Reaction mass of chromium (+ 3) hydroxide sulfate and sodium sulfate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 May to 18 September 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 12 May 1981

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF Japanese MAFF Agrochemical Test Guidelines 12 Nohsan 8147

Version / remarks:

2-1-12, 24 November 2000 and revision of 24 June 2001

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

Molecular formula:

CrHO5S

IUPAC Name:

chromium hydroxide sulphate

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:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable) : Han Wistar rats
- Source: Harlan UK Ltd
- Age at study initiation: less than 12 weeks
- Weight at study initiation: 200 g ± 15%
- Housing: in groups of five
- Diet (e.g. ad libitum): SQC Rat and Mouse Maintenance Diet No.1, Expanded (SDS Ltd., UK) ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: 9 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 40 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12hrs/12hrs

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: approximately 40 L
- Source and rate of air (airflow): 14 L/min
- System of generating particulates/aerosols: Rotating Brush Generator into a flow-through
- Method of particle size determination: gravimetrically using a Marple 298 Cascade impactor
- Temperature and humidity in air chamber: 20.8 °C, 21.1 %

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: 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.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 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.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The protocol range for the particle size distribution is 1 – 4μm MMAD and 1 – 3 GSD

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:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed daily for signs of ill health or overt toxicity. Weighing Day1, 2, 3, 7, 8, 9 and 14
- Necropsy of survivors performed: Yes, all animals were subject to a gross necropsy.
- Clinical signs including body weight: Huntched posture, unkempt, rales and piloerection were observed from most of the test group
- Other examinations performed: organ weights, histopathology

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)

Based on:

test mat.

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: gasping, rales, vocalisation, dyspnoea, hunched posture, unkempt coat, piloerection, hypothermia, semi-closed eyes, and distended abdomen

Remarks:

for detailed information please refer to field 'Any other information'

Body weight:

- greater than 10% body weight loss : Most decedent animals steadily lost weight until their day of death, with some losing 31-34% of the pre-exposure body weight.

All animals lost body weight following exposure to the test article. 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.

Any other information on results incl. tables

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

Clinical signs

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

Applicant's summary and conclusion

Conclusions:

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

Executive summary:

An acute inhalation toxicity study according to OECD Test Guideline 403 under GLP was performed in rats. Five male and five 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.