Chromium trinitrate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

19 May to 11 June 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline compliant GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Chromium hydroxide sulphate

EC Number:

235-595-8

EC Name:

Chromium hydroxide sulphate

Cas Number:

12336-95-7

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Chromium hydroxide sulphate, a green powder, batch number 02.02.2009, purity 25.5 Cr2O3. Stored in a sealed container at room temperature.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were male and female Han Wistar rats, obtained from Harlan UK Ltd. The animals were weight matched to 200 g ± 15% on arrival and were less than 12 weeks of age at the start of the study.
They animals were housed in groups of five. The room provided a minimum of 15 air changes per hour, temperature was maintained at 19 to 25°C and relative humidity was maintained at 40 to 70 %. The animals were removed from this environment during acclimatisation to tube restraint and during test article exposure. Fluorescent lighting was provided on a 12 hour light/dark cycle.
The rats were provided with wooden 'Aspen' chew blocks as enrichment. They were fed SQC Rat and Mouse Maintenance Diet No.1, Expanded (SDS Ltd., UK) ad libitum. Mains water was provided ad libitum.
All animals were examined for ill health on arrival. They underwent 9 days acclimatisation, the final 3 days of which they underwent acclimatisation to restraint tubes.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The test aerosol was generated from the test article, chromium hydroxide sulphate, using a Rotating Brush Generator into a flow-through (nose only) exposure chamber of approximately 40 L volume. The air flow was 14 L/min and provided 12 air changes per hour.
The rats had Vaseline petroleum jelly smeared over their closed eyelids prior to test article exposure as a precautionary measure to avoid adverse irritant effects to the eye.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The achieved aerosol concentration was measured gravimetrically prior to and at approximately half-hourly intervals throughout the exposure.

Duration of exposure:

4 h

Concentrations:

Nominal concentration = 43.3 mg/L. The mean achieved aerosol concentration = 4.58 mg/L, with a range of 3.45 to 5.98 mg/L.

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

Five male and five female rats underwent 4 hour nose-only inhalation exposure to the test compound. The dose level initially selected was 5 mg/L to represent the limit dose. All animals were observed daily (for 14 days post-exposure) for signs of ill health or overt toxicity. Animals were observed approximately hourly during the exposure period and for the remainder of the exposure day. Individual body weights were recorded before and after exposure on Day 1, and on Days 2, 8 and 15. Additional body weights were recorded on Days 3, 4 and 5.
All animals were subject to a gross necropsy.

Statistics:

Not performed.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

< 4.58 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

6/10 animals were terminated prematurely due to the severity of the clinical signs observed: 1 male and 1 female were terminated on Day 1; 1 female was terminated on Day 3, a second on Day 7 and a third on Day 8; 1 male was terminated on Day 11. One male was found dead on Day 10.

Clinical signs:

other: Severe clinical signs were observed in the majority of the animals, and persisted throughout the observation period. Signs included: gasping, rales, vocalisation, dyspnoea, hunched posture, unkempt coat, piloerection, hypothermia, semi-closed eyes, and di

Body weight:

All animals lost body weight following exposure to the test article. Most decedent animals steadily lost weight until their day of death, with some losing 31-34% of the pre-exposure body weight. Surviving animals started to gain weight from Day 5, although none reached their pre-exposure weight by the end of the observation period.

Gross pathology:

Macroscopic findings were generally unremarkable, except dark lungs were noted in one male and three female decedents.

Other findings:

The mean particle size distribution (MMAD ± GSD) was 3.12 µm ± 1.79. 42.9-63.1% of the particles were below 3.5 µm in diameter.

Any other information on results incl. tables

The LC50 is considered to be below 4.58 mg/L.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LC50 is considered to be below 4.58 mg/L.

Executive summary:

Male and female Han Wistar rats underwent a single 4 -hour nose only inhalation exposure to chromium hydroxide sulphate at a mean atmospheric exposure level of 4.58 mg/L. The test compound was poorly tolerated, causing persistant clinical signs. Seven out of ten animals died during the course of the study. The LC50 is therefore considered to be below 4.58 mg/L.