Why chromium ions don't really worry me (long and boring)

[Guest guest]

I think we all owe Steve a debt of gratitude for his exposition about the ion

issue.

Yay, Steve.

Des Tuck

Full of chrome (and other things too)

In a message dated 1/17/2004 11:28:25 AM Pacific Standard Time,

sog@... writes:

So, even though there's no long-term data on the safety of resurfacing

(and it's important to remember that there isn't), I'm personally not

real worried about the issue. I'm not going to take a multivitamin

containing chromium after surgery, but I'm not going to worry about it.

[Guest guest]

Like everyone else here, from the moment I heard about resurfacing, I

also began to hear concerns about metal ion (and specifically chromium)

exposure due to wear of the metal-on-metal implant. I thought I'd see

if I could make a rough calculation of how severe this possible exposure

might be, based on publicly available information. This back-of-the

envelope assessment follows.

First, some background chemistry:

Chromium ions come in two flavors: hexavalent (missing 6 electrons) Chromium,

which is extremely toxic, and trivalent (missing 3 electrons) Chromium, which

is comparatively benign stuff. All the ions shed by the implants are

trivalent chromium, to which the following data apply.

Wear tests of the Corin Cormet 2000 resurfacing implant show the following

(see www.cormet.com/wear.asp):

During the initial breakin period, the Cormet implant (the only one for

which I could locate detailed wear simulation data on the net)

experiences an average volumetric wear rate of approximately 2.4 cubic

mm per million cycles (steps), dropping to 0.4 cubic mm/Mcycle

thereafter.

According to a 1998 paper in the _Journal of Bone and Joint

Surgery_(1), the average hip or knee replacement patient patient puts

900,000 cycles/year on the hip/knee after surgery. Let's call it 1

million cycles, just to simplify things later. I should note that the

most active subject in this study did 3.2 million cycles, and the least

active did a mere 70,000, so there's an awful lot of variability in

this data.

The alloy (F75) used for these implants is 66% Cobalt, 28% Chromium,

and 6% Molybdenum so this wear debris is about 28% Chromium. This isn't

strictly accurate, since the alloy is 28% Chromium by weight, rather

than by volume, but this is close enough for government work.

The density of chromium is 7140 kg/cubic meter, or 7.14 mg/cu mm.

So, by my calculation, the amount of chromium being dumped into your

system is, roughly:

2.4 cu mm/megacycle * 7.14 mg/ cu mm * 1 megacycle/year = 17.136 mg/year =

46.95 micrograms/day.

This drops to 7.83 micrograms/day after the breakin period.

To put this in perspective, a Centrum® multivitamin tablet contains

120 micrograms, which happens to be the RDA for chromium. This is nearly

2.6 times the amount produced by the implant during the breakin phase,

and 15 times the dose delivered by the implant thereafter. This isn't

a fair comparison, because your gut doesn't absorb chromium real

well, but I'll deal with that later.

One measure of long-term toxicity is the " chronic reference dose " ,

which is defined as " an estimate of a daily exposure level for the

human population, including sensitive subpopulations, that is likely to

be without an appreciable risk of deleterious effects during a

lifetime " (http://www.nbc-med.org/SiteContent/glossary.asp).

According to the toxicity profile for chromium in the Oak Ridge

National Laboratory Risk Assessment Information System

(http://risk.lsd.ornl.gov/tox/profiles/Chromium_ragsa.shtml) the

chronic reference dose for trivalent chromium is 1.5mg/kg-day, which in

my case (~75kg mass) is 112.5 mg/day, or roughly 2400 times the amount

shed by the implant during the breakin period, and 14377 times the

amount produced thereafter. However, according to the same toxicity

profile, only 0.5% of orally ingested trivalent chromium makes it into

your bloodstream. Correcting for this, a Cormet implant should give me

the equivalent of 8.3% of the chronic reference dose during the breakin

period and 1.4% thereafter if every last bit of chromium it produces

dissolves and goes into my bloodstream (this isn't the case, but it's the

absoloute worst scenario). I should note that there's a factor of

10 uncertainty in the chronic reference dose, and that some people

are allergic to chromium (so these figures don't apply to them -

if you're allergic to metals, you probably shouldn't have any kind

of metal-on-metal joint replacement).

So, even though there's no long-term data on the safety of resurfacing

(and it's important to remember that there isn't), I'm personally not

real worried about the issue. I'm not going to take a multivitamin

containing chromium after surgery, but I'm not going to worry about it.

Steve

(1) Schmalzried, Szuszczewicz, Northfield, Akizuki, el, Belcher,

and Amstutz; " Quantitative Assessment of Walking Activity after

Total Hip or knee Replacement " , JBJS 80:54-9(1998).

[Guest guest]

Steve thanks for the most coherent analysis of the " ion " issue I've seen to

date. I hope you'll re-post it whenever the question arises in the future.

Mike Trautman

C2K, Kennedy, Sep 03

[Guest guest]

Cobalt is more toxic than chromium and is also a higher percentage of

the alloy used. If you go thru the same calcs for cobalt, you will

find that the safety factor is about 1-order of magnitude less. I did

these same calcs a couple years ago and came to the same conclusion.

One interesting thing is that while cobalt is a higher percentage in

the implant alloy, the typical serum and urine ion levels of chromium

are 50% to 2-times higher than cobalt. My guess is that cobalt is

harder, therefore chromium is preferentially eroded in the bearing.

bilat C+ July 2001, metal ion study participant

[Guest guest]

> Cobalt is more toxic than chromium and is also a higher percentage of

> the alloy used. If you go thru the same calcs for cobalt,

Where did you get a toxicity information for cobalt?

According to the EPA website:

" Human studies are inconclusive regarding inhalation exposure to

cobalt and cancer, and the one available oral study did not report a

correlation between cobalt in the drinking water and cancer deaths.

EPA has not classified cobalt for carcinogenicity. "

and

" EPA has not established a Reference Concentration (RfC) or a

Reference Dose (RfD) for cobalt. "

The DOE Risk Assessment Information System also has no information

on cobalt. The California EPA has a recommended respiratory exposure

level, since inhaled cobalt is a lung irritant, but they don't

have any toxicity data, either.

I couldn't find the data to make the same calculation for cobalt.

If I could've, I would've.

> you will

> find that the safety factor is about 1-order of magnitude less.

I did find one agricultural study that said that sheep can tolerate

a chronic oral dose of 352 milligrams/100kg of bodyweight with no

symptoms of toxicity (this is about 8000 times the amount an

implant should produce in a day during breakin). I found figures

for gastrointestinal absorption of cobalt ranging from 5% to 30%

so this should correspond to a dose level 200-3000 times what one

would expect from an implant during breakin.

However, people aren't sheep (except metaphorically ;-) )

I also found references to adverse health effects in alcoholics who

drank a lot of beer back when they used cobalt salts to stabilize

the foam and make the head last longer. These people ingested over

40 mcg/kg bodyweight per day (that works out to 3000 micrograms/day

for someone my size - a little less than 100 times what the implant

would be expoected to throw off during breakin. Factoring in the

absorption factor range, that works out to between 5 and 30 times

the exposure one would expect from implant wear during breakin. These

individuals were alcoholics, so how much of the ill effect they

experienced was due to alcoholism and poor nutrition is open to

question, IMHO.

In any event, I wasn't comfortable making the same calculation for

cobalt, because I just didn't have the relevant information.

Hence the quite deliberate choice of title for my post.

So where did you find comparative toxicity for cobalt and chromium?

I must not have been looking in the right place.

Normal blood levels of cobalt are considerably lower than chromium,

and the amount of cobalt your body requires is much less than the

amount of chromium, but I can't find a generally accepted number for

toxicity.

> I did

> these same calcs a couple years ago and came to the same conclusion.

>

> One interesting thing is that while cobalt is a higher percentage in

> the implant alloy, the typical serum and urine ion levels of chromium

> are 50% to 2-times higher than cobalt. My guess is that cobalt is

> harder, therefore chromium is preferentially eroded in the bearing.

Or less of the cobalt is dissolving in serum, or it's being

concentrated somewhere else in the body.

>

>

> bilat C+ July 2001, metal ion study participant "

I'm *still* not worried, although I'm real glad you guys are

participating in this study. The *real* answer to this question is

going to come from your experience, not from my random scribblings on

the net.

[Guest guest]

> > One interesting thing is that while cobalt is a higher percentage

in

> > the implant alloy, the typical serum and urine ion levels of

chromium

> > are 50% to 2-times higher than cobalt. My guess is that cobalt

is

> > harder, therefore chromium is preferentially eroded in the

bearing.

>

> Or less of the cobalt is dissolving in serum, or it's being

> concentrated somewhere else in the body.

>

My understanding is that the human body is very efficient at

eliminating cobalt, more so than chromium.

-

[Guest guest]

> > > One interesting thing is that while cobalt is a higher percentage

> in

> > > the implant alloy, the typical serum and urine ion levels of

> chromium

> > > are 50% to 2-times higher than cobalt. My guess is that cobalt

> is

> > > harder, therefore chromium is preferentially eroded in the

> bearing.

> >

> > Or less of the cobalt is dissolving in serum, or it's being

> > concentrated somewhere else in the body.

> >

>

> My understanding is that the human body is very efficient at

> eliminating cobalt, more so than chromium.

>

Then why is the urine concentration lower?

If the kidneys were better at eliminating cobalt, wouldn't you

expect the serum concentration to be lower but the urine

concentration to be higher?

Steve

[Guest guest]

..

>

> I couldn't find the data to make the same calculation for cobalt.

I based my calcs on contaminant limits for tap water established

under preliminary remediation goals published by the USEPA

(google " PRGs USEPA " ). For chromium III it is about 55,000-ug/L

(based on 2-L per day) and cobalt is 3,200-ug/L.

More into on toxicology of metals is found on the CDC website.

google " cdc toxicity cobalt "

Both of these trace metals are nutrients and the trace doses that we

get are insignificant. Also, it is very likely that the actual

bioavailability of the ions created by M/M bearings is much lower as

the implants consist of zero-valent metal which has a much lower

reactivity.

Based on all of my reasearch I conclude that toxic or cancerous

effects are near zero unless you have poorly functioning kidneys.

Maybe, however, my brain is addled by all of the circulating toxic

heavy metal ions.

[Guest guest]

> .

> >

> > I couldn't find the data to make the same calculation for cobalt.

>

> I based my calcs on contaminant limits for tap water established

> under preliminary remediation goals published by the USEPA

> (google " PRGs USEPA " ). For chromium III it is about 55,000-ug/L

> (based on 2-L per day) and cobalt is 3,200-ug/L.

Yeah, but the gastrointestinal absorption factor for cobalt is

somewhere between 10 and 60 times higher than that of chromium

III (5%-30% vs.0.5%), so while the amount of cobalt ingested is

lower, much more of it is absorbed by the body.

> More into on toxicology of metals is found on the CDC website.

> google " cdc toxicity cobalt "

That's how I found that there was no chronic reference dose.

> Both of these trace metals are nutrients and the trace doses that we

> get are insignificant. Also, it is very likely that the actual

> bioavailability of the ions created by M/M bearings is much lower as

> the implants consist of zero-valent metal which has a much lower

> reactivity.

Certainly. I just based my calculation on 100% of the wear debris

oxidizing and going into the bloodstream because I wanted an absolute

worst case dosage estimate.

I think that the real dosage from the implant is probably far lower

for exactly the reason you gave. I suspect that most of the debris

consists of zero-valence metal particles which remain in the immediate

vicinity.

Anyway, as I said, the *real* clinical data on this is going to come

from people like you who are willing to put up with the inconvenience

of participating in the ion study. 10 years from now, people won't

need to make this sort of mathematical guess.

Steve

[Guest guest]

While the kidney does most of the work, the tests do not account

for the work of the liver, the waste material of which is eliminated

in bile (to the stool) rather than in the urine.

-

Re: Why chromium ions don't really worry me

(long and boring)

> > > One interesting thing is that while cobalt is a higher percentage

> in

> > > the implant alloy, the typical serum and urine ion levels of

> chromium

> > > are 50% to 2-times higher than cobalt. My guess is that cobalt

> is

> > > harder, therefore chromium is preferentially eroded in the

> bearing.

> >

> > Or less of the cobalt is dissolving in serum, or it's being

> > concentrated somewhere else in the body.

> >

>

> My understanding is that the human body is very efficient at

> eliminating cobalt, more so than chromium.

>

Then why is the urine concentration lower?

If the kidneys were better at eliminating cobalt, wouldn't you

expect the serum concentration to be lower but the urine

concentration to be higher?

Steve

[Guest guest]

> While the kidney does most of the work, the tests do not account

> for the work of the liver, the waste material of which is eliminated

> in bile (to the stool) rather than in the urine.

I don't think differences in biliary excretion can account for the low

level of cobalt relative to chromium in serum and urine.

According to the CDC Agency for Toxic Substances and Disease Registry

(http://www.atsdr.cdc.gov/HEC/CSEM/chromium/biologic_fate.html), 10%

of absorbed chromium is excreted by the biliary route.

According to the CDC toxicology profile for cobalt, only 2-7% of

an intravenous dose is excreted in bile. See

http://www.atsdr.cdc.gov/toxprofiles/tp33-c3.pdf, section 3.4.4.4,

entitled " Other Routes of Exposure " .

So, proportionally *less* cobalt is excreted in bile. This would lead

me to expect that both serum and urine levels of cobalt would still be

higher than those of chromium if the amount of each metal being

absorbed into the bloodstream was proportional to its level in the

alloy (which is mostly cobalt).

I think the difference in Co and Cr levels is therefore most probably

due to differences in:

1) oxidation rate of wear particles

2) uptake of those oxidation products into serum

3) amount of each stored elsewhere in the body

between the two metals. Just idle speculation, of course.

We should probably take this off-list before we put everyone else to

sleep.

;-)

Steve

[Guest guest]

I agree completely with your 3-item list. The metal not only has to come off

the implant but it has to become ionized and taken up into the bloodstream for

it to show up in those tests.

However, it is not necessarily true that the rates betwen two elimination paths

are constant. There are instances where one route of elimination can become

saturated and then another route can have proportionally more elimination. I'm

not at all sure that that is a factor here, but it is a possible explanation.

What I said remains true, though, Co is eliminated faster than Cr.

If you search PubMed for

cobalt disposition kidney

there is more information out there on elimination, at the moment I don't have

time to review and summarize here.

-

>

>

> Date: 2004/01/19 Mon PM 03:55:33 EST

> To: surfacehippy

> Subject: Re: Why chromium ions don't really worry me (long and

boring)

>

>

> > While the kidney does most of the work, the tests do not account

> > for the work of the liver, the waste material of which is eliminated

> > in bile (to the stool) rather than in the urine.

>

> I don't think differences in biliary excretion can account for the low

> level of cobalt relative to chromium in serum and urine.

>

> According to the CDC Agency for Toxic Substances and Disease Registry

> (http://www.atsdr.cdc.gov/HEC/CSEM/chromium/biologic_fate.html), 10%

> of absorbed chromium is excreted by the biliary route.

>

> According to the CDC toxicology profile for cobalt, only 2-7% of

> an intravenous dose is excreted in bile. See

> http://www.atsdr.cdc.gov/toxprofiles/tp33-c3.pdf, section 3.4.4.4,

> entitled " Other Routes of Exposure " .

>

> So, proportionally *less* cobalt is excreted in bile. This would lead

> me to expect that both serum and urine levels of cobalt would still be

> higher than those of chromium if the amount of each metal being

> absorbed into the bloodstream was proportional to its level in the

> alloy (which is mostly cobalt).

>

> I think the difference in Co and Cr levels is therefore most probably

> due to differences in:

>

> 1) oxidation rate of wear particles

> 2) uptake of those oxidation products into serum

> 3) amount of each stored elsewhere in the body

>

> between the two metals. Just idle speculation, of course.

>

> We should probably take this off-list before we put everyone else to

> sleep.

> ;-)

>

> Steve

[Guest guest]

I'm just dubious about differences in non-urinary excretion being enough

to account for the difference in Co and Cr serum and urine levels. I

think that there's probably also a significant difference in initial

uptake of the two metals which accounts for much of the difference in

these levels.

However, we're straying a tiny bit from my initial point:

1) Even if all the chromium wear products were oxidized to Cr(III) and

went into the bloodstream, you'd still be exposed to much less than

currently recognized " official " lifetime safe doses.

2) Even if all the cobalt wear products were oxidized and went into

the bloodstream, your absorbed dosage would be less than the EPA

will allow

you to get from your tap water, and far less than the doses

reported to cause toxicity in any animal or human studies I could

find. Since there's no chronic reference dose for cobalt, it's

not possible to make the same definitive statement about cobalt

as chromium.

Based on (1) and (2), I'm not going to fret about ion levels - but

that's a personal decision on my part. I'd love to wait for long-term

clinical studies on resurfacing patients, but I'm not willing to either:

(1) waste years of my life in agonizingly painful " watchful waiting "

(2) make the irreversible decision to get two non-MoM THRs, with all

the activity restrictions (and surgical risk from multiple

revision THRs) that this decision implies for someone my age (48)

just because of what seems to me to be a miniscule risk of ion

exposure

while waiting for the final data. If the ion studies show chronically

unacceptable levels of these substances, then I can always get the

resurfacings revised to primary THRs down the road. Conservation of

matter and simple arithmetic suggest to me that this eventuality is

pretty unlikely. Not impossible, mind you, but very, very unlikely.

ly, I think I'm far more likely to suffer adverse health

consequences from the activity restrictions of a THR and the risk of

multiple revisions than I am from ion exposure. And that doesn't even

account for quality of life differences.

To be perfectly blunt, I want my life back (to quote what seems to be

the unofficial motto of this group).

Steve

[Guest guest]

Guys,

Don’t take this off the list. I found your posts extremely informative. I

tend to go with research and facts, even when one has to put a layer of

subjective interpretation over the facts. At least the foundation is based on

facts and I can apply my own stipulations and assumptions. This is much more

valuable, to myself at least, than emotional explanations. Please, keep it up.

And thanx.

Dan Milosevic

* +44 (0)7974 981-407

* +44 (0)20 8501-2573

@ dan.milosevic@...

Re: Why chromium ions don't really worry me (long and

boring)

> While the kidney does most of the work, the tests do not account for

> the work of the liver, the waste material of which is eliminated in

> bile (to the stool) rather than in the urine.

I don't think differences in biliary excretion can account for the low level of

cobalt relative to chromium in serum and urine.

According to the CDC Agency for Toxic Substances and Disease Registry

(http://www.atsdr.cdc.gov/HEC/CSEM/chromium/biologic_fate.html), 10% of absorbed

chromium is excreted by the biliary route.

According to the CDC toxicology profile for cobalt, only 2-7% of an intravenous

dose is excreted in bile. See http://www.atsdr.cdc.gov/toxprofiles/tp33-c3.pdf,

section 3.4.4.4, entitled " Other Routes of Exposure " .

So, proportionally *less* cobalt is excreted in bile. This would lead me to

expect that both serum and urine levels of cobalt would still be higher than

those of chromium if the amount of each metal being absorbed into the

bloodstream was proportional to its level in the alloy (which is mostly cobalt).

I think the difference in Co and Cr levels is therefore most probably due to

differences in:

1) oxidation rate of wear particles

2) uptake of those oxidation products into serum

3) amount of each stored elsewhere in the body

between the two metals. Just idle speculation, of course.

We should probably take this off-list before we put everyone else to sleep.

;-)

Steve

[Guest guest]

Ditto for me.

Jude

Re: Why chromium ions don't really worry me (long and

boring)

> While the kidney does most of the work, the tests do not account for

> the work of the liver, the waste material of which is eliminated in

> bile (to the stool) rather than in the urine.

I don't think differences in biliary excretion can account for the low level of

cobalt relative to chromium in serum and urine.

According to the CDC Agency for Toxic Substances and Disease Registry

(http://www.atsdr.cdc.gov/HEC/CSEM/chromium/biologic_fate.html), 10% of absorbed

chromium is excreted by the biliary route.

According to the CDC toxicology profile for cobalt, only 2-7% of an intravenous

dose is excreted in bile. See http://www.atsdr.cdc.gov/toxprofiles/tp33-c3.pdf,

section 3.4.4.4, entitled " Other Routes of Exposure " .

So, proportionally *less* cobalt is excreted in bile. This would lead me to

expect that both serum and urine levels of cobalt would still be higher than

those of chromium if the amount of each metal being absorbed into the

bloodstream was proportional to its level in the alloy (which is mostly cobalt).

I think the difference in Co and Cr levels is therefore most probably due to

differences in:

1) oxidation rate of wear particles

2) uptake of those oxidation products into serum

3) amount of each stored elsewhere in the body

between the two metals. Just idle speculation, of course.

We should probably take this off-list before we put everyone else to sleep.

;-)

Steve

[Guest guest]

,

How do i add a photo. Thanks

Tom LBHR 6/03 DeSmet