Chromium trioxide

Endpoint summary

Description of key information

Proprietary (guideline & GLP-compliant) acute oral, dermal and inhalation studies are available for the compounds in this group. A number of additional published studies have been reviewed by the UK Health & Safety Executive (HSE, 1989), the UK Institute of Occupational Health (IOH, 1997) and the EU RAR (2005). The EU RAR also covers the studies previously reviewed in the other two reports.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited reporting (study summary only) of a guideline-comparable study.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not reported

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

No further details reported

Doses:

0, 32, 40, 50, 63, 80 & 100 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

52 mg/kg bw

95% CL:

>= 42 - <= 62

Mortality:

Deaths occurred at 32 mg/kg bw (1M, 2F), 40 mg/kg bw (1M), 50 mg/kg bw (2M, 3F), 63 mg/kg bw (3M, 4F), 80 mg/kg bw (3M, 4F) and 100 mg/kg bw (5M, 5F), within three days of dosing.

Clinical signs:

other: Lacrimation, hunched posture, hypoactivity, soft/reduced faeces, anogenital staining, red/brown facial staining.

Gross pathology:

Findings were apparent in the stomach, intestines, brain, kidney and lungs in decedent animals in all groups, but may have been secondary effects. No effects of treatment were apparent in animals surviving to scheduled necropsy.

Other findings:

Slightly increased liver weights

The report indicates that the primary cause of death was gastrointestinal corrosion, rather than systemic toxicity.

Interpretation of results:

other: Toxic if swallowed based on EU GHS criteria

Conclusions:

The acute oral LD50 of chromic acid was found to be 52 (42-62) mg/kg bw in the rat. Chromic acid is classified as 'Toxic if swallowed', based on the results of this study.

Executive summary:

Fischer 344 rats (5/sex/group) were gavaged with a single dose of chromic acid at dose levels of 0, 32, 40, 50, 63, 80 or 100 mg/kg bw and observed for 14 days. Deaths occurred in all dose groups, within 3 days of dosing. Reduced weight gain or initial weight loss was apparent in all groups. Gross necropsy of decedents revealed corrosive effects on the gastrointestinal tract. The acute oral LD50 of chromic acid in the rat was found to be 52 (42-62) mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

52 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Full, guideline and GLP-compliant study report.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1150 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, NC, USA
- Age at study initiation: 9-16 weeks
- Weight at study initiation: 194-271 g (males); 147-170 g (females)
- Fasting period before study: Not stated
- Housing: Individual
- Diet: ad libitum
- Water: ad libitum (automated)
- Acclimation period: 15-55 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67-79
- Humidity (%): 40-70
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 14/1/88 To: 7/3/88

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

water

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 100 l
- Method of holding animals in test chamber: individual wire mesh cages
- Source and rate of air: compressed air: 20 litres/minute
- System of generating particulates/aerosols: nebuliser
- Method of particle size determination: cascade impactor
- Temperature, humidity, pressure in air chamber: Temperature 69-76F; humidity 48-100%


TEST ATMOSPHERE
- Brief description of analytical method used: colorimetric
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable): water
- Concentration of test material in vehicle (if applicable): 2.5-40%
- Justification of choice of vehicle: solubility & toxicologically inter
- Lot/batch no. (if required): -
- Purity: -


TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.5-3.2 microns (gsd 1.8-1.98 microns); 92% <10 microns

Analytical verification of test atmosphere concentrations:

yes

Remarks:

colorimetric assay

Duration of exposure:

4 h

Concentrations:

0, 190, 300, 330, 420 and 2200 mg/m3 (mean analytical concentration)

No. of animals per sex per dose:

5/sex

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at frequent intervals on the day of exposure and daily thereafter
- Necropsy of survivors performed: yes/no
- Other examinations performed: detailed physical observations; bodyweight (Days -1, 1, 1, 3, 5, 8, 15); gross necropsy; organ weights (brain, heart, kidneys, liver, lungs, ovaroes, spleen and testes).

Statistics:

Litchfield and Wilcoxon (1949): calculation of LC50

Sex:

female

Dose descriptor:

LC50

Effect level:

167 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

>= 116 - <= 238

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

263 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

>= 224 - <= 309

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

217 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

>= 188 - <= 251

Exp. duration:

4 h

Mortality:

Deaths occurred at 190 mg/l (3F); 300 mg/m3 (1F); 330 mg/m3 (5M, 5F); 420 mg/m3 (5M, 5F) and 2200 mg/m3 (5M, 5F).

Clinical signs:

other: Hypoactivity, closed eyes, lacrimation and salivation were observed during exposure. Nasal discharge, salivation and anogenital staining were observed after expousre, with laboured/noisy breathing also reported at 330 and 420 mg/m3.

Body weight:

Significant weight losses were seen following exposure; surviving animals gained weight during the second study week.

Gross pathology:

Discoloured lungs and nasal turbinates were observed in decedent animals.

Other findings:

Lung weights and kidney weights were slightly higher in survivors at 190 and 300 mg/m3.

Signs of toxicity (secretory responses, hypoactivity and closed eyes) were observed during the exposure period. Similar signs and noisy/laboured breathing were also noted following exposure. Weight loss was seen following exposure, with some recovery apparent in surviving animals. Gross necropsy of decedents showed discolored lungs and nasal turbinates: increased lung and kidney weights were also seen. Findings indicate pulmonary irritation to be a cause of death within 1 -2 days of exposure; renal failure is postulated to be a cause of delayed mortality.

Concentration (mg/m3)	Mortality			Particle size
	M	F	M+F	MMAD (um)	gsd	10 uM
0	-	-	-	-	-	-
190	-	3	3	3.2	1.8	97%
300	-	1	1	2.9	1.8	99%
330	5	5	10	2.5	1.8	99%
420	5	5	10	3.1	1.9	97%
2200	5	5	10	2.8	1.8	99%

Conclusions:

The acute LC50 of chromic acid was calculated to be 263 (224 -309) mg/m3 in males, 167 (116 -238) mg/m3 in females and 217 (188 -251) mg/m3 in the sexes combined.

Executive summary:

F344 rats (5/sex/group) were exposed (whole body) for 4 hours to liquid aerosols of chromic acid (in water). Deaths occurred in all exposed groups during or immediately following exposure to the highest concentration or between Days 2 -10 at the lower concentrations. Signs of toxicity (secretory responses, hypoactivity and closed eyes) were observed during the exposure period. Similar signs and noisy/laboured breathing were also noted following exposure. Weight loss was seen following exposure, with some recovery apparent in surviving animals. Gross necropsy of decedents showed discolored lungs and nasal turbinates: increased lung and kidney weights were also seen. Findings indicate pulmonary irritation to be a cause of death within 1 -2 days of exposure; renal failure is postulated to be a cause of delayed mortality.

The acute LC50 of chromic acid was calculated to be 263 (224 -309) mg/m³ in males, 167 (116 -238) mg/m³ in females and 217 (188 -251) mg/m³ in the sexes combined.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

217 mg/m³ air

Physical form:

inhalation: aerosol

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17/09/1987 - 21/04/1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

Chromic acid was administered for 24 hours to the shorn dorsal skin of New Zealand White Rabbits (10/dose level) at 0, 35, 55, 80, 110 or 160 mg/kg bw. Animals were observed for 14 days; bodyweights were recorded weekly. Organ weights were recorded at necrospy.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: King's Wheel Rabbitry, Mount Vernon, Ohio
- Fasting period before study: not specified
- Housing: animals were housed individually in suspended stainless steel cages
- Diet (e.g. ad libitum): animals received Purina® Rabbit Chow HF® (Number 5326), feed was available ad libitum during acclimation and throughout the study
- Water (e.g. ad libitum): Tap water (supplied by the City of Painesville) was available ad libitum through an automatic watering system or water bottles during the acclimation periods and an automatic watering system during the study period
- Acclimation period: animals were housed for a minimun fourteen day acclimation period prior to study initiation
- Method of randomisation in assigning animals to test and control groups: The animals were assigned to the study by a computer-generated random process.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 62° to 70° (A temperature greater than 70°F (73°F) vas recorded once during the acclimation period)
- Humidity (%): 40 to 70% (Relative humidities less than 40% (32 and 34%) were recorded on two days during the acclimation and study periods)
- Air changes (per hr): air flow in the room was equal to eleven or more fresh air changes per hour
- Photoperiod (hrs dark / hrs light): twelve hour light/dark cycle

IN-LIFE DATES: From: February 12, 1988 (animal receipt) To: March 17, 1988 (termination)

Type of coverage:

occlusive

Vehicle:

physiological saline

Remarks:

The material was moistened with physiological saline at the time of application to the animal

Details on dermal exposure:

Approximately 24 hours prior to dermal application of the test material, the back and sides of each of the selected rabbits were clipped free of hair with electric clippers. Care was taken to avoid abrading the skin during the clipping of the backs. The dorsal epidermis of each of the animals was considered healthy and suitable for the purpose of the study. For the main study, each animal was identified permanently with an ear tag, imprinted with a unique number, and by cage card. The animals were returned to their cages to await testing on the following day.

For each of the treated groups in the main study, the volume of saline applied to moisten the test material was equivalent to two times the amount of administered test material. A group of control animals received the vehicle (saline) by topical application at a volume equivalent to the dosage of saline administered to animals at the 160 mg/kg level, the highest level tested.
The patch was applied to the site on the back of the rabbit and secured in place with the Blenderm® tape backing. Plastic sheeting (Saran Wrap™, cut approximately 12 inches in length and folded lengthwise in half) was wrapped around the trunk of the animal, covering the patch and tape. To further secure the patch and sheeting, the trunk of the animal was wrapped with elastic Vetrap® which vas secured at either side with 2 inch Blenderm® tape. A plastic restraining collar was placed around the rabbit's neck and the animal was returned to the cage. These procedures were repeated for each animal.
After a twenty-four hour exposure period, the bandaging and patch and the restraining collar were removed from each rabbit. After the removal of each patch, the skin of each back was gently rinsed and wiped, using tap water and disposable paper towels to aid in the removal of any remaining test material.

Duration of exposure:

24 hours

Doses:

0, 35, 55, 80, 110 and 160 mg/kg bw.

No. of animals per sex per dose:

Five animals per sex per dose (expect for 35 mg/kg group: Upon necropsy at the termination of the study, one of the animals assigned to the male group at the 35 mg/kg dose level was found to be a female. Therefore, the 35 mg/kg group consisted of four male and six female rabbits during this study)

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Days -7, -1, 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
The gross necropsy included but was not limited to the following examinations:
External: included inspection and palpation of the rabbit, and examination of all external orifices and skin at the exposure site.
Internal: included examination of the tissues in the neck, all major viscera and body cavities. Care was taken to examine the exterior surfaces of the brain and the lining of the cranial cavity as well as the serosal surfaces lining the thoracic, abdominal and pelvic cavities.
The stomach was opened along the greater curvature and the mucosal surface was examined. An eight to ten centimeter segment of the duodenum (nearest to the stomach), jejunum, ileum (nearest to the cecum) and descending colon was opened and was examined.
Tissues considered abnormal were retained in 10% neutral buffered formalin. No histopathology was scheduled.
Organ Weights: For animals surviving to termination (day 14) of the study, the following organs were weighed: brain, heart, lungs with trachea (severed just below the larynx), liver, spleen, each kidney, testes or ovaries.

Statistics:

The acute dermal LD50 with 95% confidence limits (as applicable) was calculated from the mortality data by the probit analysis method of D. J. Finney, Probit Analysis, Cambridge University Press, 1971, for males and females separately and also for the combined sexes. The slope of each dose response curve was calculated and presented as applicable.

Preliminary study:

Groups of one male and one female rabbit were assigned to each of the following dose groups: 32, 50, 80, 125, 200, 320, 500, 2000 mg/kg. The rabbits were observed for viability at three intervals on the day of dosing and once or twice daily thereafter for at least 7 days. During the viability observations, significant clinical findings were recorded.
The animals in the 200, 320, 500 and 2000 mg/kg groups were found dead within 24 hours of the dose administration. The animals in the 125 mg/kg group were found dead by day 7 following dose administration. Except for mortality, no significant clinical findings were noted in animals in any of the dose groups during the range-finding study. The individual body weights on the day of dose administration ranged from 2450 to 2700 g for male rabbits and from 2300 to 2600 g for female rabbits.
Gross pathologic findings noted externally in animals during the range-finding study included anogenital staining in the 125 to 2000 mg/kg groups and numerous dermal effects at the site of application in each of the groups. The dermal effects included yellow brown staining, hardened and leather-like texture of the skin, thickened skin, sloughing and necrosis. Findings observed internally consisted of pale, mottled and/or swollen kidneys, red foci on the kidneys, a mottled liver and black foci on the luminal surface of the stomach.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

57 mg/kg bw

Based on:

test mat.

95% CL:

>= 47 - <= 66

Mortality:

Deaths occurred at 55 mg/kg bw (3M, 2F); 80 mg/kg bw (5M, 4F); 110 mg/kg bw (5M, 5F) and 160 mg/kg bw (5M, 4F)
Deaths occurred between Days 1-12: The animals which died in the 160 mg/kg group were found dead by day 3 of the study. The animals in the 110 mg/kg group were found dead by day 6. With the exception of one animal in the 80 mg/kg group which was found dead on day 12, the animals which died in the 55 and 80 mg/kg groups were found dead by day 8 of the study

Clinical signs:

other: Signs of systemic toxicity included anogenital staining, nasal discharge, anorexia, hypothermia and prostration. Local findings at the application site included oedema (at early time points), severe erythema and eschar formation. Skin at the application s

Gross pathology:

External findings, noted in rabbits in each of the treated groups were yellow-brown staining of the fur and skin at the application site and areas of dried, thickened, leather-like skin at the application site. Edema and black and/or gray foci were noted at the site of application in animals in the 55 through 160 mg/kg groups. Anogenital staining also was noted in animals in these groups.
Findings observed internally at necropsy in the 55, 80, 110 and 160 mg/kg dose groups were pale and enlarged kidneys and colored (e.g., brown, black or red) foci in the stomach muscosa. Pale kidneys also were observed in the 35 mg/kg group. Yellow discoloration and/or accentuated lobulation of the liver were observed in the 80, 110 and 160 mg/kg groups. These findings were considered treatment related.
No pathologic findings were noted externally in any of the control rabbits. Pathologic findings observed internally in the control animals included multiple red foci on the lungs of one animal, red discoloration of a mandibular lymph node in another animal and a small ovary in a third rabbit.

Other findings:

Potential target organs: kidney
Evaluation of organ weight data showed a possible effect on kidney weights in male and female rabbits. Increases in the mean kidney weights were observed in each of the treated groups when compared with the control group. Increases in kidney weight relative to body and brain weights also were noted in the treated groups when compared with controls. The individual kidney weights of most surviving males and females in the treated groups exceeded the highest individual weights in the control animals.
A possible effect on liver weight was noted only in the one surviving female rabbit in the high dose group. The absolute liver weight and the liver weight relative to brain weight for this animal was less than the liver weights for many females in the other groups. The liver weight relative to body weight for this animal was within the range of control female weights. Interpretation of the significance of the lower liver weight is difficult because there was only one surviving animal in the high dose group.
Organ weight data for each of the other organs in the treated groups were considered similar to control weights.

The acute dermal LD50 of chromic aicd in the rabbit was found to be 57 mg/kg bw.

Interpretation of results:

other: Toxic in contact with skin based on EU GHS criteria

Conclusions:

The acute dermal LD50 of chromic acid was found to be 57 mg/kg bw.

Executive summary:

Chromic acid was applied for 24 hours under occlusive conditions to the shorn dorsal skin of New Zealand Whire rabbits (5/sex) at dose levels of 0, 35, 55, 80, 110 or 180 mg/kg bw. Animals were observed for 14 days.

Deaths occurred at dose levels of 55 mg/kg bw/d and greater. Signs of systemic toxicity and local dermal irritation at the application site were observed.

The acute dermal LD50 of chromic acid was found to be 57 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

57 mg/kg bw

Additional information

Studies show that chromium trioxide is acutely toxic by the oral and dermal routes and is very toxic by inhalation. The primary effects of exposure appear to be corrosion at the site of exposure, however evidence of renal toxicity was also seen in the dermal and inhalation toxicity studies. The acute oral toxicity of chromium trioxide is slightly higher than that of other water-soluble hexavalent chromium compounds, possibly as a consequence of more severe local corrosive effects due to the low pH of this substance. The acute inhalation toxicity is comparable to that of other water-soluble hexavalent chromium compounds, however the acute dermal toxicity of chromium trioxide is much more severe due to local effects.

Acute oral toxicity

The results of proprietary acute oral toxicity studies (Loser, 1987; Shults, 1987) are consistent with the results of other studies available in the literature (EU RAR, 2005) and report the lowest acute oral LD50 values (of 52 and 80 mg/kg bw/d respectively) for chromium trioxide. The UK IOH review (1997) also reports the results of a study with chromium trioxide (Kobayashi et al, 1976) which gives acute oral LD50 values of 41 -59 mg Cr /kg bw, which would appear to be broadly consistent with the results of other studies.

The acute oral LD50 of sodium chromate, sodium dichromate and potassium dichromate in the rat was found to be 129.5 mg/kg bw (males) and 67.0 mg/kg bw (females), 123.5 mg/kg bw (males) and 86.5 mg/kg bw (females), and 168.0 mg/kg bw (males) and 90.5 mg/kg bw (females), respectively in a proprietary, guideline-compliant study (Cuthbert & D'Arcy-Burt, 1983). Findings are consistent with those reported in the literature (EU RAR, 2005; UK IOH, 1997) and in an additional guideline-compliant study (Gad et al, 1985) which reported values of 67.08 (males) and 40.57 mg/kg bw (females), 56.64 (males) and 39.02 mg/kg bw (females), and 74.11 (males) and 47.94 mg/kg bw (females) for sodium chromate, sodium dichromate and potassium dichromate respectively.

Overall, as assessed in the EU RAR, the available data on oral toxicity indicate greater sensitivity of the rat compared to the mouse, and greater sensitivity of males compared to females. Findings indicate that corrosion of the gastrointestinal tract may be the critical toxic effect.

Acute inhalation toxicity

The only available acute inhalation toxicity for chromium trioxide is the proprietary study (Rhinehart, 1989), which reports an LC50 value of 217 mg/m3. The results of this study indicate local irritation/corrosion of the respiratory tract to be the primary cause of immediate death, with some evidence also for delayed mortality due to renal toxicity.

A proprietary study (Greenough & McDonald) reported 100% mortality for sodium chromate, sodium dichromate and potassium dichromate at a concentration of 3.15 mg/L, 2.1 mg/L and 1.72 mg/L, respectively. A guideline-comparable study (Hoffman, 1985) with potassium dichromate reported LC50 values of 99 and 83 mg/m3 in males and female rats respectively.

The results of an additional study (Gad et al, 1986) reported briefly in the UK IOH review (1997) reports an LC50 value of 104 mg/m3, 200 mg/m3, and 99 mg/m3 for sodium chromate, sodium dichromate and potassium dichromate, respectively.

Acute dermal toxicity

The results of the proprietary acute dermal toxicity study (Shults, 1987) are also discussed in the EU RAR, and in fact are the only data available for this compound. In comparison to the other Cr (VI) compounds, chromium trioxide was found to be of relatively high acute dermal toxicity (LD50 = 57 mg/kg bw). This finding is considered highly likley to be a consequence of the severity of the local dermal effects seen following exposure to this corrosive chemical. It is notable that mortality was also seen in a dermal irritation screening study in rabbits performed with chromium trioxide (Thyssen, 1979) at dose levels equivalent to 125 -170 mg/kg bw.

The acute dermal LD50 of sodium chromate, sodium dichromate and potassium dichromate was found to be >2000 mg/kg bw in a guideline-compliant study in the rabbit (Cuthbert & D'Arcy-Burt, 1983). The findings of this study contrast with the results of an additional guideline-compliant study (Gad et al, 1986) using the same application conditions, in which a dermal LD50 of 1330 mg/kg bw, 960 mg/kg bw, and 1860 mg/kg bw was determined in male rabbits for sodium chromate, sodium dichromate and potassium dichromate, respectively. Signs of systemic toxicity were noted in a skin irritation study in the rabbit (Cuthbert & D'Arcy-Burt, 1982); the level of mortality in this study indicates a dermal LD50 of or <250 mg/kg bw for sodium chromate or dichromate, however findings may be due to the use of a vehicle in this study which increased the bioavailability of the test substance.

Overall, as assessed in the EU RAR, the water soluble Cr (VI) compounds sodium chromate, sodium dichromate and potassium dichromate are of moderate acute dermal toxicity in the rat and are of comparable toxicity to each other. Chromium trioxide is of greater acute dermal toxicity in the rat than the other compounds; this finding is likely to be due to the severity of the local effects following dermal exposure to this corrosive compound.

In addition, a number of studies are reported in which the toxicity of hexavalent chromium compounds (potassium dichromate, sodium chromate or potassium chromate) was assessed in rats by (single dose) intraperitoneal or subcutaneous administration. Effects indicative of renal toxicity (altered urinary protein or enzyme levels, histopathology of the proximal tubular epithelium) were reported in these studies.

Taken together, acute administration of low doses of Cr (VI) compounds by parenteral (subcutaneous or intraperitoneal) injection to rats was found to cause kidney toxicity. These findings are therefore consistent with the known effects of Cr (VI) toxicity and do not raise any additional concerns. The relatively low dose levels resulting in toxicity in these studies compared to those seen following oral and dermal dosing reflects the relatively poor bioavailability of Cr (VI) compounds by these routes of exposure.

Justification for classification or non-classification

Chromium (VI) trioxide is listed in Annex VI to Regulation (EC) No 1272/2008 under Index No 024-001-00-0 with the following harmonised classification:

Acute Tox 2, H330 'Fatal if inhaled'

Acute Tox 3, H311 'Toxic in contact with skin'

Acute Tox 3, H301 'Toxic if swallowed'

This classification is consistent with the data available in the literature and reviewed in the EU RAR. No change to this classification is proposed.