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

Endpoint summary

Description of key information

oral, rat, comparable to OECD 401, LD50 = 3530 mg/kg bw/d

inhalation, rat, acc to OECD 403, GLP, LC50 < 4.58 mg/L

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: Proprietary study, reported in summary form only but in sufficent detail to allow reliable interpretation of the adequacy of the method and results

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study is not reported in great detail but appears to be broadly comparable to OECD 401; bodyweights were not measured and gross necropsy not performed.

GLP compliance:

no

Remarks:

study pre-dates GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Male Wistar rats (160-180 g) were obtained from Winkelmann (Germany) and were group housed (5 animals/cage)

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

No further details

Doses:

1000, 3100, 3500, 4000, 4500 and 5000 mg/kg bw

No. of animals per sex per dose:

10 males

Control animals:

no

Details on study design:

No further details

Statistics:

LD50 calculation according to the method of Fink & Hund (Arzneimittel-Forschung 15, 624; 1965)

Preliminary study:

Not reported

Sex:

male

Dose descriptor:

LDLo

Effect level:

3 100 mg/kg bw

Remarks on result:

other: 1/10 rats

Sex:

male

Dose descriptor:

LD50

Effect level:

3 530 mg/kg bw

95% CL:

3 190 - 3 790

Sex:

male

Dose descriptor:

LD100

Effect level:

5 000 mg/kg bw

Mortality:

Deaths occured at 3100 mg/kg bw (1), 3500 mg/kg bw (7), 4000 mg/kg bw (7), 4500 mg/kg bw (9) and 5000 mg/kg bw (10).

Clinical signs:

other: Signs of toxicity (emaciation, red staining of the eyes and nose, reduction in common parameters) were seen in all animals at dose levels of 3100 mg/kg bw and greater

Gross pathology:

Not reported

Other findings:

No other findings are detailed

The results of the study are tabulated below. The LD50 in male rats was found to be >3100 mg/kg bw and was calculated to be 3530 (3190 -3790) mg/kg bw.

Dose level (mg/kg bw)	No. animals	Signs of toxicity	Deaths	Time of death
1000	10	-	-	-
3100	10	10	1	3h
3500	10	10	7	2-9d
4000	10	10	7	2-5d
4500	10	10	9	2-7d
5000	10	10	10	2-4d

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test material was calculated to be 3530 mg/kg bw. Classification for acute oral toxicity according to current EU criteria is not required.

Executive summary:

In a study comparable to OECD Test Guideline 401 Wistar rats (10 males/group) were gavaged with a single dose of the test material (in water) at dose levels of 1000, 3100, 3500, 4000, 4500 or 5000 mg/kg bw and observed for 14 days. Deaths occurred at 3100 mg/kg bw (1), 3500 mg/kg bw (7), 4000 mg/kg bw (7), 4500 mg/kg bw (9) and 5000 mg/kg bw (10) within 9 days of exposure. Signs of toxicity (emaciation, red staining of the eyes and nose, reduction in common parameters) were observed at dose levels of 3100 mg/kg bw and above. The LD50 was calculated to be 3530 (3190 -3790) mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 530 mg/kg bw

Quality of whole database:

sufficient quality of the database

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

Study period:

19 May to 18 September 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 12 May 1981

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

1998

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

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

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.

Preliminary study:

Not applicable.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4 580 mg/m³ air

Physical form:

inhalation: dust / mist

Quality of whole database:

sufficient quality of the database

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An acute oral toxicity study is available for the material 'Chromsal B' (chromium hydroxide sulphate / sodium sulphate), which shows low toxicity. This study was reported briefly, but in sufficient detail to enable confident evaluation of the method and the reliability of the results. The calculated LD50 from this study of 3530 mg/kg bw shows that the substance is of low toxicity by this route.

An acute inhalation study was performed according to OECD Test Guideline 403 and GLP. 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 persistent 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.

Justification for classification or non-classification

Based on the available results the registered substance is classified as Acute tox 4 (H332: Harmful if inhaled) according to Regulation (EC) No 1272/2008.