Dizinc pyrophosphate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Jan 2017-01 Feb 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Adopted 7 Sep 2009

Deviations:

yes

Remarks:

2 males and 4 females were dosed. GSD out of range. Relative humidity of test material out of range. Temperature/RH in animal room sporadically out of range. No impact on the study results.

GLP compliance:

yes (incl. QA statement)

Remarks:

Entitad Nacional de Acreditaciόn, Madrid, Spain

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dizinc pyrophosphate

EC Number:

231-203-4

EC Name:

Dizinc pyrophosphate

Cas Number:

7446-26-6

Molecular formula:

H4O7P2.2Zn

IUPAC Name:

dizinc(2+) (phosphonooxy)phosphonate

Test material form:

solid: particulate/powder

Details on test material:

- Other: white, odourless

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Specific Pathogen Free

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, C/Argenters 7, Local AB, 08290 Cerdanyola del Vallés, Barcelona, Spain
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 261.9-273.5 g (males) and 196.0-217.5 g (females)
- Fasting period before study: not specified
- Housing: group housed 3-4 per cage with Capsumlab Lecho_10 (autoclavable) bedding, and enrichment devices (nesting material, tubes, and chew blocks)
- Diet: Global diet 2914C, Harlan Teklad, Station Road, Blackthorn, Bicester, Oxon, OX25 1TP, UK, ad libitum
- Water: tap water in water bottles, ad libitum
- Acclimation period: at least 7 days, with 90 min to the nose-only restraining tubes on the day of exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 1.5
- Humidity (%): 20-43
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 Jan 2017 To: 01 Feb 2017

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

ca. 2.37 µm

Geometric standard deviation (GSD):

ca. 6.71

Remark on MMAD/GSD:

MMAD during exposure was 2.37 μm (average of three particle size determinations). This value is within the respirable range (1-4 μm) and appropriate for acute inhalation toxicity testing. GSD was above the upper limit of 3 in the second and third particle size determinations, indicating that the particle size distribution of the aerosol generated throughout the 4-hour exposure period was not homogeneous. Nevertheless, at the highest concentration of test material technically achievable (4.73 mg/L, gravimetric determination) the mean percentage of particles below the upper limit of 4 μm, over the whole exposure period, was 66% (79%, 67% and 52.5% for particle size determinations #1, 2 and 3, respectively), and this value was considered acceptable.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow-past, nose-only exposure chamber made of anodised aluminium
- Exposure chamber volume: approximately 3 L
- Method of holding animals in test chamber: rats were individually exposed in glass tubes matching their size, positioned radially around the exposure chamber
- Source and rate of air: clean air with a flow rate at each exposure tube of approximately 1 L/min
- Method of conditioning air: filtered air from a compressor
- System of generating particulates/aerosols: a dust aerosol was generated from the desiccated test material using a rotating brush aerosol generator (RBG 2000, PALAS GmbH, Germany) and conveyed via glass tubing from the generator to the exposure chamber; aerosol concentration was determined by gravimetric analysis.
- Method of particle size determination: MMAD and the GSD were determined on results from a PIXE cascade impactor, using Microsoft Excel® software (Microsoft Corporation, USA).
- Treatment of exhaust air: not specified
- Temperature, humidity, pressure in air chamber: Temperature and relative humidity in the chamber were measured continuously during exposure using a thermohygrometer (Kimoth110, Kimo). The target range for temperature was 19-25 °C, the target range for relative humidity (RH) was 30-70%. The exposure airflow rate was adjusted using the pressure difference over a Venturi tube. Target flow range was 0.5-1.0 L/min through each inhalation tube.

TEST ATMOSPHERE
- Brief description of analytical method used: Three gravimetric measurements were taken during exposure to measure exposure concentration. The sampling flow was similar to the air flow rate per exposure port. Test aerosol samples were collected for 2 min periods onto a Whatman filter (grade F319-04) using a filter sampling device. The filters were weighed before and immediately after sampling using a calibrated balance. The gravimetric aerosol concentration was calculated from the amount of test material present on the filter and the sample volume.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Determined gravimetrically three times during the exposure. The cumulative particle size distribution of the test aerosol was determined using a PIXE cascade impactor, measured by gravimetric analysis of the test material deposited on each stage of the cascade impactor.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD and GSD were calculated on the basis of results from the impactor using Microsoft Excel® software (Microsoft Corporation, USA). Target ranges were 1 to 4 µm for the MMAD, and 1.5 to 3 for the GSD.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Exposure concentration was the highest technically achievable concentration (4.73 mg/L)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

ca. 4 h

Concentrations:

5 mg/L (nominal)
4.73 mg/L (analytical)

No. of animals per sex per dose:

2 males and 4 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: hourly during exposure (only grossly abnormal signs), immediately and 1 h after exposure, and once daily thereafter until the end of the observation period. All animals were observed for a period of 14 days after administration. All animals were weighed on the day of treatment just before starting exposure (study day 1), on study days 2, 4, 8 and immediately before sacrifice on study day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology

Statistics:

No statistical analysis was required.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.73 mg/L air (analytical)

Based on:

test mat.

Remarks:

gravimetric aerosol concentration

Exp. duration:

4 h

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Chromorrhinorrhea and breathing difficulty was observed in all six animals immediately following exposure and five of six at one hour thereafter. Chromodacryorrhea was observed in five of six animals immediately following exposure and at one hour thereaf

Body weight:

A decrease in mean body weight of approximately 9.5% in males and 1% in females was observed between study day 1 (exposure) and study day 2. From study day 2 to the end of the observation period (day 15), body weight increased gradually in all animals.

Gross pathology:

Red lungs with red spots were observed in one male and red spots were also present in the lungs of two females. These findings were considered to be related to test item exposure. No macroscopic changes were observed in any of the rest of the organs/tissues.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No. 1272/2008.

Conclusions:

The LC50 of dizinc pyrophosphate was greater than 4.73 mg/L air (gravimetric aerosol concentration), and based on the GHS classification criteria, can be considered unclassified.