Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): Sodium Hexametaphosphate
Analytical purity: not determined
Lot #: B571PP002
FMC-T#1037
Storage: Room temperature
Description: Fine White powder
Physical state: Solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain Reference: Sprague-Dawley (Crl:CDBR VAF Plus)
- Source: Charles River Laboratories, Kingston, NY
- Age at study initiation: The actual age of the rats was not specified, only that they were young adults.
- Weight at study initiation (± SD): Males: 281 ± 9.4 g; Females: 243 ± 15.7 g
- Fasting period before study: No data
- Housing: Animals were housed individually in stainless steel suspended rat cages. Deosorb bedding was used in the litter pans.
- Diet: Purina Laboratory Rodent Chow 5001 available ad libitum
- Water: Tap water available ad libitum
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23 °C (quoted in the study as 69 - 73 °F)
- Humidity (%): 41 - 70%
- Air changes (per hr): 14.0 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h fluorescent light and 12 h dark cycle

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The Rochester type exposure chamber was made of stainless steel and glass and was operated dynamically. The calculated 99% equilibrium time for the chamber at a flow rate of 35.0 L per minute was 19.7 minutes (equivalent to 14.0 "air changes per hour").
- Exposure chamber volume: 150 L
- Method of holding animals in test chamber: The test animals were assigned to and housed in individual compartments of a wire mesh cage bank (all on the same horizontal level) during the exposure.
- Source and rate of air: Breathing grade compressed air was used and the total chamber air flow rate was 35.0 L/minute.
- Method of conditioning air: No data
- System of generating particulates/aerosols: The test material was generated using a BGI Wright Dust Feeder II. The test material was desiccated and packed into large dust cups. Breathing Grade compressed air was metered to the Wright dust feeder through teflon tubing by a Matheson® 605 rotameter with a metal float. Rotameter back pressure was controlled using a Matheson® 3104C regulator. The dust feeder back pressure was monitored using a Marshalltown® back pressure gauge. The test material was made airborne by the compressed air dispersing the material into the exposure chamber. The concentration of the test atmosphere was controlled by the delivery rate setting of the Wright dust feeder.
- Method of particle size determination: The samples were drawn through a Sierra 218 cascade impactor at 2.78 liters per minute. The aerodynamic particle size distribution was determined by gravimetric analysis of the amount of test material collected on the impactor stages and subsequent determination of the mass median aerodynamic diameter (MMAD), geometric standard deviation and other particle size parameters by logarithmic-probability plotting.
- Treatment of exhaust air: The chamber air was exhausted from the bottom of the chamber and passed through an orifice tube system which continuously monitored airflow and then through a commercial filter box. The filter box was connected to a line leading to additional filters and an exhaust fan on the roof. The exhaust operated at a flow rate of 35.0 liters per minute, creating a slight negative pressure in the chamber, which was considered to be the total chamber air flow rate. The entire exposure system and primary exhaust filter were contained in a fume hood.
- Temperature, humidity, pressure in air chamber: The mean temperature and relative humidity in the chamber were 19.44 °C (67±1.5 °F) and 63±3.8%, respectively. The pressure in the air chamber was not measured.


TEST ATMOSPHERE
- Brief description of analytical method used: The airborne concentration of the test material was determined gravimetrically.
- Samples taken from breathing zone: Yes - Chamber air samples were taken on glass fiber filters held in cassettes at approximately one hour intervals during the exposure to determine the airborne concentration of test material. The airborne concentration of the test material was determined gravimetrically by drawing a known amount of chamber air through the filter. The samples were taken from the center of the chamber directly over the animal exposure caging.
The difference between gravimetric and nominal concentration was attributed to sedimentation of larger particles and/or adhesion of the test material to surfaces in the exposure chamber.

VEHICLE
- Not applicable: The test material was administered as received and a vehicle was not used.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The fraction of particles less than or equal to 1 µm in mass aerodynamic diameter, based on the log-probability graphs, ranged from 0.8 to 12.2%. The fraction of particles less than or equal to 10 µm in mass aerodynamic diameter, based on the log probability graphs, ranged from 78.9 to 86.4%. These results indicated the test material was respirable in size to the rat.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMADs ranged from 3.25 to 4.98 micrometers (µm) with geometric standard deviations ranging from 2.38 to 2.78. The MMAD represents the smallest size that could be achieved in this study. The material is hygroscopic causing the particles to agglomerate and/or adhere to surfaces inside the chamber. Several trials were initially performed with various generation schemes and the system which was ultimately chosen provided the best performance.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal concentration: 12.68 mg/L (maximum attainable concentration)
Gravimetric concentration: 3.698 ± 0.288 mg/L
No. of animals per sex per dose:
5 animals/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for signs of toxicity and mortality every 15 mins during the first hour of exposure, hourly for the remainder of the exposure, upon removal from the chamber, at 1 h post-exposure, twice daily thereafter for 13 days and once on day 14. Individual body weights were recorded on days 0, 1, 2, 4, 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: See Table 1 for a list of recorded observations.
Statistics:
No data

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.69 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
None of the animals died as a result of dosing.
Clinical signs:
other: See Table 1. Clinical signs noted during the exposure included lacrimation, oral discharge and squinting eyes. Clinical signs noted upon removal from the chamber and at one hour post exposure included abdominogenital staining, chromodacryorrhea, chromorhi
Body weight:
See Table 2 and 3.
All animals lost weight through day 1 of the study and then began to gain weight in a normal pattern. At termination all animals exhibited increased in body weight over their day 0 values.
Gross pathology:
See table 3.
There were no gross internal lesions observed in any animal.
Other findings:
No data

Any other information on results incl. tables

See attached tables.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute inhalation median lethal concentration (LC50) of the test material in male/female Sprague-Dawley rats was estimated to be greater than 3.69 mg/ L of air. The study was conducted up to a maximum attainable concentration and can therefore be considered to be equivalent to a limit test conducted at 5 mg/ L. As such, sodium metaphosphate is not classified for inhalation toxicity, in accordance with Regulation EC (No.) 1272/2008 (EU CLP). This study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement for this endpoint.


Executive summary:

Introduction

The study was performed to assess the acute inhalation toxicity of the test material in the Sprague-Dawley rat. The method was designed to meet the requirements of the follwing:

OECD Guideline 403 (Acute Inhalation Toxicity)

EU Method B.2 (Acute Toxicity (Inhalation))

EPA OPP 81-3 (Acute inhalation toxicity)

Method

Five male and five female animals were exposed for a period of 4 hours to the maximum attainable concentration of the dust (test material). The analytical dose of the test material was determined to be 3.69 ± 0.288 mg/ L air. Clinical signs, bodyweight and mortality were monitored during the study, after 14 days surviving animals were subjected to gross necropsy.

Mortality

There were no deaths.

Clinical Observations

Clinical signs noted during the 14 day post-exposure observation period included alopecia on head, chromodacryorrhea, chromorhinorrhea, decreased feces and exophthalmos.

Bodyweight

All animals lost weight through day 1 of the study and then began to gain weight in a normal pattern. At termination all animals exhibited increased in body weight over their day 0 values.

Necropsy

No abnormalities were noted

Conclusion

The study was conducted up to a maximum attainable concentration and can therefore be considered to be equivalent to a limit test conducted at 5 mg/ L [actual result LC50>3.96 mg/ L]. As such, sodium metaphosphate is not classified for inhalation toxicity (EU CLP - Unclassified).