ENVIRONMENTAL
RESEARCH
9, 152-158
(1975)
Biological Fate of a Single Administration of lglPt in Rats Following Different Routes of Exposure W. MOORE, W. CROCKER, National
JR., AND
D.
HYSELL,
J.
STARA
U. S. Environmental Protecfion Agency, OfJice of Research Environmenfal Research Center, Environmenfal Toxicology Cincinnati, Ohio Received
May
Development, Research Laboratory,
6, 1974
The retention, tissue distribution, and excretion of rglF’t in adult rats was determined following oral, intravenous (IV), and intratracheal administration. The highest retention was obtained following IV dosing, and lowest retention (less than 0.5%) occurred after oral dosing. Tissues containing the highest concentrations of islPt following IV administration were the kidney, adrenal, spleen, and liver. Following a single oral dose, almost all of the Y’t was excreted in the feces due to nonabsorption, whereas after IV dosing, similar quantities were excreted in both the urine and feces. Following IV dosing of pregnant rats, r9rPt was found in all the fetuses; however, the amount was small.
Automotive manufacturers have indicated that they will use the catalytic converter for reducing concentrations of carbon monoxide (CO) and total hydrocarbons (THC) emitted in automotive exhausts to comply with clean air mandates. With the use of the noble metal oxidation catalyst, there is the possibility that some of the platinum (Pt) or palladium (Pd) will be emitted to the atmosphere or enter other segments of the environment following degradation or disposal of worn-out converters. A number of investigators have reported on the toxicity of Pt compounds following occupational exposure. The term platinosis has been used to describe the respiratory or cutaneous reactions, either isolated or combined and allergic in nature, resulting from exposure to soluble Pt salts. Symptoms of both dermatologic and respiratory toxicity have been reported for a substantial number of workers exposed to complex Pt salts (Parrot et al., 1969; Roberts, 1951; Hunter et al., 1945). It has also been reported that 70% of the exposed staff of a platinum refinery had observable cases of platinosis (Herbert, 1966). Hunter et al. (1945) found that 52 of 91 employees of London platinum refineries had respiratory disturbances. Roberts (1951) opined that all workers exposed to platinum salts have some degree of platinosis; 60% of those he investigated were symptomatic and 40%, with no obvious symptoms, revealed evidence of involvement such as irritated conjunctivae and hypertrophy of the respiratory lymphatics. In addition to workers in platinum refineries, workers who handle paper containing potassium chloroplatinate in photography have reported skin reactions (Karasek et al., 1911). Scratch tests on human subjects provided information suggesting that sensitiv152 Copyright All rights
0 1975 by Academic Press, Inc. of reproduction in any form reserved.
FATE
OF
lglPt
IN
RATS
153
ity to platinum salts is an acquired reaction precipitated by previous exposure. Before being employed in a platinum refinery, none of the 24 subjects were’sensitive to the test solution above 1: 100 dilution. Following employment, workers who showed no signs of platinosis remained insensitive to dilutions above 1: 100. Subjects with definite signs of platinosis, however, had. positive responses to dilutions of 1: lo3 to 1: 108. The degree of sensitivity correlated more or less with the severity of the subject’s symptoms (Roberts, 1951). Sodium chloroplatinate, a complex platinum salt frequently encountered in industry, has been tested in both rats and guinea pigs (Saindelle et al., 1969; Parrot et nl., 1969). Immediately upon the intravenous injection of 20 mg/kg sodium chloroplatinate into a guinea pig, an intense attack of asthma occurred and death resulted within 3 minutes. Autopsy revealed the lungs to be pale and inflated as in anaphylactic shock. The injection of 1 to 2 mg/kg resulted in bronchospasm comparable to that caused by 3 pg/kg of histamine. Repeated injections of histamine resulted in reproducible changes in bronchial motility, whereas sodium chloroplatinate exhibited tachyphylaxis upon repeated injection. Aerosol exposure of guinea pigs to sodium chloroplatinate also resulted in an intense asthma attack. Administration of the antihistamine pysilimine completely blocked the action of sodium chloroplatinate. When compared with the reaction of histamine, the reaction following exposure to sodium chloroplatinate has a long latent period (45 seconds following IV injection and 15 seconds following application to guinea pig ileum). This long latent period, along with the observed tachyphylaxis, suggests that platinum salts do not act by themselves but, rather, are involved in the release of a substance from the tissues. Evidence that chloroplatinate may be causing the release of histamine is seen from the fact that 10 minutes after the intracardiac injection of 40 mg/kg of sodium chloroplatinate into rats, the plasma histamine dichloroplatinate level rose to 1500 hg/l from a norm of 150 pg/l. The amount of information available on the metabolism, biological fate, and relative toxicity of the platinum salts is extremely limited. With the possibility that platinum may be emitted to the atmosphere and because of the proven toxicity of certain platinum compounds, The Environmental Toxicology Research Laboratory of the National Environmental Research Center in Cincinnati, Ohio, is investigating the significance of different routes of exposure on excretion, and biological fate. METHODS
Animals and Treatments The outbred albino rats (Charles River CD-l strain) used in this study were maintained on a commercial diet (Purina Lab Chow) and tap water ad libitum except where otherwise noted. The three treatment groups consisted of: 1. Intratracheal administration. Fourteen fasted male rats, 180-200 g, were anesthetized with pentobarbital sodium and placed in dorsal recumbency. The trachea was isolated through a ventral midline cervical incision and blunt dissection of the overlying musculature. lslPt (25 $Zi in 0.1 ml saline)
154
MOORE
ET
AL.
was injected intratracheally with a l-cc tuberculin syringe and a 5/8-in., 25-ga. needle. After the incision was closed, the animals were housed in hanging wire cages, and used for determination of whole body retention of 191pt. 2. Oral administration. Seventy-one fasted male rats, 180-200 g, were lightly anesthetized with ether and given 25 ,&i of lslPt in 0.2 ml saline by stomach tube. Six rats were placed in metabolism cages for collection of 24-hour urine and feces samples to determine routes of excretion. Fifteen animals were used for whole body determinations. Ten rats were sacrificed on days 1, 2, 3, 7, and 14 after dosing to establish organ distribution of lglPt. Fifteen nonfasted suckling rats, approximately 30 g, were given a single dose of 25 &i of lslPt by stomach tube. These animals were used to compare their retention with retention of Pt in adult rats. 3. Intravenous administration. Seventy male rats, 180-200 g, were given 25 &i lslPt in 0.1 ml saline IV in a tail vein with a l-cc tuberculin syringe and S/g-in., 25-ga. needle. Six rats were placed in metabolism cages for collection of 24-hour urine and feces samples, and 15 animals were used for whole body determinations. Ten rats were sacrificed on days 1, 2, 3, 7, and 14 after dosing to establish organ distribution of lglPt. An additional 15 pregnant rats (18th-day gestation) were given 25 &i lglPt IV and sacrificed 24 hours later to determine placental transfer and organ distribution. Sacrifice and Tissue Sampling All rats were euthanatized with an overdose of chloroform anesthesia. Samples collected routinely for radioactive counting were the blood, heart, lung, liver, kidney, adrenal, pancreas, abdominal fat, spleen, skeletal muscle, bone, brain, and testicle from males, ovary from females. In the pregnant females, four placentas, four fetuses, and a pooled sample of fetal livers were taken from each litter for counting. Radioactive
Determinations
A carrier-free solution of 1s1,‘s~tf4 in 1~ HCl was used for this study. The lglPt isotope comprised at least 50% of the total radioactive Pt, and the 0.539 meV gamma of *glPt was counted in the radioactive determinations. lglPt has a 3-day half-life. Immediately after dosing, whole body counts were made on all animals used in the retention studies. The animals were counted daily for the first few days and then every other day for the duration of the experiment. A 200-channel gamma spectrometer with a 5-in. NaI (Tl) crystal was used for whole body counts. Tissue, urine, and feces samples were counted in a well-type refrigerated, scintillation spectrometer. RESULTS
Whole Body Retention Whole body retention of lglPt following a single dose was affected significantly by the route of administration. The percent of Ig’Pt retained with time following three different routes of administration is presented in Fig. 1. Following oral
FATE
OF
lglPt
IN
155
RATS
Suckling Oml
Rat
20 r
0
4
8 12 lb Days After
20 24 Dosing
28
32
10 0L 4 .
FIG. 1. Whole body retention of ly’Pt in adult rats following oral, IV, and intratracheal administrdrats following oral administration. tion. Also shown is whole body retention of lglPt in suckling
dosing, the total net gastointestinal excretion was extremely high; the retention curve rapidly declined to less than 1% at the end of 3 days. Retention of lglPt by suckling rats following oral administration was similar to that of the adults although the amount retained at 24 hours was higher (14.7% for the suckling rats vs. 7.4% for the adults). The difference in whole body retention probably is due in part, to a difference in the rate of movement of the lglPt through the gastrointestinal tract. The amount of lglPt retained in the lungs following intratracheal dosing was significantly higher than that for oral dosing. The excretion of approximately 50% of the initial dose during the first 24 hours is attributed to mucociliary and alveolar clearance. Whole body retention of lglPt was the highest following IV dosing; the short half-life precluded an accurate determination of the biological half-life for this metal.
Radioactive counts of lglPt orally indicated that only a small amount was whole body data showing lowing IV administration, urine contained a greater
24-hour urine and feces samples from rats receiving almost all of the iglPt was eliminated in the feces and excreted in the urine (Fig. 2). These values support the that total net gastrointestinal absorption was low. FollglPt was excreted in both the urine and feces. The quantity of the l9lPt.
Tisslre Distribution
The distribution and concentration of lglPt was determined for different organs as a function of time following oral and IV dosing. After oral dosing, the kidney
156
MOORE
FIG.
2. Excretion
ET
of lslPt following
AL.
IV and oral administration.
and liver contained the highest concentrations of lslPt. The amount of radioactivity found in the other organs was not significantly higher than that of the background. The amount of lslPt found in selected tissues and the percent of the initial dose per gram following IV dosing are presented in Table 1. Most of the tissues did not contain levels of lslPt appreciably higher than that found in blood. However, the fraction of lslPt in the plasma that is in an “available” form for movement into the various tissues was not determined. The large amount of lslPt found in the kidney suggests that this organ accumulates this element. Concentrations higher than the blood values were also found in the liver, spleen, and TABLE lglP~
PRESENT
IN RATS
1 day
Tissue Blood Heart Lung Liver Kidney Spleen Pancreas Bone Brain Fat Testis Adrenal Muscle Duodenal
segment
FOLLOWING
1 A SINGLE
2 days
INTRAVENOUS
DOSE
7 days
c/g wet weight
%per gram
clg wet weight
%per gram
22,147 11,819 18,432 36,848 162.227 41,085 22,208 13,146 1,150 4,487 4,186 45,439 4,798 12.725
0.91 0.48 0.75 1.51 6.65 1.68 0.91 0.53 0.05 0.18 0.17 1.86 0.19 0.52
19.732 12,201 16,139 31,274 160.656 45,840 19,487 12,800 2,485 4,501 6,540 42,363 4,671 6,044
0.81 0.50 0.66 1.28 6.59 1.89 0.80 0.52 0.10 0.18 0.27 1.74 0.19 0.25
14 days
c/g wet weight
% per gram
c/g wet weight
% per gram
12,774 8,805 11,180 25.732 138,010 55,764 14.802 8,932 595 3,201 3.873 26,667 3,441 4,031
0.52 0.36 0.46 1.05 5.66 2.29 0.60 0.37 0.02 0.13 0.16 1.09 0.14 0.16
7,921 4,593 5,770 4,733 30,195 20,973 3,973 5,440 265 429 1,431 6.190 2,146 1.410
0.32 0.19 0.24 0.19 1.24 0.86 0.16 0.22 0.01 0.02 0.06 0.25 0.09 0.06
FATE
OF
lglPt
IN
TABLE 2 lQIP~ IN MATERNAL ORGANS
Tissue Blood Lung Liver Kidney Bone Brain Ovary Placenta Fetus Fetal liver
Mean counts per gram 10,568 17.981 43.375 127,064 9,193 792 14,639 27,750 432 1,421
157
RATS
AND FETUSES % of dose per gram 0.35 0.60 1.44 4.22 0.30 0.02 0.49 0.92 0.01 0.05
adrenal. The relative low count for the brain indicated that lglPt was transferred through the blood-brain barrier only to a limited extent. MaternallFetal
Uptake
Fifteen pregnant rats (l&h-day gestation) were given 25 &i lQIPt IV and sacrificed 24 hours later to determine placental transfer. During the 24-hour period, the pregnant rats excreted 18.8% of the initial dose. The amount excreted by the pregnant rats was approximately the same as the amount (19.3%) excreted by the adult male rats during the first 24-hour period. The concentration of lQIPt per gram for different maternal tissues and fetuses is given in Table 2. The data indicated that there was some transplacental passage of lg*Pt; however, there appeared to be placental binding or accumulation. lglPt was pre-. sent in all the fetuses (60) counted. The hemochorial placental barrier of rats is probably more easily traversed than the more complex placental barriers found in other species of experimental animals. DISCUSSION
With the widespread use of catalytic converters, the possibility exists that metallic Pt or one or more chemical forms of Pt may be emitted to atmosphere during use or escape the converter at the time of disposal. Since the ecological and biological fate of Pt has not been investigated, there is no information from which to evaluate the impact of this metal upon the general health and well-being of the populace if it was released into the environment. In comparison to lead which is a widespread environmental pollutant, the acute toxicity of Pt, based on the LD,,, is much greater. The threshold limit value (TLV) for inorganic compounds of Pb is 0.2 mg/m3 and for soluble Pt is 0.002 mg/m3. The toxicity of Pt is influenced by the chemical form; the chemical forms of Pt associated with automotive emissions and the chemical forms that may exist in the environment have not been adequately identified, however. Although there would be some dermal exposure, ingestion and inhalation
158
MOORE
ET
AL.
would probably comprise the two major routes of human exposure to Pt. The results of this study indicate that Pt is not readily absorbed following ingestion although additional information is needed for a number of species before a general conclusion can be made. The data also suggest that absorption may be slightly higher in the .very young. Following introduction of the Pt into the trachea, the data indicate that a greater quantity of the Pt was retained. Preliminary findings on an acute inhalation study currently in progress at this laboratory show somewhat more lglPt retained following this mode of exposure, and the distribution of lglPt was similar to that following intravenous injection. Since platinosis is an allergic disease, it is important to consider whether chronic exposure to Pt salts if they should be released into ambient atmosphere will cause platinosis or result in aggravation of preexisting asthmatic or cardiorespiratory deficiencies in man. In the past, human exposures have been limited to a small number of industrial workers and the concentration of Pt salts required to produce platinosis has not been determined. If a large number of catalytic converters are used and if the Pt is released, the question arises will the Pt or Pd compounds that enter the environment create a potential health problem. To ascertain the impact of the expanded use of these metals, it is obvious that additional information is needed on their biological effects and ecological fate. REFERENCES Herbert, R. (1966). Affections provoquees par 877-886. Hunter. 0.. Milton, R., Perry, K. M. A. (1945). Brit. J. Industr. Med. 2, 92-98. Karasek, S. R., and Karasek. M. (1911). The use sion of Occupational Disease, p. 97. Parrot, J. L., Herbert, R.. Saindelle. A., Ruff. Health 19, 685691. Roberts. A. E. (1951). Platinosis. Arch. Itzdtutr. Saindelle. A.. Ruff. F. (1969). Histamine release 313-321.
les
composes
Asthma
du platine.
caused
of platinum
paper,
F. (1969).
Platinum
Arch.
Ma/.
by the complex Report
Hyg. 4, 549-559. by sodium chloroplatinate.
Brit.
27,
salts of platinum.
of Illinois
and platinosis.
Proj:
State CommisArch.
Environ.
J. Pharrnaco/.
35,
RESEARCH
9, 152-158
(1975)
Biological Fate of a Single Administration of lglPt in Rats Following Different Routes of Exposure W. MOORE, W. CROCKER, National
JR., AND
D.
HYSELL,
J.
STARA
U. S. Environmental Protecfion Agency, OfJice of Research Environmenfal Research Center, Environmenfal Toxicology Cincinnati, Ohio Received
May
Development, Research Laboratory,
6, 1974
The retention, tissue distribution, and excretion of rglF’t in adult rats was determined following oral, intravenous (IV), and intratracheal administration. The highest retention was obtained following IV dosing, and lowest retention (less than 0.5%) occurred after oral dosing. Tissues containing the highest concentrations of islPt following IV administration were the kidney, adrenal, spleen, and liver. Following a single oral dose, almost all of the Y’t was excreted in the feces due to nonabsorption, whereas after IV dosing, similar quantities were excreted in both the urine and feces. Following IV dosing of pregnant rats, r9rPt was found in all the fetuses; however, the amount was small.
Automotive manufacturers have indicated that they will use the catalytic converter for reducing concentrations of carbon monoxide (CO) and total hydrocarbons (THC) emitted in automotive exhausts to comply with clean air mandates. With the use of the noble metal oxidation catalyst, there is the possibility that some of the platinum (Pt) or palladium (Pd) will be emitted to the atmosphere or enter other segments of the environment following degradation or disposal of worn-out converters. A number of investigators have reported on the toxicity of Pt compounds following occupational exposure. The term platinosis has been used to describe the respiratory or cutaneous reactions, either isolated or combined and allergic in nature, resulting from exposure to soluble Pt salts. Symptoms of both dermatologic and respiratory toxicity have been reported for a substantial number of workers exposed to complex Pt salts (Parrot et al., 1969; Roberts, 1951; Hunter et al., 1945). It has also been reported that 70% of the exposed staff of a platinum refinery had observable cases of platinosis (Herbert, 1966). Hunter et al. (1945) found that 52 of 91 employees of London platinum refineries had respiratory disturbances. Roberts (1951) opined that all workers exposed to platinum salts have some degree of platinosis; 60% of those he investigated were symptomatic and 40%, with no obvious symptoms, revealed evidence of involvement such as irritated conjunctivae and hypertrophy of the respiratory lymphatics. In addition to workers in platinum refineries, workers who handle paper containing potassium chloroplatinate in photography have reported skin reactions (Karasek et al., 1911). Scratch tests on human subjects provided information suggesting that sensitiv152 Copyright All rights
0 1975 by Academic Press, Inc. of reproduction in any form reserved.
FATE
OF
lglPt
IN
RATS
153
ity to platinum salts is an acquired reaction precipitated by previous exposure. Before being employed in a platinum refinery, none of the 24 subjects were’sensitive to the test solution above 1: 100 dilution. Following employment, workers who showed no signs of platinosis remained insensitive to dilutions above 1: 100. Subjects with definite signs of platinosis, however, had. positive responses to dilutions of 1: lo3 to 1: 108. The degree of sensitivity correlated more or less with the severity of the subject’s symptoms (Roberts, 1951). Sodium chloroplatinate, a complex platinum salt frequently encountered in industry, has been tested in both rats and guinea pigs (Saindelle et al., 1969; Parrot et nl., 1969). Immediately upon the intravenous injection of 20 mg/kg sodium chloroplatinate into a guinea pig, an intense attack of asthma occurred and death resulted within 3 minutes. Autopsy revealed the lungs to be pale and inflated as in anaphylactic shock. The injection of 1 to 2 mg/kg resulted in bronchospasm comparable to that caused by 3 pg/kg of histamine. Repeated injections of histamine resulted in reproducible changes in bronchial motility, whereas sodium chloroplatinate exhibited tachyphylaxis upon repeated injection. Aerosol exposure of guinea pigs to sodium chloroplatinate also resulted in an intense asthma attack. Administration of the antihistamine pysilimine completely blocked the action of sodium chloroplatinate. When compared with the reaction of histamine, the reaction following exposure to sodium chloroplatinate has a long latent period (45 seconds following IV injection and 15 seconds following application to guinea pig ileum). This long latent period, along with the observed tachyphylaxis, suggests that platinum salts do not act by themselves but, rather, are involved in the release of a substance from the tissues. Evidence that chloroplatinate may be causing the release of histamine is seen from the fact that 10 minutes after the intracardiac injection of 40 mg/kg of sodium chloroplatinate into rats, the plasma histamine dichloroplatinate level rose to 1500 hg/l from a norm of 150 pg/l. The amount of information available on the metabolism, biological fate, and relative toxicity of the platinum salts is extremely limited. With the possibility that platinum may be emitted to the atmosphere and because of the proven toxicity of certain platinum compounds, The Environmental Toxicology Research Laboratory of the National Environmental Research Center in Cincinnati, Ohio, is investigating the significance of different routes of exposure on excretion, and biological fate. METHODS
Animals and Treatments The outbred albino rats (Charles River CD-l strain) used in this study were maintained on a commercial diet (Purina Lab Chow) and tap water ad libitum except where otherwise noted. The three treatment groups consisted of: 1. Intratracheal administration. Fourteen fasted male rats, 180-200 g, were anesthetized with pentobarbital sodium and placed in dorsal recumbency. The trachea was isolated through a ventral midline cervical incision and blunt dissection of the overlying musculature. lslPt (25 $Zi in 0.1 ml saline)
154
MOORE
ET
AL.
was injected intratracheally with a l-cc tuberculin syringe and a 5/8-in., 25-ga. needle. After the incision was closed, the animals were housed in hanging wire cages, and used for determination of whole body retention of 191pt. 2. Oral administration. Seventy-one fasted male rats, 180-200 g, were lightly anesthetized with ether and given 25 ,&i of lslPt in 0.2 ml saline by stomach tube. Six rats were placed in metabolism cages for collection of 24-hour urine and feces samples to determine routes of excretion. Fifteen animals were used for whole body determinations. Ten rats were sacrificed on days 1, 2, 3, 7, and 14 after dosing to establish organ distribution of lglPt. Fifteen nonfasted suckling rats, approximately 30 g, were given a single dose of 25 &i of lslPt by stomach tube. These animals were used to compare their retention with retention of Pt in adult rats. 3. Intravenous administration. Seventy male rats, 180-200 g, were given 25 &i lslPt in 0.1 ml saline IV in a tail vein with a l-cc tuberculin syringe and S/g-in., 25-ga. needle. Six rats were placed in metabolism cages for collection of 24-hour urine and feces samples, and 15 animals were used for whole body determinations. Ten rats were sacrificed on days 1, 2, 3, 7, and 14 after dosing to establish organ distribution of lglPt. An additional 15 pregnant rats (18th-day gestation) were given 25 &i lglPt IV and sacrificed 24 hours later to determine placental transfer and organ distribution. Sacrifice and Tissue Sampling All rats were euthanatized with an overdose of chloroform anesthesia. Samples collected routinely for radioactive counting were the blood, heart, lung, liver, kidney, adrenal, pancreas, abdominal fat, spleen, skeletal muscle, bone, brain, and testicle from males, ovary from females. In the pregnant females, four placentas, four fetuses, and a pooled sample of fetal livers were taken from each litter for counting. Radioactive
Determinations
A carrier-free solution of 1s1,‘s~tf4 in 1~ HCl was used for this study. The lglPt isotope comprised at least 50% of the total radioactive Pt, and the 0.539 meV gamma of *glPt was counted in the radioactive determinations. lglPt has a 3-day half-life. Immediately after dosing, whole body counts were made on all animals used in the retention studies. The animals were counted daily for the first few days and then every other day for the duration of the experiment. A 200-channel gamma spectrometer with a 5-in. NaI (Tl) crystal was used for whole body counts. Tissue, urine, and feces samples were counted in a well-type refrigerated, scintillation spectrometer. RESULTS
Whole Body Retention Whole body retention of lglPt following a single dose was affected significantly by the route of administration. The percent of Ig’Pt retained with time following three different routes of administration is presented in Fig. 1. Following oral
FATE
OF
lglPt
IN
155
RATS
Suckling Oml
Rat
20 r
0
4
8 12 lb Days After
20 24 Dosing
28
32
10 0L 4 .
FIG. 1. Whole body retention of ly’Pt in adult rats following oral, IV, and intratracheal administrdrats following oral administration. tion. Also shown is whole body retention of lglPt in suckling
dosing, the total net gastointestinal excretion was extremely high; the retention curve rapidly declined to less than 1% at the end of 3 days. Retention of lglPt by suckling rats following oral administration was similar to that of the adults although the amount retained at 24 hours was higher (14.7% for the suckling rats vs. 7.4% for the adults). The difference in whole body retention probably is due in part, to a difference in the rate of movement of the lglPt through the gastrointestinal tract. The amount of lglPt retained in the lungs following intratracheal dosing was significantly higher than that for oral dosing. The excretion of approximately 50% of the initial dose during the first 24 hours is attributed to mucociliary and alveolar clearance. Whole body retention of lglPt was the highest following IV dosing; the short half-life precluded an accurate determination of the biological half-life for this metal.
Radioactive counts of lglPt orally indicated that only a small amount was whole body data showing lowing IV administration, urine contained a greater
24-hour urine and feces samples from rats receiving almost all of the iglPt was eliminated in the feces and excreted in the urine (Fig. 2). These values support the that total net gastrointestinal absorption was low. FollglPt was excreted in both the urine and feces. The quantity of the l9lPt.
Tisslre Distribution
The distribution and concentration of lglPt was determined for different organs as a function of time following oral and IV dosing. After oral dosing, the kidney
156
MOORE
FIG.
2. Excretion
ET
of lslPt following
AL.
IV and oral administration.
and liver contained the highest concentrations of lslPt. The amount of radioactivity found in the other organs was not significantly higher than that of the background. The amount of lslPt found in selected tissues and the percent of the initial dose per gram following IV dosing are presented in Table 1. Most of the tissues did not contain levels of lslPt appreciably higher than that found in blood. However, the fraction of lslPt in the plasma that is in an “available” form for movement into the various tissues was not determined. The large amount of lslPt found in the kidney suggests that this organ accumulates this element. Concentrations higher than the blood values were also found in the liver, spleen, and TABLE lglP~
PRESENT
IN RATS
1 day
Tissue Blood Heart Lung Liver Kidney Spleen Pancreas Bone Brain Fat Testis Adrenal Muscle Duodenal
segment
FOLLOWING
1 A SINGLE
2 days
INTRAVENOUS
DOSE
7 days
c/g wet weight
%per gram
clg wet weight
%per gram
22,147 11,819 18,432 36,848 162.227 41,085 22,208 13,146 1,150 4,487 4,186 45,439 4,798 12.725
0.91 0.48 0.75 1.51 6.65 1.68 0.91 0.53 0.05 0.18 0.17 1.86 0.19 0.52
19.732 12,201 16,139 31,274 160.656 45,840 19,487 12,800 2,485 4,501 6,540 42,363 4,671 6,044
0.81 0.50 0.66 1.28 6.59 1.89 0.80 0.52 0.10 0.18 0.27 1.74 0.19 0.25
14 days
c/g wet weight
% per gram
c/g wet weight
% per gram
12,774 8,805 11,180 25.732 138,010 55,764 14.802 8,932 595 3,201 3.873 26,667 3,441 4,031
0.52 0.36 0.46 1.05 5.66 2.29 0.60 0.37 0.02 0.13 0.16 1.09 0.14 0.16
7,921 4,593 5,770 4,733 30,195 20,973 3,973 5,440 265 429 1,431 6.190 2,146 1.410
0.32 0.19 0.24 0.19 1.24 0.86 0.16 0.22 0.01 0.02 0.06 0.25 0.09 0.06
FATE
OF
lglPt
IN
TABLE 2 lQIP~ IN MATERNAL ORGANS
Tissue Blood Lung Liver Kidney Bone Brain Ovary Placenta Fetus Fetal liver
Mean counts per gram 10,568 17.981 43.375 127,064 9,193 792 14,639 27,750 432 1,421
157
RATS
AND FETUSES % of dose per gram 0.35 0.60 1.44 4.22 0.30 0.02 0.49 0.92 0.01 0.05
adrenal. The relative low count for the brain indicated that lglPt was transferred through the blood-brain barrier only to a limited extent. MaternallFetal
Uptake
Fifteen pregnant rats (l&h-day gestation) were given 25 &i lQIPt IV and sacrificed 24 hours later to determine placental transfer. During the 24-hour period, the pregnant rats excreted 18.8% of the initial dose. The amount excreted by the pregnant rats was approximately the same as the amount (19.3%) excreted by the adult male rats during the first 24-hour period. The concentration of lQIPt per gram for different maternal tissues and fetuses is given in Table 2. The data indicated that there was some transplacental passage of lg*Pt; however, there appeared to be placental binding or accumulation. lglPt was pre-. sent in all the fetuses (60) counted. The hemochorial placental barrier of rats is probably more easily traversed than the more complex placental barriers found in other species of experimental animals. DISCUSSION
With the widespread use of catalytic converters, the possibility exists that metallic Pt or one or more chemical forms of Pt may be emitted to atmosphere during use or escape the converter at the time of disposal. Since the ecological and biological fate of Pt has not been investigated, there is no information from which to evaluate the impact of this metal upon the general health and well-being of the populace if it was released into the environment. In comparison to lead which is a widespread environmental pollutant, the acute toxicity of Pt, based on the LD,,, is much greater. The threshold limit value (TLV) for inorganic compounds of Pb is 0.2 mg/m3 and for soluble Pt is 0.002 mg/m3. The toxicity of Pt is influenced by the chemical form; the chemical forms of Pt associated with automotive emissions and the chemical forms that may exist in the environment have not been adequately identified, however. Although there would be some dermal exposure, ingestion and inhalation
158
MOORE
ET
AL.
would probably comprise the two major routes of human exposure to Pt. The results of this study indicate that Pt is not readily absorbed following ingestion although additional information is needed for a number of species before a general conclusion can be made. The data also suggest that absorption may be slightly higher in the .very young. Following introduction of the Pt into the trachea, the data indicate that a greater quantity of the Pt was retained. Preliminary findings on an acute inhalation study currently in progress at this laboratory show somewhat more lglPt retained following this mode of exposure, and the distribution of lglPt was similar to that following intravenous injection. Since platinosis is an allergic disease, it is important to consider whether chronic exposure to Pt salts if they should be released into ambient atmosphere will cause platinosis or result in aggravation of preexisting asthmatic or cardiorespiratory deficiencies in man. In the past, human exposures have been limited to a small number of industrial workers and the concentration of Pt salts required to produce platinosis has not been determined. If a large number of catalytic converters are used and if the Pt is released, the question arises will the Pt or Pd compounds that enter the environment create a potential health problem. To ascertain the impact of the expanded use of these metals, it is obvious that additional information is needed on their biological effects and ecological fate. REFERENCES Herbert, R. (1966). Affections provoquees par 877-886. Hunter. 0.. Milton, R., Perry, K. M. A. (1945). Brit. J. Industr. Med. 2, 92-98. Karasek, S. R., and Karasek. M. (1911). The use sion of Occupational Disease, p. 97. Parrot, J. L., Herbert, R.. Saindelle. A., Ruff. Health 19, 685691. Roberts. A. E. (1951). Platinosis. Arch. Itzdtutr. Saindelle. A.. Ruff. F. (1969). Histamine release 313-321.
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