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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

1. Both substances are inorganic salts of a monovalent cation from Group 1A of the periodic table, and triphosphoric acid. Thus, they share the Na+ or K+ cation and P3O105- anion.
2. Both the Na+ and the K+ cation have a similar biological function and therefore triphosphate salts of these types are not considered to differ in their systemic toxicity profile; differences arise in their local effects profile due to the increasing or decreasing acidity/alkalinity and buffering capacities of the substances. This has been shown not to have an effect on systemic toxicity.
3. In addition, both salts have been shown to be of similar low toxicity in acute oral studies and therefore comparisons can be drawn to allow read-across for the acute inhalation endpoint

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.

4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’.
Cross-reference
Reason / purpose for cross-reference:
read-across: supporting information

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Pentasodium triphosphate
EC Number:
231-838-7
EC Name:
Pentasodium triphosphate
Cas Number:
7758-29-4
Molecular formula:
Na5P3O10 H5-xP3O10Nax (where x is approximately 5) 6H2O.Na5P3O10
IUPAC Name:
Pentasodium triphosphate
Details on test material:
- Name of test material (as cited in study report): Sodium tripolyphosphate
- Substance type: White powder
- Purity: >90%
- Lot/batch No.: B5885327C

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Kent, UK
- Weight at study initiation: ~ 200 g
- Housing: Cages were made of polypropylene (size 38 cm x 56 cm x 18 cm height) and had detachable wire mesh tops and floors
- Diet: Free access to a measured excess amount of food (Labsure LAD 1)
- Water: Free access to water
- Acclimation period: At least 5 days prior to exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Max (23) Min (19)
- Humidity (%): 63



Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A Wright dust generator
- Exposure chamber volume: 120 L
- Method of holding animals in test chamber: Rats were held in cages of stainless steel mesh partitioned to provide 10 individual animal compartments
- Method of conditioning air: The test atmosphere produced by the generator was passed through a glass elutriation column to reduce, by sedimentation the amount of non-respirable particulate.
- Method of particle size determination: Anderson mini-sampler
- Temperature in air chamber: Mean air temperature: 23.2°C(control) 22.6 °C (test).
- Relative humidity in air chamber: Mean relative humidity: 39% (control) 41% (test)

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.39 mg/L (highest attainable concentrations)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighed daily until the end of the observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, lung weights

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.39 mg/L air
Exp. duration:
4 h
Mortality:
There were no deaths.
Clinical signs:
other: During exposure: signs consistent with exposure to an irritant dust. Partial closing of the eye, exaggerated respiratory movements, restless behaviour and excessive grooming were seen in all exposed rats. During observation period: There were no clinical
Body weight:
Small losses in body weight or a decrease in the rate of body weight gain were observed for a proportion of male rats on the day following exposure. The losses in the male rats were statistically significant 9P<0.05)
Gross pathology:
The lung weight to body weight ratio for all rats was within normal limits. Grey areas were seen ion the lungs of 1 male rat exposed to the test substance. There were no abnormalities in any other rats.
Other findings:
Food and water consumption: Food consumption was reduced for 1 day in male rats and slightly reduced for 1 day in female rats following exposure. Water consumption was slightly reduced for 1 day in male rats following exposure.

Any other information on results incl. tables

Table 1: Concentrations of sodium tripolyphosphate (Gravimetric determination):

Sample

Time

Amount in air (mg/L)

2.1

0 h:30 m

0.53

2.2

1h:00m

0.50

2.3

2h:00m

0.35

2.4

3h:00m

0.29

2.5

3h:50m

0.27

Mean

0.39

SD

0.120

The mean concentration of sodium tripolyphosphate was 0.39 mg/L and was the highest attainable. The concentration achieved indictaes that the test susbstance contains only a low proportion of small particles.

Table 2: Particle size distribution of sodium tripolyphosphate:

Sample

Time

Stage

Particle size range (µm)

Amount collected (mg)

% of total

% respirable

PSD 1

1h:30m

1

>5.5

1.00

64.9

35.1

2

3.5-5.5

0.16

10.4

3

2.0-3.5

0.20

13.0

4

0.3-2.0

0.10

6.5

Filter

0.3

0.08

5.2

Totals

1.54

100.0

PSD 2

3 h:30m

1

>5.5

0.64

81.0

19.0

2

3.5-5.5

0.02

2.5

3

2.0-3.5

0.09

11.4

4

0.3-2.0

0.04

5.1

Filter

0.3

0.00

0.0

Totals

0.79

100.0

The results in table 2 show that on average 27% of the dust collected was 5.5 µm or less in aerodynamic diameter and therefore of respirable size.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the test material caused no mortality when administered for 4 h to Wistar rats at a mean, maximum attainable concentration of 0.39 mg/L air. Based on this, the LC50 for the test material is considered to be greater than 0.39 mg/L. This study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement for this endpoint.

As the study was conducted up to the maximum attainable concentration and in accordance with Regulation (EC) No. 1272/2008 (EU CLP) pentasodium triphosphate is not considered to be classified.
Read across from pentasodium triphosphate to pentapotassium triphosphate is justified on the following basis:
Both substances are ionic inorganic compounds containing a triphosphate anion and a group 1 alkali metal cation. Both the Na+ and the K+ cation have a similar biological function and therefore triphosphate salts of these types are not considered to differ in their systemic toxicity profile; differences arise in their local effects profile due to the increasing or decreasing acidity/alkalinity and buffering capacities of the substances. This has been shown not to have an effect on systemic toxicity.
In addition, both salts have been shown to be of similar low toxicity in acute oral studies and therefore comparisons can be drawn to allow read-across for the acute inhalation endpoint.

This study is therefore deemed reliable for classification and labeling according to Regulation (EC) No 1272/2008 (EU CLP) and further testing is considered to be scientifically unjustified.