Sodium hydrogensulphate

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:

supporting study

Study period:

Experimental Starting Date: 16-Mar-2010 Experimental Completion Date: 30-Mar-2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

Molecular formula:

H2O4S.2Na

IUPAC Name:

disodium sulfate

Constituent 2

Reference substance name:

Sodium Sulfate

IUPAC Name:

Sodium Sulfate

Details on test material:

IdeIdentification: Sodium Sulfate
Description (determined at Harlan Laboratories Ltd.) White powder
Cas Number: 7757-82-6
EINECS Number: 231-820-9
Batch Number: 20091001
Purity: ≥ 99.5%
Expiry Date (Retest Date): 30-Sep-2010

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories Ltd. Kreuzelweg 53 5961 NM Horst / Netherlands
- Age at study initiation: 9-10 weeks
- Weight at study initiation: females: 195.7 to 200.6 g, males: 244.7 to 273.6g
- Fasting period before study: none

- Housing: Animals were housed in groups of 3 of the same sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel" J. Rettenmaier & Söhne GmbH & Co KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland).
- Diet (e.g. ad libitum): Animals had ad libitum access to a pelleted standard Teklad rat maintenance diet (Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) batch no. 82/09, except during the period when the animals were restrained in exposure tubes.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum in water bottles, except during the period when they were restrained in exposure tubes.
- Acclimation period: for five days under laboratory conditions, after clinical health examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%):30 - 70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Animal Welfare

This study was performed in an AAALAC-accredited laboratory in accordance with the Swiss Animal Protection Law under license no. 397.

IN-LIFE DATES: From: To: 2010-03-16 to 2010-03-30

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A dust aerosol was generated from the test item using a rotating brush aerosol generator (CR3020) connected to a micronizing jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutralizer.
- Exposure chamber volume: not applicable
- Method of holding animals in test chamber: The animals were confined separately in restraint tubes which were positioned radially around the flow-past, nose-only exposure chamber
- Source and rate of air: compressed air was supplied by means of an oil free compressor and passed respiratory quality filters before it was introduced into the exposure system
- Method of conditioning air: respiratory quality filters
- System of generating particulates/aerosols: A dust aerosol was generated from the test item using a rotating brush aerosol generator (CR3020) connected to a micronizing jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutralizer.
- Method of particle size determination: Mercer impactor
- Treatment of exhaust air: filtered
- Temperature, humidity, pressure in air chamber: 22.5°, 4.8% rel humidity, 20.6 % oxygen

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric determinations of aerosol concentration were performed five times during exposure. The samples were collected on a Millipore®durapore filter, Type HVLP loaded in a 47 mm in-line stainless steel filter sampling device. The filters were weighed before and immediately after sampling using a calibrated balance. The test aerosol concentration was calculated from the amount of test item present on the filter and the sample volume.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): no vehicle used
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.65/2.67/2.71 ym, GSD: 0.991/0.994/0.995

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

gravimetric: 2.4 mg/L air
nominal: 9.1 mg/L air

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for viability were recorded once before exposure on the day of exposure (test day 1), three times during exposure, immediately, 1 h and 3 h after exposure on test day 1 and twice daily during the observation period. Each animal was examined three times during exposure, immediately and 1 h after exposure on test day 1 and once daily during the observation period. Observations were detailed and carefully recorded using explicitly defined scales as appropriate. Only grossly abnormal signs were detectable during exposure, as the animals were restrained in the exposure tubes. The body weight of each animal was recorded on test days 1 (before exposure), 2, 4, 8 and 15 (before necropsy).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Statistics:

no

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.4 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

none

Clinical signs:

other: (See Individual Tables on p 26 in the attached "Figures & individual tables"). All animals survived the scheduled observation period. Ruffled fur was recorded in all animals one 1 hour after the end of exposure and on day 2. There were no clinical signs f

Body weight:

Body Weights
(See Individual Tables on page 32 in the attached "Figures & individual tables").
From test day 1 to test day 2, slight body weight loss was noted in two females, stagnation of body weight was recorded in the males and one female. Thereafter normal body weight development was recorded in the males and one female. Stagnation of body weight was observed in one female from day 2 to test day 4 and from test day 8 to test day 15. Slight body weight loss was recorded in another female from test day 2 to test day 4. Thereafter normal body weight development was noted in this female.

Gross pathology:

(See Individual Tables on p 35 in the attached "Figures & individual tables").
There were no macroscopic findings during necropsy.

Other findings:

none

Any other information on results incl. tables

Test Atmosphere Conditions

Temperature, relative humidity and oxygen concentration during exposure were considered to be satisfactory for this type of study.

Data on temperature, relative humidity and oxygen concentration are presented in the following table.

The first relative humidity measurement of exposure (marked with a *) was excluded from the calculation of the mean. This was considered not to represent the relative humidity of the test atmosphere. Slight humidity in the cotton wick protecting the probe from test aerosol adhesion or slight humidity from ambient air around the probe may have affected these measurements at the beginning of exposure and shortly afterwards

  

Recording Time [hours:min]	O2Concentration [Vol %]	Temperature [°C]	Relative Humidity [% RH]
06:15 06:45 07:15 07:45 08:15 08:45 09:15 09:45 10:15 10:20 Mean St. Dev. N	20.7 20.7 20.6 20.6 20.6 20.6 20.6 20.6 20.6 20.6 20.6 0.0 10	22.3 22.5 22.5 22.6 22.5 22.7 22.6 22.7 22.6 22.6 22.5                            0.1  10	21.7* 5.2 4.5 5.4 4.4 5.6 4.3 5.0 4.3 4.3 4.8 0.5 9

Determination of Aerosol Concentrations

The gravimetric aerosol concentration determined was 2.4 mg/L air as targeted. The aerosol concentration was stable during the exposure period. Data on gravimetric aerosol concentration are presented in the following table:

The nominal aerosol concentration was 9.1 mg/L air.

 

Sampling   Time [hours:min]	Sampling Volume [L]	Amount of Test Item on the Filter [mg]	Gravimetric Aerosol Concentration [mg/L air]
06:25 – 06:30	5.0	11.578	2.4
07:30 – 07:35	5.0	11.755	2.4
08:30 – 08:35	5.0	11.671	2.4
09:30 – 09:35	5.0	10.652	2.2
09:55 – 10:00	5.0	11.544	2.4
Mean			2.4
St. Dev.			0.1
N			5

  

Particle Size Distribution

The Mass Median Aerodynamic Diameters (MMAD) obtained from three gravimetric

measurements of particle size distribution during the exposure were similar (MMAD = 2.71 μm, 2.65 μm and 2.67 μm). This led to the conclusion that the particle size of the generated aerosol was fairly stable during the whole exposure period. The MMADs were within the target range of 1 to 4 μm, thus deposition of the particles can be assumed to have occurred in both the upper and the lower respiratory tract. Hence, the particle size distribution and MMADs obtained were considered to be appropriate for acute inhalation toxicity testing.

Data on particle size distribution are presented in the attached table “Particle Size Distribution”:

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

In conclusion, the LC50 of Sodium Sulfate obtained in this study was estimated to be greater than 2.4 mg/L air (gravimetrically determined mean aerosol concentration) which was the highest technically feasible aerosol concentration. There was no indication of relevant sex-related differences in toxicity of the test item.

Executive summary:

A group of three male and three female albino rats [HanRcc:WIST(SPF)] was exposed by nose-only, flow-past inhalation for four hours to the test item at agravimetricallydetermined mean concentration of 2.4 mg/L air.All animals were observed for clinical signs and mortality during the inhalation exposure and theobservation period of 14 days. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 2, 4, 8 and 15 before necropsy. On day 15 all animals were sacrificed and necropsied.

The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats.

 

All animals survived the scheduled observation period.

 

Ruffled fur was recorded in all animals one hour after the end of exposure and on test day 2. From test day 3 onwards no clinical signs were observed.

 

Slight effects on body weight were recorded during the observation period.

 

There were no macroscopic findings during necropsy.

 

 

In conclusion, the LC₅₀ of Sodium Sulfate obtained in this study was estimated to be greater than 2.4 mg/L air (gravimetrically determined mean aerosol concentration) which was the highest technically feasible aerosol concentration.There was no indication of relevant sex-related differences in toxicity of the test item.