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Clinical Toxicology, 37(2), 195200 (1999)

Therapeutic Review: Is Ascorbic Acid

of Value in Chromium Poisoning
and Chromium Dermatitis?
Sally M. Bradberry; J. Allister Vale
National Poisons Information Service (Birmingham Centre), City Hospital,
Birmingham, United Kingdom

ABSTRACT
Introduction: Repeated topical exposure to chromium(VI) may cause an allergic contact dermatitis or the formation of chrome ulcers. Systemic toxicity may
occur following the ingestion of a chromium(VI) salt, from chromium(VI)-induced skin burns, or from inhalation of chromium(VI) occurring occupationally. Soluble chromium(VI) salts are usually absorbed more easily and cross
cell membranes more readily than trivalent chromium salts, and, therefore
chromium(VI) is more toxic than chromium(III). In experimental studies, endogenous ascorbic acid in rat lung, liver, and kidney and human plasma, effectively reduces chromium(VI) to chromium(III). The administration of exogenous ascorbic acid has been advocated therefore in the treatment of systemic
chromium poisoning and chromium dermatitis to enhance the extracellular reduction of chromium(VI) to the less bioavailable chromium(III). Review: In
vitro experiments confirm that the addition of ascorbic acid to plasma containing chromium(VI) leads to a dose-dependent reduction of chromium(VI)
to chromium(III). In animal studies, parenteral ascorbic acid 0.55 g/kg significantly reduced chromium-induced nephrotoxicity when administered 30
minutes before parenteral sodium dichromate and up to 1 hour after parenteral
sodium chromate dosing. Parenteral ascorbic acid 0.55 g/kg also reduced mortality when given orally up to 2 hours after oral potassium dichromate dosing.
However, the administration of parenteral ascorbic acid more than 2 hours
after parenteral chromate in these experimental studies did not protect against

Correspondence: Dr. J. Allister Vale, National Poisons Information Service (Birmingham Centre), West Midlands Poisons Unit, City
Hospital NHS Trust, Birmingham, B18 7QH, UK. Tel: 121 507 5588. Fax: 121 507 5580.
195
Copyright 1999 by Marcel Dekker, Inc.

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Bradberry and Vale

renal damage, and parenteral ascorbic acid given 3 hours postparenteral chromate increased toxicity. In addition, there is no confirmed clinical evidence that
the administration of ascorbic acid lessens morbidity or mortality in systemic
chromium poisoning. A possible reason for the lack of benefit of ascorbic acid
when administration is delayed, is that chromium(VI) cellular uptake has occurred prior to ascorbic acid administration. Topical 10% ascorbic acid has
been claimed to reduce significantly the healing time of experimentally induced
chrome ulcers in guinea pigs. The proposed mechanism is reduction on the skin
surface of chromium(VI) to chromium(III). Several case reports suggest that
topical ascorbic acid is effective in the management of chromium dermatitis
but this has not been confirmed in controlled clinical trials and, moreover, the
practical difficulties of frequent application are likely to limit its usefulness.
Discussion: Based on experimental studies, substantial amounts of ascorbic acid
would need to be administered, preferably parenterally, soon after exposure
to prevent systemic toxicity from chromium(VI) in humans. However, as
ascorbic acid is a metabolic precursor of oxalate, the administration of ascorbic
acid in high dose could lead to acute oxalate nephropathy, particularly in the
presence of renal failure. While smaller doses of ascorbic acid (e.g., 10 g intravenously) are not toxic, such doses probably will not reduce the mortality from
systemic chromium poisoning. Conclusion: There is currently insufficient evidence to advocate the use of ascorbic acid in the management of systemic chromium toxicity. Topical ascorbic acid may reduce dermal hexavalent chromium
exposure, but this observation must be confirmed in controlled studies.

INTRODUCTION
Chromium toxicity is caused primarily by soluble
chromium(VI) salts which are absorbed more easily 1 and
cross cell membranes more readily 2 than chromium(III).
The extracellular reduction of chromium(VI) to chromium(III) can serve as a defense mechanism against chromium(VI) toxicity. However, once absorbed, the cytotoxic and genotoxic effects of chromium(VI) are
mediated by intermediates formed during the intracellular reduction of chromium(VI) to chromium(III).35
Acute topical exposure to chromic acid or hot chromate solutions typically produces burns, and systemic
chromium absorption may occur causing renal or hepatic
failure.6 When ingested, chromium(VI) causes gastrointestinal hemorrhage and shock which may precipitate
multi-organ failure and death.7,8 Chronic topical chromium(VI) exposure characteristically leads to the formation
of chrome ulcers, independent of chromium sensitivity.9
Chromium(VI) salts also are an important cause of contact dermatitis.10,11 Although topical chromium(III) is a
weak sensitizer,12 intracutaneous chromium(III) administration often will initiate an allergic response in chromium-sensitive individuals.
It has been recommended that ascorbic acid should
be administered to patients with chromium poisoning to
reduce systemic toxicity 13,14 and that ascorbic acid should

be applied locally as a barrier cream to prevent chromium

dermatitis.15 Moreover, some chromium manufacturers
recommend the use of ascorbic acid both topically and
systemically in chromium poisoning.16 Are these recommendations valid?
ASCORBIC ACID IN SYSTEMIC
CHROMIUM TOXICITY
The role of oral and parenteral ascorbic acid in systemic chromium toxicity has been investigated experimentally and clinically.
In Vitro Studies
In vitro experiments confirm that endogenous ascorbic
acid contributes to the reduction of chromium(VI) in rat
liver, kidney,17 lung,18,19 and human plasma 14 and that the
capacity of human plasma to reduce chromium(VI) can
be enhanced in a dose-dependent manner by the prior
addition of ascorbic acid.14 Jakobsen and Eik-Nes 20 demonstrated that the viability of a cultured human cell line
was reduced significantly by the addition of potassium
dichromate (8 107 M) but that the concomitant addition of ascorbic acid (5.7 105 M) and dichromate resulted in no significant cell loss.

Ascorbic Acid in Chromium Poisoning

197

Table 1

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Effect of Oral Ascorbic Acid 800 mg on Rats Fed

25 mg Chromium(VI) [after Samitz et al.13]
n

Time (h) of Ascorbic Acid

Administration

% Mortality

8
8
6
7
7
6

Control
0
0.5
1.0
2.0
3.0

100
100
0
14
14
100

Animal Studies
Several workers have investigated the role of ascorbic
acid in the treatment of chromium poisoned animals.
Samitz et al. 13 reported that the oral administration of
ascorbic acid 800 mg either concomitant with, or 30 minutes after, 25 mg oral chromium(VI) as potassium dichromate, completely protected rats against chromium-induced mortality (Table 1). When ascorbic acid was
administered at 1 or 2 hours after chromium dosing, 86%
of rats survived but this benefit was lost completely when
the administration of ascorbic acid was delayed for 3
hours (Table 1).
Na et al.21 investigated the effect of ascorbic acid on
chromium-induced nephrotoxicity in rats (n 57).
Ascorbic acid 500 mg/kg intraperitoneally reduced significantly chromium-induced nephrotoxicity (p 0.01),
measured as an elevation of blood urea nitrogen, when
administered to rats 30 minutes before sodium dichromate 20 mg/kg subcutaneously. This protection was lost

if the administration of ascorbic acid was delayed for 2

or more hours after chromate dosing. Appenroth et al.22
found that chromate-induced proteinuria in rats (n
6) could be prevented by the concomitant administration of sodium chromate 10 mg/kg subcutaneously and
ascorbic acid 5 g/kg intraperitoneally. A significant reduction in proteinuria (p 0.05) occurred when ascorbic
acid was given up to 1 hour after chromate dosing (Table 2).
In order to investigate whether the beneficial effect
of ascorbic acid on chromate-induced nephrotoxicity was
due to reduced renal chromium uptake, Appenroth et al.22
considered the effect of ascorbic acid on the renal chromium concentration 24 hours after chromate dosing.
They found that only the instantaneous administration of
ascorbic acid and dichromate led to a reduction in renal
chromium uptake (p 0.05), even though their previous
study 22 had shown a reduction in chromium-induced
nephrotoxicity when ascorbic acid was administered up
to 1 hour after chromate dosing. The authors suggested
that whereas concomitant administration of ascorbic acid
and chromate led to the rapid reduction of chromium(VI)
to chromium(III) in the blood (with enhanced renal chromium(III) clearance and reduced renal chromium deposition), ascorbic acid given 1 hour after chromate dosing
might protect against chromium-induced proteinuria by
acting as a scavenger of toxic free radicals produced by
absorbed chromium(VI) rather than by reducing the
chromium concentration in renal tissue. Interestingly,
these workers found that the administration of ascorbic
acid 3 hours postchromate dosing enhanced nephrotoxicity (Table 2) and suggested that this might be due to the
increased generation of toxic activated oxygen species
during accelerated intracellular chromium(VI) reduction.

Table 2
Effect of Ascorbic Acid 5g/kg Intraperitoneally on Sodium Chromate 10 mg/kg Subcutaneously Induced
Nephrotoxicity in Rats [after Appenroth et al.22]
Mean SEM Urine Protein Excretion (mg/kg/h)
24 h After Chromate Administration

Time (h) of Ascorbic

Acid Administration
Control (no chromate)
Sodium chromate alone
0
0.5
1.0
3.0
* p 0.05

1.1
8.7
1.7
2.3
5.8
12.2

0.4
0.7
0.6
0.4
0.8
1.2

*
*

*
*

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Bradberry and Vale

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Case Reports
Table 3 summarizes the published case reports. These
studies provide no strong evidence that the systemic administration of ascorbic acid lessens morbidity or mortality in severe chromium poisoning, although based on animal studies the doses of ascorbic acid administered were
sub-optimal.
A 22-month-old child died 2 days after ingesting ammonium dichromate 1 g, despite a continuous ascorbic
acid infusion 10 mg/kg/h initiated within the first hour.7
Korallus et al.14 reported a favorable course in a man
with extensive chromic acid burns who was given intravenous ascorbic acid 1 g within a few minutes of the
accident and a further 1 g 40 minutes later. In a further
report,6 a 49-year-old male died from extensive chromic
acid burns despite intensive supportive treatment and the
administration of ascorbic acid 5 g daily from the day of
injury until death.
A 19-year-old man who fell into a vat of chromic acid
sustained second- and third-degree burns, gastrointestinal
ulceration, and acute renal failure.25 He received ascorbic
acid 100 mg 3 times/d (route and duration not stated)
from day 1 in addition to peritoneal dialysis (commenced
day 4). He survived with recovery of renal function over
35 days.
Walpole et al.23 reported a 2-year-old who presented
with vomiting 1 hour after supposedly ingesting sodium
dichromate. The child received ascorbic acid 1 g orally 2

hours postexposure and then daily. The plasma creatinine

concentrations were not cited but the authors stated that
urine output at no time diminished.
A 14-year-old boy died 11 days after deliberately ingesting potassium dichromate 1.5 g to get high.24 He
became anuric at 24 hours and received ascorbic acid
0.3 g daily (route of administration not stated) from day
3 until death.
TOPICAL ASCORBIC ACID FOR
CHROME ULCERS AND CHROMIUM
DERMATITIS
Experimental Studies
Pirozzi et al.29 investigated the effect, in guinea pigs,
of topical ascorbic acid on the healing time of superficial
skin abrasions to which potassium dichromate 1 mL (0.34
M) had been applied. The immediate application of potassium dichromate increased the mean healing time as
judged by the absence of crust or ulcer on the abrasions (n 1012) from 5.3 to 15.1 days (Table 4).
In a separate experiment, 7 animals received 4 potassium dichromate treated abrasions each, to which a
wash solution of 10% ascorbic acid was applied immediately or 5, 15, or 30 minutes after dichromate. The
mean healing times were 5.9, 7.3, 7.4, and 9.0 days, respectively (Table 4).
In a further experiment, the authors reported a mean

Table 3
Ascorbic Acid in Chromium Poisoning: Clinical Studies
Ascorbic Acid Administration
Age
(Y)

Nature of
Poisoning

Dose
g/d

Dichromate
ingestion
Dichromate
ingestion
Dichromate
ingestion
Chromic acid
burns
Chromic acid
burns
Chromic acid
burns

14
1.8
39
49
19

ARFAcute renal failure.

Route

Time PostExposure

ARF

1.0
?duration
0.3

Oral

2.0 h

no

survived

23

3.0 d

yes

died (day 8)

24

2.4

IV

0.5 h

yes

died (day 2)

2
(day 1)
5

IV

1h

no

survived

day 1

yes

died (day 6)

0.3

day 2

yes

survived

Outcome

Ref.

14
6
25

Ascorbic Acid in Chromium Poisoning

199

Table 4

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The Effect of Ascorbic Acid 10% on Potassium Dichromate (0.34M)-Induced Ulcers in Guinea Pigs
[After Pirozzi et al.28]
Time (mean SD days)
Required for Healing

Time (min) of Ascorbic Acid Application

12
10
8

Control (skin abrasion only)

Control (abrasion potassium dichromate)
Control abrasion potassium dichromate immediately washed
with water only
0
5
15
30

7
7
7
7

healing time of 13.5 days for potassium dichromatetreated abrasions (n 8) washed immediately with water
only, suggesting that wound irrigation alone was insufficient to reduce healing time (Table 4). The authors concluded that a 10% solution of ascorbic acid will accelerate the healing of experimentally induced chrome ulcers
and that the interval between exposure to the potassium
dichromate and application of ascorbic acid solutions is
an important factor in the degree of protection offered.
However, bias may have been introduced because there
is no evidence that the observer was blinded to treatments
received. Moreover, it is much more likely that the apparently hastened healing reflected prevention of hexavalent
chromium penetration of the abrasion (via hexavalent to
trivalent chromium reduction) rather than treatment
of a hexavalent chromium-induced lesion.
Few clinical data have been reported regarding the use
of topical ascorbic acid in the prevention of the dermatological effects of chronic occupational hexavalent chromium exposure. Table 5 summarizes the findings from 3
papers involving the regular application (at least 3 times
during the working day) of ascorbic acid 10% in solution
or as an ointment in 7 workers with established chromium

5.3 1.1
15.1 2.8
13.5 3.9
5.9
7.3
7.4
9.0

0.9
2.6
2.1
2.8

dermatitis. Resolution of dermatitis was observed in 5

patients. This again most likely reflects a decrease in reexposure rather than treatment per se.

DISCUSSION
Based on experimental studies, substantial amounts of
ascorbic acid would need to be administered, preferably
parenterally, soon after chromium exposure to prevent
toxicity. However, since ascorbic acid is a metabolic precursor of oxalate, it is known that high doses of ascorbic
acid can lead to hyperoxaluria,26 acute oxalate nephropathy,27 and permanent renal failure, particularly in patients
with pre-existing renal impairment. 28 These clinical observations may partially explain the experimental observation22 that chromate-induced nephrotoxicity may be enhanced by delay in ascorbic acid administration. Smaller
doses of ascorbic acid (e.g., 10 g), although non-toxic,
probably will not reduce the mortality from systemic
chromium poisoning, although controlled clinical studies
have not yet been performed.

Table 5
Role of Ascorbic Acid 10% in the Prevention of Chromium Dermatitis
% Resolution of
Dermatitis
Occupation

Administration of Ascorbic Acid

Lithographer
Printer
Radiologist

5
1
1

Washing in solution as required

Hourly washing in solution
Ointment 3 times daily

Complete

Partial

Ref.

60
100
100

40

30
15
31

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CONCLUSIONS
In vitro and animal studies indicate that ascorbic acid
administered in large doses is most likely to be effective
if administered immediately after exposure. There is no
clinical evidence that delayed administration of ascorbic
acid improves the prognosis of patients with severe chromium poisoning. On the contrary, animal studies demonstrate that if ascorbic acid is administered 3 hours after
exposure, it may even increase morbidity and mortality.
Case reports suggest topical ascorbic acid is effective in
the prevention of chromium dermatitis, but this has not
been confirmed in controlled clinical trials and, moreover, the practical difficulties of frequent application are
likely to limit its usefulness.

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