Chromium trioxide

Acute Toxicity: inhalation

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Chromic acid

EC Number:

231-801-5

EC Name:

Chromic acid

Cas Number:

7738-94-5

Molecular formula:

CrH2O4

IUPAC Name:

dihydroxy(dioxo)chromium

Details on test material:

The test material is described as dark red flakes/granules

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LC50

Effect level:

167 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

>= 116 - <= 238

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

263 mg/m³ air (analytical)

Based on:

test mat.

95% CL:

>= 224 - <= 309

Exp. duration:

4 h

Effect levels 3

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.

Any other information on results incl. tables

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%

Applicant's summary and conclusion

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.