Chromium trinitrate

Endpoint summary

Description of key information

Acute LD50 (oral, rat): 2363 mg/kg bw (as average of 2 results - 1475 mg/kg bw and 3250 mg/kg bw - in a weight of evidence approach)
Acute LC50 (inhal., rat): < 4.58 g/m3 (7/10 animals died during the course of the study --> classified as acute inhalative toxic, category IV according to CLP)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 363 mg/kg bw

Quality of whole database:

2 publications reporting on the acute toxicity of chroium nitrate nonahydrate were used in a weight of evidence approach and the average LD50 is used for hatzard and risk assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

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

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.

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.

Preliminary study:

Not applicable.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4 580 mg/m³ air

Quality of whole database:

only one inhalative study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

Acute oral toxicity of chromium trinitrate was investigated by two research groups (Smyth et al. 1969 and Vernot et al.1977). Although Vernot et al. were using the methodology developed by Smyth et al. before, the results for chromium trinitrate differed significantly. Whereas, Smyth et al. reported an experimentally determined LD50 by gavage of 3250 mg/kg bw, Vernot et al reported 1540 mg/kg bw for male and 1410 mg/kg bw for female rats (average of 1475 mg/kg bw). For hazard and risk assessment both studies were combined in a weight of evidence approach and the average LD50 of 3250 (Smyth) and 1475 (Vernot) being 2363 mg/kg bw is taken forward for hazard and risk assessment.

Acute inhalative toxicity

No data for chromium trinitrate on inhalative toxicity is available but on another soluble chromium(III) compound, chromium hydroxide sulphate, having very similar toxicological ecotoxicological and phys-chem properties to chromium trinitrate. In an inhalative study rats were dosed nose only for four hours to chromium hydroxide sulphate as aerosol in a limit test. At a mean achieved analytically verified aerosol concentration of 4.58 mg/L (5 mg/L nominal) 6 out of 10 animals were terminated prematurely due to the severity of clinical signs observed (2 animals on day 1, 1 animal on day 3, one on day 7, one on day 8 and one on day 11. One animal was found dead on day 10. 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 distended abdomen. During the inhalation exposure, all animals exhibited laboured breathing and/or slow breathing. Most animals had green staining around the head mouth and nose following exposure on Day 1. Based on these finding, it is concluded that chromium(III) compounds such as chromium trinitrate and chromium hydroxy sulphate are harmful by inhalation and are classified accordingly into category 4 for acute inhalative toxicity according to CLP.

Acute dermal toxicity

No data on dermal acute toxicity to chromium trinitrate or surrogate chromium(III) compounds for read-across could be identified. It appears according to the US EPA Health Assessment Document for Chromium, July 1983 that chromium(III) compounds, when in contact with skin, combine with proteins in the superficial layers but do not cause ulceration (National Academy of Science, 1974, Medical and Biological Effects of Environmental Pollutants: Chromium. Washington D.C., National Academy Press).

Acute toxicity other routes

In a publication investigating toxicokinetics of chromium(III) and chromium(VI) compounds intraperitoneal toxicity of chromium(III) nitrate was investigated, resulting in much lower LD50 values than compared to acute oral toxicity. This supports the low absorption of chromium trinitrate as described in the toxicokinetic assessment and shows that once chromium(III) become bioavailable it increases significantly in toxicity.

Justification for selection of acute toxicity – oral endpoint
weight of evidence approach used based on 2 reliable publications, following the same methodology.

Justification for classification or non-classification

Based on acute toxicity data for oral exposure chromium trinitrate is not subject to classification according to CLP (Regulation EC No 1272/2008) or DSD (Directive 67/548/EEC). However, based on finding upon inhalative exposure towards a surrogate chromium(III) compound chromium hydroxy sulphate, chromium trinitrate is to be classified into category IV for inhalative toxicity according to CLP, respectively Xn, R20 according to DSD. Data for dermal toxicity are lacking and thus no classification is possible for dermal toxicity.

Specific target organ toxicity was not observed other than effect leading to mortality in the inhalative study and thus STOT SE classification in not required. Aspiration hazard classification is not applicable to inorganic salts and therefore conclusively not required.