Less than or equal to 0.4 m g /cu m Less than or equal to 2.0 m g /c u m Less than or equal to 40 m g /cu m 40 m g /cu m or greater or unknown ( 1 ) H alf-m ask respirator with high-efficiency filter (s). ( 2 ) T ype C dem and-type (n eg ative pressure) supplied-air res pirator with half-m ask facepiece. (1 ) F ull facepiece respirator w ith high-efficiency filter (s). ( 2 ) T ype C dem and-type (n eg ative pressure) supplied-air res pirator with full facepiece. (3 ) Self-contained breathing ap paratus with full facepiece in de mand m ode (negative pressure). ( 1 ) Pow ered air-purifying (p osi tive pressure) respirator with high efficiency filter(s). (2 ) T ype C continuous-flow (positive pressure) supplied-air respirator. ( 1 ) Com bination supplied-air respirator, pressure-demand type, with auxiliary self-contained air supply. (2 ) Self-contained breathing ap paratus with full facepiece in positive pressure mode.# PREFACE
T he O ccupational Safety and H ealth A ct of 1970 em phasizes the need for standards to protect the health and safety of w orkers exposed to an ever-increasing num ber of potential hazards at their w orkplace. T he N ational Institute for O ccu pational Safety and H ealth has projected a form al system of research, with prior ities determ ined on the basis of specified indices, to provide relevant data from which valid criteria for effective standards can be derived. R ecom m ended stan dards for occupational exposure, which are the result of this work, are based on the health effects of exposure. T he Secretary of L ab o r will weigh these recom m endations along w ith other considerations such as feasibility and means of im plem entation in developing regulatory standards.
It is intended to present successive reports as research and epidemiologic studies are com pleted and sam pling and analytical m ethods are developed. C riteria and standards will be reviewed periodically to ensure continuing protection of the w orker.
I am pleased to acknowledge the contributions to this report on cadm ium by m em bers of my staff, by the Review C onsultants on Cadm ium , by the ad hoc com m ittees of the A m erican Industrial Hygiene A ssociation and of the Society of Toxicology, by R obert B. O 'C onnor, M .D ., N IO SH consultant in occupational m edicine, and by E dw in C. H yatt on w ork practices and respiratory protection. T he N IO SH recom m endations for standards are not necessarily a consensus of all the consultants and professional societies th at reviewed this criteria docum ent on cadm ium . Lists of the N IO SH Review Com m ittee m em bers and of the Review C onsultants appear on the following pages. " C ad m iu m " refers to elem en tal cadm ium and all cadm ium com pounds. A n " actio n lev el" is defined as h alf th e tim e-w eighted average co n ce n tra tio n e n v iro n m en tal lim it o f cadm ium . " O ccupational exposure to cad m iu m " is d efin ed as exposure to cadm ium a t a c o n c e n tra tio n g re a te r th a n th e a c tio n level. E xposures a t low er en v iro n m ental c o n c en tratio n s will n o t req u ire a d h e re n c e to the fol lowing sections, ex cep t fo r S ection 6 (b ) and 7 (d ). Sam ples shall be analyzed by th e m ethod provided in A ppendix II o r by a m eth o d show n to be at least equivalent in precision and sensitivity.

# Section 2 -Medical
M edical m onitoring shall be m ade available to all w orkers subject to occu p atio n al exposure to cadm ium .
(a ) P rep lac em e n t exam inations shall be m ade available to new o r reassigned em ployees p rio r to jo b placem en t, and, w ithin 6 m onths o f the prom ulgation o f a sta n d ard based on these reco m m endations, to em ployees already engaged in work involving exposure to cadm ium .
P rep lacem en t exam inations shall include com prehensive w ork an d m edical histories, a 14" X 17" P.A . ch est X -ray, m easurem ent o f forced vital capacity (F V C ) and forced expiratory volum e d u r ing th e first second (F E V j), m easurem ent o f blood pressure, blood analysis (b lo o d u re a nitrogen, com plete blood co u n t, and serum glutam ic oxalo ace tate transam inase o r o th e r liver enzym es), and urinalysis (m icroscopic exam ination, sugar determ in atio n , q u antitative p rotein determ ination, and specific gravity m easurem ent). A judgm ent o f th e w o rk e r's ability to w ork in positive o r negative pressure respirators shall be m ade.
T h e m ethod fo r p ro tein determ ination in urine shall be q u antitative and cap able o f detecting low m olecular w eight proteins (see A ppendix III). D eterm ination o f urine cadm ium levels is also recom m ended.
(b ) P eriodic exam inations shall also be m ade available. E xcept fo r urine p ro tein determ inations, w hich shall b e m ade available every 4 m onths, these exam inations shall be offered yearly, o r as otherw ise d irec ted by th e responsible physician.
T hese p eriodic exam inations shall include in terim w ork and m edical histories, urinalysis (w ith q u an titativ e p ro te in determ inations every 4 m o n th s), pulm onary function tests (FV C and F E V ,), an d blood pressu re. C h est radiographs shall be ta k e n if judged necessary by th e responsi ble physician.
In

# Section 4 -Personal Protective Equipment and Clothing
E ngineering co n tro ls shall be used if needed to m aintain airb o rn e cadm ium co n cen tratio n s a t or below th e lim its recom m ended in Section 1. C o m pliance w ith these w orkplace environm ental limits by th e use o f resp irators is p erm itted only during installation a n d testing o f engineering controls, during perfo rm an ce o f n o n ro u tin e m aintenance or rep a ir, during single op eratio n s, o r during em er gencies. W hen use o f a resp irato r is perm itted, it shall be selected a n d used in acco rd a n ce w ith the follow ing requirem ents:
(a ) F o r th e p u rpose o f determ ining the type o f re sp ira to r to be used, th e em ployer shall m ea sure th e c o n ce n tra tio n s o f cadm ium in th e w ork place initially and th e re a fter w henever control, process, o p eratio n , w orksite, o r clim ate changes o c c u r th a t are likely to increase the co n cen tratio n o f a irb o rn e cadm ium .

# ( b )
T h e em p lo y er shall en su re th a t no w orker is exposed to cadm ium in excess o f th e re c o m m en d ed lim its b ecau se o f im p ro p er resp irato r selectio n , fit, use, o r m ain ten an ce.
(c ) A resp irato ry p ro te c tio n p ro gram m eeting th e req u irem en ts o f 29 C F R 1910.134, w hich in c o rp o ra te s th e A m erican N atio n al S tan d ard P ra c tices fo r R espiratory P ro te c tio n , Z 8 8 .2-1969, shall be estab lish ed an d e n fo rc e d by th e em ployer.
( d ) T h e em p lo y er shall p ro v id e resp irato rs in ac c o rd a n ce w ith T ab le l -l , an d shall ensure th a t em ployees use th e resp irato rs p ro v id ed in a p ro p e r m an n er w h en w earing o f resp irato rs is required.
(e ) R esp irato rs selected from th ose described in T ab le 1-1 shall be th o se ap p ro v ed u n d er the provisions o f 30 C F R 11.
(f) T h e em ployer shall en su re th a t em ployees are p ro p erly in stru c te d in th e use o f resp irato rs as signed to th e ir use an d o n how to te st fo r leakage, p ro p e r fit, an d p ro p e r o p eratio n .
(g ) R esp irato rs specified in T ab le 1-1 fo r use in atm o sp h eres o f h ig h er c o n c e n tra tio n s o f a ir borne cadm ium m ay be used in atm o sp h eres o f low er cadm iu m co n cen tratio n s.
(h ) T h e em ployer shall estab lish and co n d u ct a p ro g ram o f cleaning, sanitizing, inspecting, m ain taining, repairing, an d sto rin g o f resp irato rs, to e n sure th a t em ployees a re p ro v id ed w ith clean resp irato rs th a t are in good o p eratin g condition.
(i) T h e em ployer shall periodically m onitor th e use o f resp irato rs to en su re th a t th e p ro p er type o f re sp ira to r is w o rn , to ev alu ate th e effec tiveness o f th e resp irato ry p ro te c tio n program , and to elim in ate any deficien cies in use and care o f respirators.

# Section 5 -Informing Employees of Hazards from Cadmium (a )
W o rk ers initially assigned o r reassigned to jo b s involving o cc u p a tio n a l expo su re to cadm ium shall be inform ed o f th e h azards, sym ptom s o f overex p o su re (in clu d in g in fo rm ation on the ch aracteristics o f o n se t a n d stages o f illness), ap pro p riate p ro c e d u re s to be ta k e n in th e ev ent o f an em ergen cy , and p re c a u tio n s to en sure safe use an d to m inim ize exposure. T h ey shall be advised o f th e availability o f relev an t in fo rm ation, includ ing th a t p rescrib ed in ( c ) below . T his inform ation shall be accessible to e a c h w o rk er occupationally exposed to cadm ium .

# (b )
A co ntinuing ed u catio n program , co n d u c te d by a perso n o r persons qualified by ex p erien c e o r special training, shall be instituted to en su re th a t all w ork ers have c u rre n t know ledge of jo b hazards, p ro p e r m aintenance proced u res and clean u p m ethods, an d th a t they know how to use resp irato rs correctly. It shall include a description o f the general n atu re o f the m edical surveillance p ro c ed u res and w hy it is advantageous to the w o rk er to undergo th e se exam inations.
(c ) R eq u ired inform ation shall be reco rd ed on a " M aterial Safety D ata S h e e t" as specified in A ppendix IV o r on any o th e r form approved for th e purpose by th e O ccu pational Safety and H ealth A dm inistration, US D e p artm en t o f Labor.

# Section 6 -Work Practices
( a ) E xhaust System s O p eratio n s creatin g w orkplace exposure to c a d m ium shall be enclosed to the m axim um extent p racticab le and be provided with local exhaust ventilation unless app ro p riate air sam pling and analysis have d em o n strated th a t con cen tratio n s are a t o r below th e environm ental limits. M ethods o th e r th an en closure and ventilation for m eeting exposure lim its to cadm ium m ay be used if they bring co n ce n tra tio n s in w orkplace air to or below th e environm ental limits. E ffluent air shall be clean ed to m e et any em ission stan d ard s th a t may becom e prom ulgated. A ir from th e exhaust ven tilatio n system shall n o t be recircu lated into the w orkplace.
E nclosures, exhaust hoods, an d ductw ork shall be k e p t in good re p air so th a t design airflows are m aintained. A irflow shall be m easured a t each h ood a t least sem iannually, and preferably m onthly. C o n tin u o u s airflow indicators are recom m ended, such as w a ter o r oil m anom eters properly m o u n ted a t th e ju n c tu re o f fum e hood and du ct th ro a t (m a rk ed to indicate a ccep tab le airflow ). A log show ing design airflow and results o f sem ian nual inspections shall be kept.
(b ) W elding, B razing, and T h erm al C utting W elding, brazing, o r therm al cuttin g o f m aterial containing cadm ium shall be p erform ed using local exhaust ventilation d em o n strated by air sam pling an d analysis to k eep cadm ium co ncentrations w ithin th e lim its o f Section 1. F o r single o p e ra tions w here local ex h au st ventilation is n o t availa ble, w here air sam pling has n o t b een perform ed,

# RESPIRATOR SELECTION GUIDE
- r w here air sam pling has d e m o n strated a likelihood o f o v erexposure to cadm ium fum e or dust, resp irato rs shall be provided and w orn as -specified in Section 4.
W here m olten cadm ium is u sed o r fo rm ed, te m p eratu res should be k e p t as low as possible c o n sistent w ith th e req u irem en ts o f th e o p eratio n to prev en t excessive fum e gen eratio n . A dditions of cadm ium should be m ad e in th e m an n er g e n e ra t ing th e least fum e. W h erev er possible, this should be accom plished by a u to m atic co n tro ls, with recording o f te m p e ra tu re and use o f alarm s o r in dicato rs fo r higher te m p eratu res.
(c ) E m ergency P ro ced u res E m ergency p ro c e d u re s shall be established for any ev en t w hich m ay resu lt in sub stan tial release o f airb o rn e cadm ium . Such p ro c e d u re s shall in clude provision for a p p ro p ria te resp irato rs as specified in S ection 4. Specific em ergency p ro c ed u res shall be designed fo r fires, to p ro te c t b o th in-plant w orkers and firefighters.
(d ) W ork C lothing W orkers shall w ear w ork clothing consisting of at least h a t, shirt o r blouse, pants o r skirt, and shoes. W ork clothing a n d stre e t clothing shall be exchanged at the beginning and th e end o f each w orkday, so th a t w ork clothing will n o t be w orn outside th e w orkplace. T h e em ployer shall provide for p ro p e r laundry o f clothing and shall instruct lau nderers on p ro ce d u re s to be ta k en to avoid in halation o f cadm ium -containing dusts.

# Section 7 -Sanitation Practices (a )
W here th ere is cadm ium -containing dust, cleaning should be p erform ed by vacuum pickup o r w et m opping. N o dry sw eeping o r blowing shall be p erm itted .
(b ) E m phasis shall be p laced upon p ro m p t cleanup o f spills, re p air o f eq u ip m en t and leaks, p ro p e r storage o f m aterials, and collection o f cadm ium -containing dust.
(c ) C adm ium -containing and cadm ium -plated m etal p arts should be k e p t sep a ra te from parts n o t containing cadm ium and m ark ed appropriately so th a t accid en tal exposures resulting from w elding and cuttin g will n o t occur.
(d ) Facilities shall b e m ain tain ed to p ro te c t foodstuffs an d food co n sum ption areas from co n tam ination by m aterials containing cadm ium . F ood storage, handling, and consum ption shall be sep a ra te from cadm ium w ork areas. Sm oking or carrying uncovered to b acco o r to b acco products in cadm ium w ork areas shall be prohibited.
(e ) A d eq u ate handw ashing and show er facili ties shall be provided. W orkers shall wash th eir hands before eating o r before using tob acco to p rev en t th eir absorbing additional am ounts o f c a d m ium com pounds.

# Section 8 -Monitoring and Recordkeeping
W orkers are n o t considered to be occupationally exposed to cadm ium if environm ental c o n ce n tra tions, as d eterm in ed on the basis o f an industrial hygiene survey to b e perform ed w ithin 90 days o f th e prom ulgation o f a standard, do n o t exceed the actio n level, ie, h alf the recom m ended TW A en vironm ental lim it, o r if there is no operation, storage, o r handling o f cadm ium in any form o r co n tam in atio n o f w orkplace air by cadm ium from o th e r sources. T h ese industrial hygiene surveys shall be re p e a te d at least every 3 years and w ithin 30 days after any p ro cess o r o p eratin g change like ly to resu lt in increases o f airb o rn e con cen tratio n s o f cadm ium . R eco rd s o f these surveys, including th e basis fo r conclu d in g th a t airb o rn e co n c e n tra tions o f cadm ium are a t o r below th e action level, shall be m ain tain ed until th e n ex t survey has been com pleted.
T h e follow ing req u irem en ts apply to o c c u p a tio n al exposure to cadm ium , ie, to w orkplaces w here th e actio n level is exceeded. E lectroplating is and has b een th e leading use fo r cadm ium , consum ing from 45 to 60% o f the am o u n t p ro d u ced ea ch year. A bout one m illion k ilogram s/year are used for stabilizers in plastics, and som ew hat less th a n a m illion kilogram s in pig m ents, w ith plastics a large con su m er o f the pig m e n ts. 12 O n e -q u arter to one-half m illion kilogram s o f cadm ium are used annually as an alloying agent in low m elting-point brazing alloys, in co p p er for autom obile rad iato rs, in silver-cadm ium electrical co n tacts, and in o th e r m etallurgical alloys. T hese 4 m ajor categories a c c o u n t fo r 80-90% o f the cadm i um used, with the rest d istributed am ong m inor uses such as nickel-cadm ium b atteries, fungicides, photography, and television picture tubes.
C adm ium dusts, fum es, and m ists are com m only p re sen t in som e sm elting processes involving zinc, co p p er, and lead as well as in specific processes fo r extracting cad m iu m . 13 NIO SH estim ates th a t 100,000 persons in the w ork fo rce are potentially exposed to cadm ium .  1941-1946. Bonnell34 cited S tephens, in 1920, and M ancioli, in 1940, w ho d escribed cases o f chronic illness due to occupational exposure to cadm ium . D uring W orld W ar II, the superim position o f nutritional d eficiencies o n to cadm ium exposure was suggested by N icaud and cow orkers38 as contributing to bone disease (o steo m alacia) in cadm ium w orkers in F rance. C adm ium is also believed to have been one causal fa c to r in the developm ent o f Itai-Itai ( " o u c h -o u c h " ) episodes in J a p a n . 1 (pp 137' l s , ) '39' 41

# Extent of Exposure

# Effects on Humans
T his section review s th e effects o f cadm ium on hum ans, m ostly from evidence developed in epidem iologic studies, in term s o f types o f effects such as organs o r o rgan systems affected. M any o f th ese studies to g eth er w ith additional ones are review ed, often in m ore detail, in th e section on Epidemiologic Studies. In the la tte r section, th ere is m ore em phasis on p o pulation studies and on a c o r relation o f hum an effects w ith airborne cadm ium co ncentrations.
(a )

# Pulm onary Effects (1 )
A cu te Effects A cu te intoxication from exposure to cadm ium oxide fum es in c o n cen tratio n s o f a t least several m illigram s/cubic m e te r has a characteristic clinical p ic tu re .42"45 Initially, th ere are virtually no sym p tom s; these usually ap p e ar 4-10 hours later, w hen dyspnea, cough, an d n o t infrequently a feeling o f co n striction in th e chest develop. O n occasion, w orkers m ay com plain o f substernal ch est pain o r a b urning sensation in th e ch e st th a t is a c c e n tu ated by coughing. Som e m ay also develop a flu like syndrom e c h a ra c teriz e d by shaky chills and m yalgia localized in th e b ack and limbs. U nder this la tte r circu m stan ce, th e illness m ay be m istaken fo r m etal-fum e fever. In any event, acu te pulm onary ed em a m ay develo p w ithin 24 hours. In such cases, physical ex am in atio n reveals an acutely ill p a tie n t w ith rales h e a rd on au scu ltatio n o f th e chest. C h est X -rays show b ilateral p u lm onary infil tra te s suggestive o f p u lm o n ary ed em a. Pulm onary function testing, w h en p erfo rm ed , has show n a d e creased fo rced vital cap acity (F V C ) and fo rced expiratory volum e durin g th e first seco nd (F E V ,). (b ) R enal Effects T h e m ost com m on abno rm ality fo u n d in w or kers exposed to cadm ium is p ro te in u ria .54,55,65 Friberg55 fo u n d p ro te in u ria in 81% o f 43 w orkers exposed to cadm ium fo r an av erage o f 2 0 years in th e alkaline storage battery industry and pointed o u t th a t the p ro tein ex creted w as n o t th e protein conventionally ex creted afte r kidney injury, ie, it w as o f low m olecular w eight, ab o u t 2 0 ,0 0 0 -30,000. Piscator*6 exam ined p ro te in in urines o f 79 cadm ium w orkers, 55 o f whom had been previ ously studied by F rib e rg .55 H e found an average ex cretio n o f p ro tein o f 50 m g/day in 10 healthy, unexposed subjects and 70-2,600 m g/day in cadm i um w orkers. In m en excreting m ore th an 150 m g/day, th e e lectro p h o retic p a tte rn o f urine p ro tein was ch arac teriz ed by a low album in co n te n t and increased co n ten ts o f a 2-, /3-, and yglobulins. In 75% o f th e m en excreting m ore th an 400 m g/day, th ere was a distinct /3 -globulin peak. In a few , he found a post-y-globulin fraction. C ad m ium w orkers also had a significantly higher c o n c e n tra tio n o f 7 -globulin and o f pro tein -b o u n d hexoses in serum th an did unexposed w orkers. P otts65 studied 70 battery w orkers and found pro tein u ria in 34% o f those exposed 10-19 years, and 82% o f w orkers exposed fo r over 30 years. Kazantzis and associates54 n o ted th a t d u ratio n o f exposure to cadm ium was im p o rtan t in th e developm ent of pro tein u ria. T hey fo u n d no p ro tein u ria in those ex posed fo r less th an 2 years; p ro tein u ria was found in 3 o f th e 4 exposed fo r 12 to 14 years and in all o f th o se exposed fo r 25 years o r m ore. The p ro te in u ria was ch aracterize d by excretion o f uri nary p ro tein o f low m olecular w eight, betw een 2 0 ,000 and 25,000. T he pathogenesis o f the p ro te in u ria has n o t been fully delineated, but V igliani67 has suggested th a t p ro tein m ay app ear in th e urine because tu b u lar-b o u n d cadm ium in te r feres w ith th e ability o f th e norm al kidney to catabolize im m unoglobulins and o th e r proteins. O th e rs 1 (pp l0f''106)-68,69 believe th a t it results from a d ecreased reab so rp tio n o f norm ally present protein by th e renal tubules. T his latte r view seem s m ore likely, ie, it is likely th a t low m olecular w eight p ro tein s appearing in the urine o f persons intox icated by cadm ium w ould have b een reabsorbed by th e norm al kidney, so th a t th e ir app earan ce in u rin e is an early sign o f renal dysfunction. How ev er, as F riberg and associates1 < D 112) have sug gested, b o th altered catabolism and altered re a b so rp tio n o f pro tein s m ay exist.
T h ere are few d a ta on acute renal effects. Bi lateral renal co rtical necrosis has been rep o rted in a fatal c a se . 44 T he co n c en tratio n o f cadm ium in th e kidney was given as *.7 ppm w et w eight, O lfactory E ffects A p o te n tia l con seq u en ce o f cadm ium exposure is dam age to the olfactory apparatus, w hich may result in to tal anosm ia. As with lung and kidney dam age, d u ratio n and co n ce n tra tio n of exposure a re probably im p o rta n t factors. P otts65 found ol factory dam age in 53-65% o f w orkers exposed 10-29 years and in 91% o f those exposed for m ore th an 30 years. T hirty-seven p e rc e n t o f the 43 w or kers studied by F riberg 55 show ed olfactory im pair m ent. A dam s and C ra b tre e 78 rep o rted cases o f hyposm ia and anosm ia am ong w orkers exposed to cadm ium oxide dust as well as to nickel dust, in an alkaline-battery o p eration. A group o f 106 battery w orkers w ere co m p ared with 84 age-m atched co n trols. O lfactory acuity was ju d g ed from each sub je c t's evaluation o f his ow n acuity and from a ph enol sm elling test. B attery w orkers rep o rted sig nificantly m ore anosm ia (15% vs 0% ) and did less well on th e phenol sm elling te st (27% vs 5% ). T h ere was a positive correlation betw een p ro tein u ria and anosm ia; 17 w orkers w ith p roteinuria also w ere anosm ic. E xam ination o f noses showed m any cases o f local irritation from dust, som e subm u cosal fibrosis in m ild cases of deficient olfactory acuity, and cases o f ulceration, occasionally with dry crusting, in m ore advanced cases. Biopsy m aterial from one case show ed a m ild nonspecific subm ucosal chronic inflam m ation w ith a few small loose focal accum ulations o f lym phocytes and a few widely sc attere d eosinophils. T he authors a t trib u te d th e anosm ia to exposure to eith er cadm i um o r nickel, o r to a m ixture o f the two. T he p o p ulation studied by Friberg55 was also exposed to nickel. P otts65 did n o t re p o rt nickel exposures, b u t th e w orkers m ad e b atteries, so there w ere un doubtedly exposures to nickel dust, as well as to cadm ium . H ow ever, Tsuji e t al79 reported th a t several w orkers exposed to cadm ium in a zinc refinery, w ithout evidence o f exposure to nickel, had a so-called insensitiveness to smells.
(d ) H em atopoietic System A cute effects on the blood a fte r respiratory ex posure at a high co n c en tratio n o f cadm ium have been no ted both in hum ans and in anim als.44,80 E levated hem oglobin in som e hum an subjects may well have been th e result o f h em o concentration from pulm onary e d e m a . 44
A nem ia has been described in w orkers exposed fo r a long tim e to cadm ium oxide dust and fu m e .38,55,81 T he anem ia was usually m oderate. In a g ro u p o f w orkers exposed to cadm ium 5-30 years, Piscator, in u n published studies review ed by F riberg, P iscato r, T h e Itai-Itai (" o u c h -o u c h " ) disease w hich o c cu rred in certain areas o f Ja p a n was attributed to pollution o f w ater an d crops by industrial, cadm i um -containing w aste. 1 40'41.89 The disease is apparently o steom alacia and involves painful jo in ts and bones, especially in th e back and legs. T hose affected w ere m ostly m ultiparous, post m enopausal w om en. A nutritionally deficient (low calcium and p ro te in ) d iet was perhaps an addi tional facto r. Low estrogen levels may also have had som e bearing on th e osteoporosis seen in these cases.
(2 ) T eeth T h e d evelopm ent o f a yellow ring a t the neck o f th e to o th was re p o rte d in early epidem iologic sur veys in occupationally exposed persons and was at one tim e suggested to be a w arning sign o f chronic cadm ium in to x icatio n .62,90 W h eth er this is because o f surface ab so rp tio n o f cadm ium , reaction with In an epidem iologic study o f c an c er in persons exposed to cadm ium , K olonel101 co m pared the in cidences o f several types o f c a n c e r in persons hav ing an in ferred o ccu p atio n al history o f cadm ium w ork w ith those in a co n tro l population. The basis fo r inferring a history o f o ccu p ational exposure to cadm ium was ind irect, from jo b classification in fo rm atio n revealed in an interview on adm ission to a c a n c e r research hospital. T h e te st and control p opulations w ere all w hite m ales, aged 50-79 years, and w ere all referred to th e Roswell Park M em orial H ospital in Buffalo, N ew Y ork, because o f suspected neoplastic disease. O ne group of c o n trols w ere those found to have nonneoplastic gas troin testin al disease; a second group o f controls w ere those found to have colon cancer. Kolonel found a significant increase in ren al can cer, and a nonsignificant increase in p an creatic ca n ce r am ong th e p atien ts th o u g h t to have been exposed to ca d m ium . H e an ticip ated an increased incidence of p ro static can cer, b u t found none. H e looked for a sim ilar increase in c a n c e r am ong those exposed to cadm ium from dietary intake o f cadm ium o r from sm oking, b u t the association was questionable. In view o f th e deficiencies in his d a ta on o ccu p a tional histories, conclusions from this study are u n certain.
In a later publication based on these data, K olonel102 co m m en ted on evidence o f a synergistic relationship betw een exposure to cadm ium and cig arette sm oking. In th e b elief th a t th e greater th a n additive effect could n o t be acco u n ted fo r by the in creased cadm ium exposure, he suggested th a t som e o th e r co m p o n en t o f cigarette sm oke C adm ium has also caused food poisoning from the use o f a cadm ium -plated refrig erato r sh elf as a grill to hold steak over c h a r coal for broiling.109 A 2-year old child with en cep h alopathy originally attrib u ted to lead was found to have a very high cadm ium concentration o f 710 (j.g/liter in his urine. It was found th a t the child was fond o f licking freshly polished w hite shoes (polish solution containing 275 pig C d/100 m l), occasionally a te silver polish (185 /xg/100 m l), and ate red p ain t (5 0 0 m g /100 g) from his c rib . 110 Bui e t al111 analyzed the chrom osom es in lym phocytes from Swedish battery-factory w orkers and Itai-Itai p atien ts from Jap a n , to gether with co n tro ls from Sw eden and Jap an , and found no significant differences in chrom osom al aberrations betw een cadm ium -exposed people and their respective controls. H ow ever, sizes o f populations studied w ere small in each case. M ean frequencies of ab erratio n s ranged from 2.0% in Swedish b a t tery w orkers to 6.7% in Itai-Itai patients. Shiraishi and co w orkers112'113 cu ltured cadm ium sulfide with h um an leukocyte cells and exam ined leukocyte chrom osom es from 7 Itai-Itai patients, and in each case found an increased incidence o f chrom osom al aberratio n s over controls. T he rate o f abnorm ali ties in th e Itai-Itai p atien ts112 ranged from 14 to 64% o f th e 50 cells exam ined, m uch higher than th e rate found by Bui e t a l. Bonnell34 exam ined 100 w orkers exposed to ca d m ium oxide fum es and 104 controls with sim ilar age distribution in 2 B ritish copper-cadm ium alloy facto ries. N in eteen o f th e 100 exposed w orkers h ad em physem a, p ro te in u ria , o r both, while 3 o f th e co n tro l group had e ith e r em physem a or p ro tein u ria. All 19 m en w ith signs and sym ptom s had been exposed to cadm ium for m ore th an 5 y ears and 13 o f them fo r m ore th a n 15 years. Four additional w orkers required hospitalization because o f shortness o f b reath. Significant dif feren ces in results from certain respiratory fu n c tion tests w ere found by K azantzis126 betw een the exposed and th e co n tro l groups in these sam e fac tories, particularly in th e tim e co n sta n t o f the ex p iratory forced vital capacity curve. In the group o f these w orkers exposed to cadm ium for m ore th an 10 years, B uxton 127 found th a t the volum e of residual air and th e residual q u o tie n t (ie, residual air as expressed as a p ercentage o f th e total lung volum e) w ere both significantly increased. This finding is consistent w ith F rib e rg 's . A hlm ark and associates76 rep o rted on 110 cadm ium -exposed w orkers and 22 controls. Several te st m easurem ents show ed th a t kidney functions w ere red u ced w ith long exposure. U rinary protein ex cretion increased regularly w ith length o f expo sure from 100 m g/24 hours (ranging from 50 to 170) at less th an 5 years to 955 (ranging from 370 to 1800) m g/24 ho u rs a t 31 years and over. T he incidence o f kidney stones increased from 9.1% in the controls to 12.3% in the 6 -to 10-year exposed group and to 43.6% in the g rea ter th an 15-year ex In th e age g ro u p 50-59, th ere was a statisti cally insignificant in crease in hyperten sion in ex posed w om en. T h e re w as a significant increase in average h aptoglobin an d sed im en tatio n ra te in the 40-49 age group and a nonsignificant increase in the 18-29 y ear age group. Serum iron was low er in th e 50-59 year group. T here w ere n o significant differences in urinary findings. A m ong the controls th e re was one case w ith a very high excretion of /32-m icroglobulin; th e p a tte rn obtained by elec tro p horesis o f urine suggested an effect on tu b u lar fu n ctio n b u t th e re was no glucose in the urine, and a b acterial infection involving th e tubules was sug gested as th e explanation. T here was a slight tu b u lar dysfunction in a 71-year-old exposed w om an, b u t w ithout in creased /32-m icroglobulin excretion. She had b een classified as a suspect case in 1969.
P iscato r e t' a l131 also observed significant dif feren ces in blood and urine cadm ium , and found th a t u rin e cadm ium , b u t n o t blood cadm ium , in creased w ith age. T hey also n o ted a slight decrease in u rine zinc w ith exposure tim e, ex cept th a t urine zinc was increased by use o f drugs for trea tm en t of hypertension. S m okers had significantly higher blood cadm ium levels th an nonsm okers; dif feren ces betw een cadm ium -exposed sm okers and n onsm okers w ere n o t found in urinary excretion o f cadm ium b u t c o n tro l sm okers ex creted m ore cad m ium th an co n tro l nonsm okers. It was believed th a t cadm ium m ight have b een deposited on cig arettes during w ork, th en vaporized during sm oking and inhaled. T hey found a significant co r relation betw een blood and urine cadm ium in nonsm okers exposed less th a n 1 0 years but n o t in sm okers.
K jellstrom and asso ciates132 studied the ex cre tion o f /3 2-m icroglobulin in m ale and fem ale w or kers in th e battery factory originally studied by F rib e rg .55 T h ere w ere 240 m ale and fem ale w or kers exposed to cadm ium oxide dust and to nickel hydroxide dust in th e study group, and there were 87 unexposed m ale controls. T he exposed w orkers w ere em ployed in th e d ep a rtm e n t w here m aterials fo r b attery electro d es w ere m ade (m aterial plant) o r w here th e electro d es and batteries w ere assem bled (assem bly p lan t). S tationary and personal sam ples w ere co llected on m illipore filters except in 1959 and p rio r years and analyzed by atom ic ab so rp tio n sp ectrophotom etry. P article size analy sis in 1972 show ed th a t 95% o f the particles w ere sm aller th an 5 /xm. E nvironm ental concentrations had been occasionally m easured in the factory from 1946 on, b u t system atic m easurem ents based on personal sam pling had n o t been perform ed. In dividual sam ples in the assem bly plant in 1946, based on stationary sam plers, averaged 6 . T he w orkers w ere draw n from 3 different fac to ries, an electro n ic w orkshop, a nickel-cadm ium storage battery factory, and a p la n t producing c a d m ium . E ach factory h a d a co ntrol group selected to m atch th e exposed group in sex, age, w eight, height, sm oking habits, and socioeconom ic status. Since no im p o rtan t m odifications had o ccu rred in th e different industrial processes since th eir institu tion, th e au thors believed th a t levels o f airborne cadm ium found in the 3 plants w ere quite rep resen tativ e o f p ast exposure. A description o f th e exposed groups and the w orkroom cadm ium levels found are given in T able III-1.
C o n tro l groups w ere described as Cl, C 2, and C 3, co rresponding to the th re e exposed groups. E xposed groups w ere exposed to dust of cadm ium o r its com pounds; fo u r w orkers in G roup E3 w ere also interm ittently exposed to fum e.
In group E l , th e only change was a slight in crease in urine cadm ium ; th ere w ere no significant differences in pulm onary function indices, b u t it was n o ted th a t an effect o f cigarette sm oking on pulm onary function was evident.
In group E 2, in b o th sm okers and nonsm okers, all pulm onary indices w ere on the average low er th a n th e corresponding co ntrol group, b u t these differences w ere n o t statistically significant. Blood and urine cadm ium con cen tratio n s were higher th a n co n tro l levels. E lectrophoresis show ed evidence o f glom erular proteins in four w orkers. O ne w orker know n to have glom erulonephritis had w hat was described as excessive proteinuria.
In group E3, pulm onary indices (FV C , F E V l and peak expiratory flow ra te ) w ere significantly low ered. C ough b u t n o t ex p ectoration was m ore com m on in E3 th a n in C3 w orkers. T here w ere slight b u t statistically significant changes in som e o f th e blood enzym es, viz, an increased /3 -galactosidase, an increased lactic dehydrogenase, and a decreased RBC acetylcholinesterase; h em atocrit was also low er in E3 th an C3. H ow ever, these changes w ere n o t sufficient to suggest adverse health effects. F u rth e r details o f these stu d ies133,134 as well as o f those on o th e r w orkers exposed to cadm ium have been published in a com prehensive rep o rt, also from th e C atholic U niversity o f Louvain, Belgium, by M atern e et a l. 135 Som e o f these w orker groups w ere also exposed to lead, w hich may m ake som e o f th e observations less clearly attrib u tab le to cad m ium . H ow ever, th e au th o rs co n cluded th at lead ab so rp tio n had little o r no role in the kidney changes, an d th a t th e effects in the kidneys w ere from cadm ium ab so rption by these w orkers. In F acto ry I, involving electronic m an u facture, 26 ex posed w om en and 26 control w om en w ere studied.
T h e re w as no lead exposure in this group. In F ac tory II, w here nickel-cadm ium batteries w ere m ade, 2 1 exposed m ale and 6 exposed fem ale w or kers w ere studied, w ith 19 co n tro l m ales and 4 c o n tro l fem ales. In F actory III, involving cadm ium p ro d u ctio n , 25 exposed and 25 co ntrol m ales were studied. In F actory IV, also involving cadm ium p ro d u ctio n , 6 6 exposed and 65 control m en w ere studied. C ontrols w ere m atched with cadm ium -ex posed w orkers in age and in sm oking habits. A ir bo rn e cadm ium c o n c en tratio n s w ere variable, ranging betw een 7 and 19 /xg/cu m in F actory I, 6 -94 in F actory II, 1.2-97 in F actory III, and up to several m g/cu m in F actory IV, after om itting several values (eg, 27 m g/cu m ) th a t w ere believed du e to gross con tam in atio n o f sam ples. The co n ce n tratio n ranges m entioned w ere sm aller in specific w ork sites w ithin a factory. D ifferences betw een exposed and control groups w ere often less rem arkable th an differences betw een sm okers an d nonsm okers. In F actories II and III th ere w ere decreases in hem atocrit; while this m ight be attrib u te d to lead, airborne lead c o n ce n tra tio n s w ere in th e range o f 40-50 tg/cu m, w hich seem s unlikely to be high enough to cause anem ia, so possibly the reduction in hem atocrit w as due to cadm ium alone o r to cadm ium and lead.
A n o th er group consisting o f 108 exposed and 110 co n tro l w orkers w ere exposed a t 74-210 yxg/cu m total (2 0 -3 0 /xg/cu m respirable) cadm i um dust, o f whom 18 exposed w orkers had w hat w as d escribed as pathologic urine proteins on elec trophoresis. P ro tein u ria was also seen in som e w orkers in F acto ries III and IV, to g eth e r with p u l m onary function decreases. T he au th o rs concluded th a t, in o rd e r to p rev en t any renal im pairm ent, air b o rne cadm ium , w h eth e r dust o r fum e, should not exceed 50 ig/cu m.

# Animal Toxicity
In th e ensuing discussion o f anim al toxicity, em phasis is given to th o se investigations w hich sig nificantly a d d to in fo rm atio n from hum an studies, eg, rep ro d u ctiv e effects an d ex p erim ental c a r cinogenesis, w ith a re su lta n t lack o f em phasis on those effects m ore extensively stu d ied in hum ans, such as ren al and p u lm o n ary effects. In addition, in such are a s as te stic u la r effects and biochem ical studies, w here th e re are m any p u b lished studies, the m ore rep resen tativ e o r im p o rta n t studies have been selected fo r discussion. D alham n and F rib erg143 adm inistered cadm ium sulfate sc to 3 groups o f rabbits, 6 /group, 6 days/w eek, for 10 w eeks, at 650 /xg C d/kg. Tw o of th e groups w ere in jected th rice daily with dim ercap ro l, one a t 4 an d th e o th er a t 12 m g/injection; th e th ird group received only cadm ium sulfate. F o u r o f th e anim als on the high dose o f dim ercaprol and 3 receiving only cadm ium sulfate died during the experim ent. T h ere was a progressive w eight loss in all groups, greatest in high-dose dim ercap ro l anim als. P ro tein u ria developed in all b u t tw o rabbits, ea rlie r in m ost of the anim als receiving th e higher dose o f dim ercaprol. T here was a significant and progressive decrease in hem oglobin co n c en tratio n s in th e blood, b u t a sig nificant decrease in ery th ro cy te count o ccurred only in the high dose dim ercaprol animals. P ost m o rtem exam ination show ed th a t all anim als had h e p atic cirrhosis, nephrosis, and splenic fibrosis. O th e rs146-151 have also found hypertensive effects o f C d (II) in anim als.
P o rte r e t al152 found no elevation o f blood p res sure in C d(II) intoxication. T hey adm inistered c ad m ium ac etate ip a t 2 mg C d/kg to fem ale Sprague-D aw ley-derived rats, th en a second ip dose o f 1 mg C d/kg 3 w eeks later. From days 14 to 27 after th e seco n d adm inistration, various autonom ic drugs w ere adm inistered in sequence by vein, and systolic blood pressures w ere recorded. W ith norep in ep h rin e b u t n o t epinephrine, drugs causing elevated blood pressure in co n tro l rats, th ere was a lesser elevation in cadm ium -treated rats, with acetylcholine, isoproterenol, and atropine, b u t not pro p ranolol, drugs causing d ecreased blood pres sure in co ntrol rats, th ere was a lesser decrease in cad m iu m -treated rats. A ortic strips from cadm iumtre a te d rats had a dim inished reactivity to an giotensin, ep in ep h rin e, barium , and tyram ine. T he au th o rs co n cluded th a t cadm ium desensitizes rat vasculature to vasoconstrictors and dilators inde p en dently o f any ability to cause hypertension. found in all 80 anim als. Sim ilar d ata were developed by M ason e t al*55 a t various doses of cadm ium chloride (0.57-6.8 mg C d/kg) given sc to rats. A gain, edem a p reced ed an ischem ic necrosis w hich was associated w ith increased intratesticular pressure, hem orrhaging, and ultim ate interference w ith testicu lar blood supply. In this study, a doseresponse relation w as found a t th e low er dose levels, 0.57-1.4 m g/kg. A t the low est dose, no ef fe ct was observed, a t 0.85 m g/kg ischem ic necrosis o f sem iniferous tu b u les o c c u rre d in 32% o f the rats, a t 1.1 m g/kg th e re was a 90% incidence, and at 1.4 m g/kg 100% o f th e rats h a d these injuries. It was suggested th a t the unusual sensitivity o f the testes to cadm ium w as related to the unique vascu la tu re , ie, pulseless, sem istagnant flow, w hich m ight have facilitated alteratio n o f capillary e n dothelial perm eability by cadm ium .
Sangalang and O 'H alloran 156 studied testicular injury and changes in androgen synthesis in brook tro u t exposed to C d (II) fo r 24 h o u rs at 1 ,2 , o r 25 ppm . T estes o f the fish tre a te d a t 25 ppm show ed extensive h em orrhagic dam age. Form ation o f 11k e to testo ste ro n e, 11-/3-hydroxy testosteron e, and testo stero n e from 14C -pregnenolone in vitro was used to study the effects o f C d (II) exposure on an drogen synthesis by th e testes. T h e results show ed th a t cadm ium inhibited th e form ation o f the ste roids in vitro; w h e th er this reflects the situation in vivo is n o t know n. H ow ever, the study suggests th a t cadm ium -induced testicu lar dam age is not confined to species w ith scrotal testes.
In o rd e r to investigate the testicular dam age from cadm ium in m o re detail, Parizek91 injected rats and m ice w ith cadm ium chloride (2.2-4. Parizek e t al170 fo u n d th a t in jectio n o f cadm ium a c e ta te in th e range o f 30-40 ptm ole/kg in several groups o f p reg n an t rats cau sed 40% o f the p reg n an t rats to die w ithin th e first 24 hours after cadm ium adm inistratio n . T h e rats w ere injected on th e 2 1 st day o f p regnancy. In 80% o f these p reg n an t rats, b ilateral h em o rrh ag ic ren al necrosis was observed. M etallothionein w as first isolated by M argoshes and V allee194 from horse kidney cortex and was show n to co ntain a high co n c en tratio n o f cadm ium w ith a lesser am o u n t o f zinc. Subsequently, Kagi and V allee195,196 purified this m aterial, showing th a t it was a hom ogeneous, low m olecular w eight p ro te in (1 0 ,0 0 0 m ol w t) containing 5.9% cadm i um , 2.2% zinc, and 8.5% sulfur, and having very low spectral absorptivity at 280 nm , indicating a lack o f arom atic am ino acids in its com position b u t w ith a specific absorptivity a t 250 nm due to cadm ium -sulfur groupings. T hese investigators sug gested th a t th e m etal-free p ro tein be called thionein, and th a t th e cadm ium protein be called cadm ium -thionein. N inety-five p e rc e n t of all sulfur in th e m etal-free th ionein m olecule was presen t as th e sulfhydryl group o f cysteine. M oreover, cysteine a cc o u n ted for 1 o f every 3 to 4 am ino acids, ie, 25-30% o f the am ino acids o f this p rotein are cysteine m olecules. Pulido e t al 197 show ed th a t a sim ilar p ro tein co u ld be isolated from hum an ren al cortex. T his purified m etallothionein had a m o lecu lar w eight o f 10,500 and contained 4.2% cadm ium , 2.6% zinc, 0.5% m ercury, and 0.3% co p p er. As with th e equine pro tein , th e sulfur c o n te n t w as high, nam ely 8 . 1 %, and th e characteristic ultraviolet ab so rption ban d a t 250 nm was present.
Follow ing these early reports from the H arvard g ro u p , 194 197 one gro u p o f w orkers a t the K arolinska Institute in Sw eden198 and an o th er a t Dalhousie U niversity in N ova S cotia199'

# Correlation of Exposure and Effect
C adm ium com pounds affect m any organs and body system s. T h e re is evidence from m an or low er anim als o f effects on the respiratory trac t, on th e nervous system , on th e liver, on form ed ele m ents o f th e blood, on vascular function, on m ale a n d fem ale gonads, on thyroids, o n p an creata, on bones, and, probably m ost im portantly, on kidney function. In addition, th ere is evidence th a t cadm i um m ay cause c a n c e r and birth deform ities. W ith increasing exposure m ore cadm ium th an can be bou n d by m etallothionein will even tually be accu m u lated in th e kidneys. C adm ium will th e n exchange w ith zinc in enzym es necessary fo r reab so rp tio n and catabolism o f proteins. . . As a result o f th ese anti-enzym atic actions less p ro te in will b e catabolized o r reab so rb ed , causing tu b u la r p ro tein u ria. C adm ium excretion will in crease also as less m etallothionein will be re ab sorbed. A t this stage the accum ulation rate o f c ad m ium will becom e slow er, b u t cadm ium will still be re ab so rb ed and cadm ium levels in the tissue m ay get still higher. T he reabsorption defect will be g reate r and eventually renal cadm ium will cease to increase. T u b u lar cells will be dam aged by cadm ium , and it is conceivable th a t cadm ium will be ex creted to g e th e r with desquam ated tu b u lar cells, resulting in a decrease in renal levels o f cadm ium . If glom erular function is im paired, there will also be less filtration o f m etallo th io n ein ."
It is ap p are n t th a t urinary excretion o f low m o lecu lar w eight p ro tein s and perh ap s also urinary ex cretion o f glucose o r am ino acids constitute early evidence o f altered tu b u lar function. This evidence does n o t usually a p p e ar until som e tim e after exposure at sufficiently high cadm ium co n cen tratio n s has started . T suchiya64 found no p ro tein u ria in m en exposed a t an average o f 125 /xg/cu m for less th a n 9 m onths, and w orkers with m ore th an 5 y ea rs' experience had the highest urine p ro tein levels. Kazantzis e t al54 noted th at d u ra tio n o f exposure was im p o rtan t in the d ev elopm ent o f p ro teinuria; th e re w ere no w orkers w ith p ro tein u ria in th e group with less th an 2 y e ars' exposure, th e re w ere 3 w orkers with p ro tein u ria in th e group o f 4 exposed 12-14 years, and all w orkers exposed m ore th a n 25 years had p ro tein u ria. H ow ever, w ith th e rep lacem en t o f m ale w orkers w ith w om en, co n tro l m easures to im prove w or k room hygiene have also been instituted. Thus, the app aren tly g reate r resistance o f w om en to cadm i um , evidenced by few er effects in w om en th an in m en previously em ployed in th e sam e w orkplace, is probably due to the low er con cen tratio n s of cadm ium aerosols to w hich w om en w ere exposed. F o r exam ple, P iscator e t al131 studied w om en w or kers, m ost o f w hom w orked in the plan t previously p o p u lated by th e m en studied by Friberg,55 and fo u n d significantly few er effects th an in the m en studied previously; in fact, it is doubtful th a t his pop u latio n was adversely affected a t all. H ow ever, co n cen tratio n s to w hich the w om en w ere exposed w ere significantly less (u n d e r 100 yu.g/cu m ) than those o f th e m ale w orkers (3-15 m g/cu m ), w ho developed m any toxic effects, including em physem a and renal dysfunction. T svetkova95 studied fem ale w orkers in a p lan t w here co n ce n tratio n s o f cadm ium w ere reportedly 0.1-25 m g/cu m; she found no effects in th e w orkers (although she observed rick ets and d en tal troubles in off spring), b u t it is n o t evident th a t she investigated such effects as those on th e pulm onary and renal ap p aratu s. L auw erys e t a l133 found no adverse ef fects in fem ale w orkers b u t did observe evidence o f a ltered pulm onary and renal function in m ale w orkers. H ow ever, the fem ale w orkers w ere ex posed a t 31 /xg/cu m w hereas m ale w orkers w ere exposed at higher co n ce n tra tio n s (66 p-g/cu m and higher).
Tsuji e t al79 did n o t p re sen t environm ental expo sure d ata, so it is n o t clear w h eth er th e ir m ale and fem ale w orkers w ere exposed at th e sam e co n ce n tratio n s. If they w ere, a conclusion th a t the m ale and fem ale w orkers did n o t differ significantly in sensitivity w ould be w arranted. T h e re was a 14.7% in cidence o f p ro tein u ria in th eir m ale w orkers and 15.5% in fem ale w orkers; th e re was a 7.8% in cid ence o f glucosuria in m ale w orkers and a 1.4% incidence in w om en, based on m easurem ent by te st ta p e, w hich m ay be an inadequately sensitive m ethod.
(n ) Q u an titativ e R elationships     P riority should be given to m ortality studies of cadm ium w orkers w ithout co n co m itan t exposure to o th e r toxic m aterials and to long-term anim al studies at doses up to m axim ally to lera te d ones.

# SUM M ARY OF CANCER M ORTALITY D A T A OF KIPLING A N D W ATERHOUSE9 A N D OF LEM EN ET A L07
In view o f the p resen t u n certain ties in the evidence on teratogenicity and carcinogenicity of cadm ium in o ccu p atio n al exposure, a standard b ased on th ese effects is n o t now recom m ended. This reco m m en d atio n should be reconsidered if additional d a ta on these points th a t w arrant such reco n sid eratio n are developed.
T h e reco m m en d ed lim its o f 40 /xg/cu m (T W A ) and 200 pig/cu m (ceiling) are fo r to tal particulate cadm ium . Thus, lim its based only on small, socalled respirable, p articles, are n o t recom m ended. C adm ium oxide and m any o th er form s o f cadm ium are n o t in ert, varying in th eir solubilities in w ater and probably in body fluids, so th a t large particles n o t reaching th e alveoli may still be toxicologically active because th ey can be rem oved from the u p p er respiratory tra c t by ciliary action and tra n s ferred to the gastrointestinal trac t. Thus, som e of th ese large particles w ould probably be swallowed and beco m e system ically toxic th ro u g h gastroin testinal absorption (th o u g h gastrointestinal absorp tio n w ould b e e x p ected to be less th an absorption from the respiratory tra c t).
It has b een im plicit in the environm ental limits, such as T L V 's th a t have prevailed fo r m any years (see discussion o f previous stan d ard s in the section ab o v e ), th a t cadm ium oxide fum e is m ore toxic th a n cadm ium oxide dust. It seem s probable th a t th e basis fo r this is th e assum ption th a t fum es, being usually o f sm aller p article sizes th an dusts, will p e n e trate m ore efficiently into th e lungs and th u s be m ore efficiently absorbed by th e blood. It is proposed th a t m andatory m edical surveil lance include p rep lace m en t and periodic exam ina tio n s o f lungs, kidneys, and blood pressure. In ad dition, blood co u n ts, studies o f liver function, and, in m ale w orkers, palpation o f the prostate are recom m ended. Pulm onary fu n ctio n tests should be p erfo rm ed periodically, and ch est X-rays should be tak e n if indicated from results o f periodic ex am inations. F or com parison, prep lacem en t ex am inations and exam inations at term ination o f em ploym ent involving cadm ium exposure should in clude X -rays as well as pulm onary function tests. Q u antitative analysis o f urine p ro tein should be c o n d u cted frequently, since this should give early and probably the first indication o f adverse effects o f cadm ium . P ro tein u ria w ith its im plications o f renal dysfunction is less likely to be reversible as it continues, so early d etectio n o f low m olecular w eight proteins in th e urine, w ith the expected result o f steps to im prove hygiene and w ork p ra c tices, should p rev en t serious an d irreversible ef fects o f cadm ium . T herefo re, it is proposed th at analysis o f urine be cond u cted every 4 m onths as well as before p lacem en t an d a t term ination. P ro ced u res for estim ations o f proteins in urine are d escribed in A ppendix III; the conventional boiling te st is n o t ad e q u a te for cadm ium -induced proteinuria. If a w o rk er is found to begin to ex crete significant am ounts o f p rotein in his urine during exposure to cadm ium , electro p h o retic ex am ination o f th e urine fo r the p resence o f various proteins, especially for peaks in the /3-globulin re gion, will b e helpful in deciding w hether exposure to cadm ium is involved in th e genesis o f the proteinuria. A lternatively, specific analysis for /32m icroglobulin can be perform ed. It can be p e r form ed by radioim m unoassay o r radial im m unodif fusion, w hich give com parable results275; sem i-auto m atic p ro ced u res allowing sim ultaneous processing o f 24 sam ples have been described. (f) W ork P ractices W o rk practices are discussed in C h ap ter VI. B razing w ith alloys containing cadm ium (o ften re fe rred to as silver soldering) is especially h azardous b ecause o f the high concen tratio n o f cadm ium oxide fum e pro d u ced , so good local ven tilation and, o ften , respiratory p ro tection are n eeded. Storage, handling, and eating o f food in cadm ium exposure areas should be prohibited to p rev en t food con tam in atio n an d subsequent in gestion o f cadm ium . W hile cadm ium does n o t pose a fire hazard, its deposition on sm oking m aterials m ay result in g en eratio n and inhalation of cadm i um oxide fum e a t a later tim e, so th a t sm oking as well as the carrying o f u n covered sm oking m ateri als in th e w orkplace should be prohibited. T here isn 't good evidence th a t cadm ium aerosols will p e n e tra te the skin, b u t th e ir deposition on clothes m ay result in aerosol g en eration (eg, blow ing of d u st) away from w ork, w hich m ay increase the w o rk ers' exposure as well as cause his family to be exposed. F or this reason, it is pro p o sed th a t w or kers be req u ired to change w ork clothing before leaving w ork. U nder these conditions it should n o t be necessary to com ply w ith m any o f the provisions o f this recom m ended stan d ard , w hich has been p rep a re d prim arily to p ro te c t w o rk ers' health under m ore hazardous circum stances. C o ncern for w o rk ers' health requires th a t p ro tectiv e m easures be instituted below the en fo rceab le limit to ensure th a t exposures stay below th a t lim it. F or these reasons, an action level o f cadm ium has been defined as o ccu p atio n al exposure above half the recom m ended TW A environm ental limit, thereby delineating those w ork situations w hich do not require the expenditure o f health resources for e n vironm ental and m edical m onitoring and as sociated recordkeeping. T his level has been chosen on the basis o f professional ju d g m e n t ra th e r than on q u antitative d ata th a t d elineate nonhazardous areas from areas in w hich a hazard may exist. H ow ever, brazing, w elding, o r th erm al cutting with cadm ium alloys presents a significant hazard re gardless o f the T W A c o n cen tratio n , and such operations should be perform ed only in a c co rd an ce with the recom m ended standard. Sim ilarly, food storage, handling, and eating should be pro h ib ited in cadm ium w ork areas re gardless o f TW A co n cen trations. Silver Brazing Silver brazing, com m only called silver soldering, is the process o f joining m etals by heat with a silver alloy filler m etal. M any filler m etal alloys co n tain cadm ium , w hich can pro d u ce cadm ium oxide aerosol w hen o verheated, so care m ust be taken to control the tem p e ra tu re of silver brazing o p eratio n s if the alloy contains cadm ium . U nder no circum stances should a to rch flam e be applied directly to such an alloy. T he h eat o f the base m etal should be used to m elt the filler m etal and cause it to flow. Silver brazing w ith cadm ium -containing alloys should be perform ed only with satisfactory local exhaust or with appropriate respiratory p rotection.

# V I. W O RK PR A C TIC ES
(c ) W elding, C utting, and H eating W elding and therm al cutting o f m aterial co n taining cadm ium m ust be perform ed only with local exhaust ventilation dem o n strated by sam pling and analysis o f breathing zone atm ospheres to be sufficient to m aintain airborne cadm ium at or below recom m ended limits. For single operations, w here local exhaust ventilation is not available or w here air sam pling and analysis has not dem o n strated accep tab le air co n cen trations, suitable resp irators (listed in C h ap ter I) m ust be provided and worn.
W here m olten cadm ium is used o r form ed, tem p eratu res should be k e p t as low as possible c o n sistent with th e re q u irem en ts o f th e w ork o p e ra tion to p rev en t g en eratio n o f excess fum e. W h er ever possible, this should be accom plished by au tom atic co n tro ls, with reco rd in g o f tem p eratu res and use o f alarm s o r o th e r in d icato rs o f excessive tem p eratu res. If possible, avoid using cadm iumcontain in g alloys for brazing. In any case, cadm ium co n tain in g m etals m ust be appropriately segregated and labeled, so th a t w o rkers will not unknow ingly apply h eat to cadm ium . A ir volum es ta b u la te d for w elding258-" 0 are cal culated fo r a co n tro l velocity o f 100 feet/m in. For cadm ium fum e, control velocities o f 150 feet/m in should be used, so th a t volum es 50% g rea ter than th e tab u lated volum es should be used.
Local exh au st system s should be designed and o p erated in co n fo rm an ce w ith ANSI Z 9.2-1971, Effluent air should be cleaned, if necessary, to m eet any em ission standards th a t may be prom ul gated (th e re are now no EPA em issions standards for cadm ium ). Air from the exhaust ventilation system m ust n o t be recircu lated into the w ork place.
(e ) R espiratory P rotection F o r ad e q u ate respiratory p ro tectio n against the m any conditions th a t may be en co u n tered in in dividual o p erations, m any types o f respirators have been developed and approved. E ach has particular applications and lim itations from the standpoint o f p ro te ctio n , and each has its advantages and disad vantages from the standpoint o f operation and m aintenance. D etailed inform ation on the selec tion and use o f resp irators can be obtained from R espiratory P ro tective D evices M anual.2TM ANSI Z 8 8 .2 -1 9 6 9 259 also classifies, describes, and gives lim itations o f respirators.
R espirators fall into several classifications, ac cording to th eir m ode o f operation: (1 ) a t m osphere-supplying respirators, which include those to w hich suitable air is supplied by tanks carried by the w earer o r by a hose carrying air from a rem ote source (self-contained m asks, hose m asks, airline m asks, and com bination self-con tain ed and airline m asks); (2 ) air-purifying respira tors w hich filter o r absorb the contam inant (gas m ask with chem ical cartridge, particulate masks, and com bination m asks for gas, vapor, and p a r ticu late); and (3 ) com bination atm osphere-supply ing and air-purifying respirators. T he factors th at affect the overall perform ance of air-purifying respirators are the reliability of the face seal, the efficiency o f the filters, and o th e r variables such as leakage from exhalation valves.
T he applicable regulation on certification and approval o f respirators is 29 CFR 11. This requires, am ong o th e r things, th a t all air-purifying respirators approved for dusts and fumes with an environm ental limit less than 0.05 m g/cu m be equ ip p ed w ith a high efficiency filter.
(f) Protective C lothing P rotective clothing is n o t norm ally required for cadm ium operations. It is possible th at cadm ium dust co llected on clothing could be released into the air to cause a secondary exposure so th a t, if such clothing w ere w orn to the w o rk er's hom e, the w orker and oth ers m ight be exposed to cadm ium dust. T he b e tte r solution is to im prove w orkplace housekeeping to p rev en t clothing co n tam in atio n , but it seem s a wise p re c a u tio n th a t w ork clothing be changed at the end o f th e w orkshift and not carried hom e. T hus, th e re should be change room s with se p a ra te storage areas, such as lockers, and show er an d hand w ashing facilities should be p ro vided.
( W hile th ere isn 't good reason to believe th a t cadm ium co m pounds p e n e tra te the skin to a sig nificant extent, it is good p ractice to avoid skin c o n tac t and if c o n ta c t has o ccu rred to wash the af fected areas prom ptly.
(i) Storage C adm ium -containing, including cadm ium -plated, m etal parts should be k ep t sep arate from p arts not containing cadm ium so th a t accidental exposures resulting from w elding and cutting will not occur.
(j) E m ergency P ro ced u res E m ergency proced u res should be established for any ev ent th a t m ight result in substantial release of airb o rn e cadm ium . Such p ro c ed u res should in clude provisions to notify the attending physician th at exposure to high c o n ce n tratio n s of cadm ium fum e may cause lung edem a. T his edem a m ay not b ecom e evident until 8-24 hours a fter th e ex p o sure.
E m ergency p ro ce d u res should also include provision fo r a p p ro p riate resp irato rs specified in C h ap te r I.
It is im p o rtan t to design specific em ergency p ro c ed u res to be follow ed in the event of a fire, to p ro te c t both w orkers and firefighters.

# VII. COMPATIBILITY WITH OTHER STANDARDS
T h e E n vironm ental P ro te c tio n A gency has not classified cadm ium as a h azard o u s p o llu tan t and neith er em ission n o r am b ien t air stan d ard s have been issued.
EPA has n o t p ro m u lg ated solid w aste reg u la tions for cadm ium . H ow ever, it has reaffirm ed the 1962 PHS drinking w ater sta n d a rd o f 0.01 m g /liter279 as an interim prim ary drinking w ater regulation, applicable to com m unity w ater supplies ( Federal Register 4 0 :5 9 5 7 0 , D ec em b e r 24, 1975). W hile this stan d ard is fo r com m unity w ater sup plies, and thus is n o t directly applicable to discharge o f cadm ium into stream s, it seem s clear th a t disposal o f cadm ium w aste, liquid o r solid, should be in a m an n er n o t leading to its in tro d u c tion into drinking w ater. A rea sam ples may be tak en with the ap p a ra tu s used for determ ining w orker exposure, or w ith electro static precipitators.

# VIII. R EFER EN C ES
(b ) T he sam ple should be taken at a site representative o f the a rea being contam inated. The site should be identified for fu ture sampling.

# Calibration of Sampling Trains
T he ac cu rate calibration o f a sam pling pum p is essential for the c o rre c t in terp retatio n o f the volum e indicator. T he necessary frequency of calibration is d ep en d e n t on the use, care, and han dling to w hich the pum p has been subjected. In addition to the norm ally scheduled calibration, pum ps should be recalib rated if they have been subjected to m isuse, just received from a m anufac-tu re r, or ju st repaired. If the pum p receives hard usage, m ore freq u en t calib ratio n m ay be necessa- ( 1 ) W hile th e p u m p is running, the voltage o f th e p u m p b attery is m easu red w ith a voltm eter to assure th a t the b a tte ry is charg ed ad eq uately for calibration.
Place the cellulose m em brane filter with back u p pad in th e filter cassette.
(3 ) T he calib ratio n setup is assem bled as shown in Figure X IV -1.
(4 ) T he pum p is tu rn ed on and the inside of the soapbubble m ete r is m oistened by im m ersing the b u ret in the soap solution and draw ing bubbles up the tube until they are able to travel the entire length o f th e b u ret w ithout bursting.
(5 ) T he pum p is adjusted to provide a flow rate o f 2.0 liters/m in.
(6 ) T he w ater m an o m eter is ch eck ed to e n sure th at the pressure d ro p across the sam pling train does not exceed 13 conventional inches o f w ater (3.23 kP a) a t 2 liters/m in.
(7 ) A soapbubble is started up the b u re t and the tim e it tak es the bubble to travel a m inim um o f 1.0 liter is m easured with a sto p w atch.
(8 ) T he p ro c ed u re in ( 7) above is repeated at least th ree tim es, the results are averaged, and the flow rate is calculated by dividing the volum e betw een the p reselected m arks by the tim e req u ired for the soapbubble to travel the distance. (1 ) C o n c en tra te d nitric acid: redistilled or o f tra ce m etal quality. Use in subsequent steps w here nitric acid is designated.
(2 ) W ater: double distilled o r distilled deionized.
(3 ) S tandard cadm ium solution: 1000 /ng/ml. Dissolve 1.000 g o f m etallic cadm ium in nitric acid and dilute to 1 liter in a volum etric flask with sufficient w ater and nitric acid to yield a solution containing 10% nitric acid. This solution is com m ercially available.
(4 ) A tom ic absorption ap paratus with a cadm ium hollow c a th o d e lam p, read o u t accessory, and gas supply system . O perating conditions recom m ended by th e m a n u factu rer should be fol low ed for gas flow rates and o th er instrum ental variables. T he resonance line for cadm ium is 2,288 A ngstrom s.
(5 ) H ot p late, capable o f 300 C. (f) Q uality C ontrol E stablishm ent and m aintenance o f total analyti cal quality control system s to assure continued precision and accu racy o f laboratory reports in clude, as ap p ro p riate, these requirem ents:
(1 ) Each test m ust be ch ecked on each day o f use.
(2 ) A t least one standard (it may be an in stru m en t stan d ard ) and one control sam ple (w orking value established and run through the en tire analytical p ro c e d u re ) should be included with each run o f unknow n sam ples. W here the con tro l sam ple is not subject to th e in terferences in the unknow n sam ples, a previously run u n k nown should be in cluded as a blind ch eck sam ple. Sam ple, co ntrol sam ple (w orking value previ ously established by carrying through entire analytical p ro c e d u re ), and blank are placed in suitable acid-w ashed vessels. For personal sam plers em ploying 37 mm o r sim ilar filters, 50-ml G riffen b eak ers are suitable. N ext, 3 ml o f co n cen trated n itric acid is added and th e vessel is covered with a w atch glass. E ach sam ple is h eated on a hot plate in an exhaust hood until th e volum e o f nitric acid is red uced to approxim ately 0.5 ml and is pale yellow o r w ater w hite. F u rth er additions o f n itric acid may be necessary fo r com plete oxida tion o f the filter. T h e cooled sam ple is transferred to a suitable volum etric vessel, after rinsing the w atch glass. A 5-ml g raduated cylinder has been em ployed successfully. T he transfer and volum e ad justm ent are effected with 1% nitric acid solu tion.
T he resulting blank, c o n tro 1 a. d sam ple solu tions are aspirated into the flam e oi - .e instrum ent and the in strum ent response recorded. Sam ples m ay be diluted o r co n cen trated to correspond to the standards. If co n c en tratio n is necessary, the aspiration flow rate should be ch ecked to assure th a t it is com parable to those for the standards.

# Sulfosalicylic or Trichloroacetic Acid Analysis
F or analysis o f urine protein by precipitation w ith sulfosalicylic o r trich o ro acetic acid, the m ethods described by H enry e t al280 and Meulem ans281 can be used. M easure the specific gravity and the volum e o f the urine sam ple, and, after gentle mixing, filter ab o u t 75 ml; the sam ple should be at room tem p eratu re. C heck for the ap proxim ate co n ce n tra tio n o f protein by some p ro ce d u re such as use o f A lbustix If the esti m ated co n c en tratio n is higher than 150 m g /100 ml, dilute the sam ple with saline solution (0.99% ) to a p rotein c o n cen tratio n o f a b o u t 100 m g /100 ml.
Pipet 0.5 ml o f urine into each o f 2 tubes. A dd to the first tube 2 ml o f saline solution and to the o th e r 2 ml o f 3% sulfosalicylic acid or trich lo racetic acid. Mix the co n ten ts o f each tube im m ediately after th e addition and let stand for 5 m inutes, follow ed by a second mixing and reading o f the absorbance in a sp ectro p h o to m eter a t 620 nm against a reagent blank. S u b tract the reading o f the reagent blank and the reading o f the urine sam ple to w hich saline was ad ded from the reading of the reag en t-treated urine sam ple. C alculate the total am o u n t of p ro tein (p e r unit o f volum e o r per unit o f tim e such as 12 o r 24 h o u rs) from the sta n dard curve. A ccording to M cG arry e t al, 282 n o r mal urine p ro tein ex cretio n is a b o u t 70 m g/day but m ay be as high as 90 m g/day; th ese values are eq uivalent to 5 and 6.4 m g /100 ml if daily urine excretion is ab o u t 1,400 ml. C hem ical substances should be listed according to th e ir com plete nam e derived from a recognized system o f n o m enclature. W here possible, avoid using com m on nam es and general class nam es such as " arom atic am in e," " safety solvent," or " aliphatic h y d ro c a rb o n " w hen th e specific nam e is known.
T he " % " may be the approxim ate percentage by w eight o r volum e (indicate basis) w hich each hazardous in g redient o f the m ixture bears to the w hole m ixture. T his m ay be indicated as a range o r m axim um am o u n t, ie, " 10-40% vol" o r " 10% max w t" to avoid disclosure o f trad e secrets.
T oxic hazard d a ta shall be stated in term s o f co n c en tra tio n , m ode o f exposure o r test, and anim al used, ie, " 100 ppm L C 5 0 -rat," " 25 m g/kg L D 50-skin-rabbit," " 75 ppm LC m an ," or " perm issible exposure from 29 C FR 1910. (g) Section VII. Spill o r L eak P rocedures D etailed p ro c ed u res for cleanup and disposal should be listed w ith em phasis on precautions to be tak en to p ro te c t w orkers assigned to cleanup detail.
Specific neutralizing chem icals or p ro c ed u res should be described in detail. Disposal m ethods should be explicit including p ro p er label ing o f containers holding residues and ultim ate disposal m ethods such as " sanitary landfill," or " in cin eratio n ." W arnings such as " com ply with local, state, and federal antipollution o rd in an c es" a re p ro p er b u t n o t sufficient. P ertin en t specific local requirem ents shall be identified.
(h ) Section VIII. Special P rotection Inform a tion Section VIII requires specific inform ation. S tate m ents such as " Y es," " N o ," o r " If necessary" are n o t inform ative. V entilation requirem ents should be specific as to type and p referred m ethods. R espirators shall be specified as to type and NIOSH o r US B ureau o f M ines approval class, ie, " Supplied a ir," " O rganic vapor can ister," " Suitable for dusts n o t m ore toxic than lead ," etc. P rotective equipm ent m ust be specified as to type and m aterials o f construction.
(i) Section IX. Special Precautions " P recautionary S tate m e n ts" shall consist o f the label statem ents selected for use on the co ntainer o r placard. A dditional inform ation on any aspect o f safety o r health not covered in o th er sections should be inserted in Section IX. T he lower block can co ntain referen ces to published guides o r inhouse p ro cedures fo r handling and storage. D e p a rtm e n t o f T ra n sp o rtatio n m arkings and classifi cations and o th e r freight, handling, o r storage req u irem en ts and environm ental controls can be noted.
(j) Signature an d Filing A n o th e r im p o rta n t a re a is in v ascular effects o f cadm ium exposure, since th e re is conflicting in fo r m ation ore th e role o f cadm ium in hypertension and becau se o f suggestions th a t v ascular effects m ediate such o th e r effects as those on renal fu n c tion.
M ore evidence o n th e role o f cadm ium in d ev elo p m en t o f fetal ab n o rm alities in m an is needed. A dditional assu ran ce is n e e d e d th a t, if cadm ium ab so rp tio n is m ain tain ed at sufficiently low levels so th a t zinc availability to th e fetu s will not be a lte red , offspring o f cadm ium w o rkers will not be h arm ed by th e ir p a re n ts' exposure. In this co n n e c tio n , th e re is a n eed for a n atio n al surveil lance system th a t can g a th e r info rm atio n on fetal d eath s o r an om alies and erro rs in d ev elo p m en t o f child ren and relate these d a ta to o ccu p atio n al ex posures (o r o th e r en v iro n m en tal stresses) o f the parents.
T he p re se n t in ad eq u acies and conflicts in infor m ation, from both hu m an an d low er anim al in vestigations, on w h eth er cadm ium can cause m u ta tions o r c a n c e r should be c o rre c ted . F u rth er epidem iologic investigations in p o p u latio n s n o t ex posed to o th e r possible causes o f these effects should be pursued. A t the sam e tim e, life-time stu dies in experim ental anim als at ap p ro p riate doses should be p erform ed. T hese doses should be high enough to cause significant toxic effects from cad m ium b u t n o t so high as to cause a significant d ecrease in longevity, for d a ta to be properly in terp re ta b le. F u rth er evidence bearing on the sug gestion th a t cadm ium is involved in the causation o f p ro sta te c a n c e r should be ob tain ed , preferably from w o rk er populations n o t also exposed to o th e r possible carcinogens. In this con n ectio n , a m ortali ty study now underw ay a t th e K arolinska Institute may shed fu rth e r light on this question. This study o f w orker populations exposed to cadm ium in volves two co h o rts, one o f ab o u t 200 and the o th e r sm aller. E valuation o f th e d ata developed may be com pleted w ithin the year (L Friberg, ver bal com m unication, Ju n e 1976).
E vidence on adverse effects o f cadm ium on the nervous system , on the p ancreas, on the adrenals, and on thyroids and parathyroids should be c o n firm ed by additional investigations. In particular, conflicting inform ation on w hether cadm ium causes liver changes at w orkplace exposure co n c e n tra tio n s should be resolved.
F u rth e r investigation is also n eed ed on the sug gestion, developed in som e re cen t epidem iologic studies, th a t cadm ium w orkers who sm oke may have a g re ater risk o f developm ent o f altered renal function.
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# C E N T E R FO R D IS E A S E C O N T R O L N A T IO N A L IN S T IT U T E FOR O C C U P A T IO N A L S A F E T Y A N D H E A L T H R O B E R T A. T A F T L A B O R