s i n g a polycarbonate water bott le compared to one week d r i n k i n g cold beverages f r o m a stainless steel water bott le instead. 1 M i c r o w a v i n g i n plastic is also dangerous as extreme heat causes plastic to lose its integrity , w h i c h results i n chemica l leaching. Personal care products are another source o f exposure, and reading labels can a id i n reduc ing r isk. A v o i d i n g phtha- lates, parabens, and fragrances, a n d u s i n g the Sk in Deep cosmetics database is the best way to secure products w i t h m i n i m a l or l o w risks. Plus, exposures i n a parent's body can show u p i n u n b o r n c h i l d r e n . A d o p t i n g precautionary pr inc ip les w i l l he lp decrease exposure to chemicals that are assumed to be safe, b u t may be labeled otherwise i n 30 years. A n u n k n o w n chemica l o n a label w i t h u n k n o w n ef- fects and l i t t le background i n f o r m a t i o n available should be avoided. I t is n o t i n s u r e d that companies are proper ly test- i n g and m o n i t o r i n g the publ ica l ly d i s t r i b u t e d chemicals . Dust-free houses are also safer as chemicals can reside i n dust and can be m a i n t a i n e d for a l o n g t i m e , a c c u m u l a t i n g and sensi t iz ing the body. Phthalates f o u n d i n dust samples have been l i n k e d to an increased incidence o f allergic reac- t ions i n ch i ldren , l ike asthma a n d eczema. 1 1 Protect ion f r o m EDCs is cr i t ica l , b u t l i v i n g i n the chemical- laden twenty-f irst century makes completely avoiding EDCs imposs ible . Therefore, r e m o v i n g endocr ine d isrup- tors f r o m our products , food, and air depends o n advocat- i n g for change. Endocr ine d isruptors should n o t be i n shampoos, f u r n i t u r e , and f ru i t s . Because current test ing methods and safety standards are n o t u p to date and chem- ical companies lobby government regulatory departments , a consumer response is necessary. Fortunately, pub l i c knowledge about endocrine disruptors is increasing. The n a i l po l i sh l i n e O P I advertises b e i n g phthalate-free, the l i n e Yes To Carrots provides paraben-free toi letr ies , and phtha- lates were out lawed f r o m chi ldren's plastic toys i n February 2 0 0 9 . 1 1 1 P R O T E C T I N G Y O U R F U T U R E As previously m e n t i o n e d , a c h i l d developing i n the w o m b is extremely susceptible to e n v i r o n m e n t a l inf luences. A single fert i l ized cell developing i n t o an o r g a n i s m made u p o f t r i l l i o n s o f cells is a staggering process aided by i m - mensely complex s ignal ing. I n the t h i r d week after concep- t i o n , the fetus is f o r m i n g the or ig ins o f the b r a i n , spinal cord, heart, a n d other organs. Cells m u s t c o m m u n i c a t e i n - struct ions w i t h one another o n where to go, w h a t to be- come, w h e n to divide, and w h e n to die. A l l o f th is depends u p o n relayed messages, m a n y o f t h e m chemical . I f en- docrine disruptors become another c o m p o n e n t i n a chi ld 's gestation per iod , the consequences can be m o n u m e n t a l . I t is k n o w n that d r i n k i n g alcohol or s m o k i n g w h i l e pregnant H O R M O N E - M I M I C K I N G C H E M I C A L S poses m a j o r threats to the n o r m a l development (physically, mental ly , and behaviorally) o f a c h i l d , and endocrine dis- rupters can be just as dangerous. Effects can show t h e m - selves directly at b i r t h , w i t h genital abnormal i t ies or i m - m u n e deficiencies. Cognit ive abnormal i t ies or allergies may become apparent later, a n d results may even only show u p i n adul thood, w i t h cancers, obesity, diabetes, a n d i n f e r t i l i t y prob lems . A l a r m i n g l y , the parent a n d developing fetus are n o t solely affected by exposure. Endocr ine disruptors also inf luence the fetus' g e r m l i n e cells. G e r m cells eventually develop i n t o the eggs or s p e r m cells o f a c h i l d . Therefore, an ex- posed m o t h e r can inadvertent ly r i sk the n o r m a l develop- m e n t o f her g randch i ldren as we l l . Studies have s h o w n that endocrine disruptors can interfere w i t h genetic i m p r i n t i n g i n rats. I m p r i n t i n g o f D N A is a s t ructura l m o d i f i c a t i o n that can either a l low or i n h i b i t gene expression and can be passed d o w n t h r o u g h the g e r m cells. Future generations can s t i l l exhibi t effects due to the exposure o f great-grand- parents . 1 1 1 1 These changes i n the structure o f D N A i t se l f can lead to adult-onset disease, such as t u m o r s , k idney dys- f u n c t i o n , and other problems l ike i m m u n e abnormal i t ies and premature a g i n g . l l v I n a d d i t i o n to the potent ia l for EDCs to cause p e r m a n e n t changes i n the developing fetus and its g e r m l i n e , some EDCs are passed directly to the baby as "hand-me-down poisons." M a n y synthetic chemicals are l i p i d soluble a n d can accumulate i n fat indef initely . One such transfer can occur w i t h breast m i l k . Endocrine disruptors are stored w i t h i n the fatty tissue o f the breast and t h e n excreted t h r o u g h breastfeeding. BPA has been measured i n the range o f 0.2-5.0 n g / m l o f breast m i l k , w h i c h under l ines that exposure can come f r o m m a n y dif ferent sources. l v W h e t h e r i t is the pregnant mother ' s products , or her ch i l - dren's toys, awareness o f these dangerous chemicals and h o w they play an integra l part i n our daily lives is crucial . C O N C L U S I O N Research regarding endocr ine d i s r u p t i n g chemicals is n o t just for scientists. I t is n o t knowledge just for doctors, or lawyers, or m o m s , or even only h u m a n s . The changes that we are seeing i n reproductive organs, i n a n i m a l behavior, and i n the rises o f allergies and obesity are systems-level prob lems that need to be addressed i n a t ransdisc ip l inary way. Endocr ine d i s r u p t i n g chemicals are n o t the sole cause o f any o f these problems , b u t they undoubted ly contr ibute . I t is i m p o r t a n t to r e m e m b e r that h u m a n s are b o t h b io log i - cal and cu l tura l organisms embedded i n social and ecolog- ical systems. l v i EDCs, w h i c h p u t h u m a n reproductive suc- cess at r i sk , affect us b o t h as a biological species a n d the way we w i l l have to respond socially. T h i n k i n g about h u - m a n s as agents act ing w i t h i n socio-ecological systems rather t h a n external drivers w i l l lead to m o r e global, long- last ing s o l u t i o n s . l v l 1 Th i s crisis begins at a personal , i n t i - mate level i n regards to one's o w n body and extends to a global crisis o f the h u m a n race and life o n earth altogether. Recognizing the potent ia l for h a r m a n d s u p p o r t i n g re- search concern ing the l o n g - t e r m effects o f endocr ine dis- ruptors w i l l lead to awareness, recogni t ion , and pol i t ica l ac- t i o n i n order to protect ourselves and future generations. E N D N O T E S i . 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