Selenium

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-07-09 to 1996-07-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Selenium

EC Number:

231-957-4

EC Name:

Selenium

Cas Number:

7782-49-2

Molecular formula:

Se

IUPAC Name:

selenium

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Se powder
- Substance type: inorganic

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HSD.Sprague-Dawley; Harlan Sprague Dawley, Inc., Indianopolis, IN
- Age at study initiation: 8 -12 weeks
- Weight at study initiation: Males (300-314 g); Females (190-225 g)
- Fasting period before study:
- Housing: Cages suspended, wire bottom, stainiess steel, one per cage.
- Diet (e.g. ad libitum): PMI Feeds™ Lab Diet Formula #5008, ad libitum
- Water (e.g. ad libitum): Municipal water supply from automatic water system, available ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 5°C
- Humidity (%): 30-80%
- Air changes (per hr): 10-12 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

IN-LIFE DATES: From: 1996-06-27 To: 1996-07-23

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

Exposure chamber
A 500 L nose-only stainless steel, dynamic flow inhalation chamber was utilized in this experiment. The body of the chamber has 25 ports in
5 rows. Polycarbonate cones are inserted into 10 designated individual ports. The test substance is introduced through the opening in the top of the chamber. The bottom section has a corresponding air outlet and a drain valve for cleaning the chamber.
The individual polycarbonate cones (tubes) are tapered at one end to fit the shape of the animal's head and the back portion is sealed with a
polycarbonate cap. The cones containing the animals tit tightly into the ports, and are sealed with "0" rings.

Generation of test atmosphere
The aerosol was generated by a Gem T Trost Air Mill which aspirated the test substance from a motorized revolving disc delivery system coupled
to the mill. The concentrated aerosol was then diluted with filtered air and drawn into the exposure chamber. Air flow into the chamber was
maintained through the use of a calibrated orifice plate at a rate of 1l.2 air changes per hour. Air flow was recorded at 30 minute intervals during
the exposure period, and was sufficient to ensure an oxygen content of at least 19%of the exposure attnosphere. Temperature and humidity were recorded at 30 minute intervalsduring the exposure period from a Taylor wet bulb/dry bulb hygrometer located in the exposure chamber.

Test substance administration
To prevent clogging of the aerosolization system, the test substance was oven-dried ad 60°C for 16hours prior to exposure. The animals were
exposed to an aerosol generated from the undiluted test substance (fine powder) for a period of four hours. When 99% concentration (t-99) was
attained, the animals which were individually housed in polycarbonite exposure tubes were inserted into a 500 L stainless steel nose-only
inhalation chamber for the specified exposure period. At the termination of the exposure period, the animals were returned to their stock
laboratory cages.

Camber operating parameters
Temperature: 23 °C
Humidy: 74 %
Air Flow: 93.4 (Lpm)
Trost Air Mill Setting: Air Port A, B Pressure: 80.20 psi
Sage Syringe Pump: 185-220% @ xl range
t-99 value - 25 min

Determination of concentration
The concentration of test substance in the exposure attnosphere (taken from the breathing zone of the animals) was determined gravimetrically
twice per hour and nominally at the end of the exposure.

Particle size distribution
Particle size, taken from the breathing zone of the animals, was determined twice during the exposure, using an Andersencascade impactor, at a
rate of 28.3 L/minute for a duration of 1 minute. The MMAD and particle size distributions are calculated from these data.

2 hour distribution MMAD 4.371 µm (Geometric standard derviation 1.992)
3.75 hour distribution MMAD 5.797 µm (Geometric standard derviation 2.116)
Average MMAD 5.084 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetrically

Duration of exposure:

4 h

Concentrations:

5.67 mg/L air

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and signs of pharmacologic and/or toxicologic effects were made frequently
on the day of exposure and at least once daily thereafter for 14 days. Individual body weights were recorded just prior to the inhalation exposure and on Days 7 and 14.
- Necropsy of survivors performed: yes; All study animals were subjected to gross necropsy, and all abnormalities were recorded.
- Other examinations performed: clinical signs, body weight

Statistics:

In order to calculate a mean exposure, the Mean Value Theorem of Calculus was used to properly weight the concentration, since the
concentrations could not be measured continuously. This method weights concentrations based on the time span of each concentration.
A concentration can be calculated for each minute, which better represents the exposure concentration received by each animal.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC0

Effect level:

5.67 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No animal died

Mortality:

There was no mortality during the study.

Clinical signs:

other: Prominent in-life observations included activity decrease, nasal discharge, piloerection, polyuria and salivation. Animals were asymptomatic by Day 2.

Body weight:

Body weight gain was largely unaffected by the administration ofthe test substance.
One female lost weight between Days 0 and 7; another female failed to gain weight between Days 7 and 14.

Gross pathology:

The gross necropsy conducted on each animal at termination of the study revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP; EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

The acute inhalation LC50 in male and female rats for Selenium (fine powder) is greater than 5.67 mg/L.

Executive summary:

In an acute inhalation toxicity study according to EPA OPP 81-3 (Acute inhalation toxicity), wistar rats (5 animals/sex) were exposed for four hours to an aerosol generated from the undiluted test substance (Selenium fine powder) at a level of 5.67 mg/L, nose only and observed for 14 days.

There was no mortality during the study. Clinical signs included activity decrease, nasal discharge, piloerection, polyuria and salivation, which were no longer evident by Day 2. Body weights were unaffected by exposure, except in two females. The gross necropsy revealed no observable abnormalities.

In conclusion, the acute inhalation LC₅₀in male and female rats for Selenium (fine powder) is greater than 5.67 mg/L.