Vanadate(1-), oxo[phosphato(3-)-.kappa.O]-, hydrogen, hydrate (2:2:1)

Endpoint summary

Description of key information

LC50, oral, rat > 50 < 300 mg/kg bw (BASF SE, 2017)

LC50, inhalation, rat = 3694 mg/m3 (BASF SE, 2018)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single, Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

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

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 5 ml/kg bw
- Justification for choice of vehicle: Good homogeneity in corn oil Ph.Eur.

Doses:

300, 50 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw: 3
50 mg/kg bw: 2 x 3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- Mortality: A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
No histological examinations were performed.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

In the 300 mg/kg bw test group two animals were found dead on study day 1, while one animal of this test group was sacrificed in a moribund state on study day 1. No mortality occurred in both 50 mg/kg bw test groups.

Clinical signs:

other: In all animals of the 300 mg/kg bw test group impaired general state was noted at hour 5, which progressed in one of these animals to poor general state on study day 1. Dyspnoea, piloerection, diarrhea and cowering position were noted in all animals at ho

Gross pathology:

The following macroscopic pathologic findings were observed in both animals that died or in the single animal which was sacrificed in a moribund state in the 300 mg/kg bw test group: Spotted discoloration of the liver and red discoloration of the small intestine in all animals, black discoloration of the stomach contents in two animals.
There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (50 mg/kg bw: 6 females).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

GLP guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 10 weeks
- Weight at study initiation: males: 219.4 - 243.4 g, females: 185.2 - 213.7 g
- Fasting period before study: no
- Housing: Single housing or up to 5 animals (caged in groups)
- Diet (e.g. ad libitum): Kliba laboratory diet, mouse/rat maintenance “GLP”, 12 mm pellets, Provimi Kliba SA, Kaiseraugst, Basel Switzerland, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%): 30 – 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.8 - 3.4 µm

Geometric standard deviation (GSD):

3.8 - 4

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1.078 and 4.271 mg/l

No. of animals per sex per dose:

5

Control animals:

yes

Statistics:

By the data the LC50 was calculated by Probit analysis for the male animals by means of a computer program.
The dose-response curve was fitted via the probit model on the log scale of the concentration. This curve was used for the estimation of the LC50.
Statistical analyses were performed using the SAS procedure Proc Probit.
If the estimation of the LC50 lies outside the experimental range or the slope is not significantly different from 0, no confidence limits are given.
For results of the type ”LC50 greater than”, ”LC50 approx.”, or ”LC50 smaller than”, the binomial test was used for the female animals for statistical evaluation. For the statistical analysis the Binomial-Test was performed.
The calculation of the particle size distribution was carried out in the inhalation laboratory on the basis of mathematical methods for evaluating particle measurements.

Sex:

male

Dose descriptor:

LC50

Effect level:

3.694 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

> 4.271 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Test group 1 (1.078 mg/L):
No lethality was observed in male and female animals during the study period of 14 days.
Test group 2 (4.271 mg/L):
Four of the five male animals and one of the five females died or were sacrificed in a moribund state after exposure on study day 2, 3 or on study day 5 during the post-exposure observation period.

Clinical signs:

other: Test group 1 (1.078 mg/L) Male animals Female animals Fur, substance-contaminated d0 – d1 d0 – d1 Fur, urine stained - d2 – d4 Hunched posture d0 – d1 d0 – d1 Nose, substance like encrusted d0 – d1 d0 – d4 Respiration, intermittent h1 –

Body weight:

Test group 1 (1.078 mg/L)
The mean body weights of the animals decreased on the first post-exposure observation day but increased thereafter.

Test group 2 (4.271 mg/L)
The mean body weights of the surviving animals decreased on the first post-exposure observation days and increased thereafter.

Gross pathology:

Animals that died or were sacrificed in a moribund state during the study period
Findings test group 2
Number of animals 4 males + 1 female
Organs without particular findings 1 male
Lung (pulmo sinister, right cranial lobe):
red discoloration 1 male
Lung: dark-red discoloration 2 males + 1 female
Intestine: watery light-brown abnormal content 2 males + 1 female
Fur: light-brown smeared anogenital region 2 males + 1 female
Fur: test-item contaminated in head region 2 males + 1 female

Necropsy of the animals at termination of the post exposure periods
Findings test group 1 test group 2
Number of animals 5 males + 5 females 1 male + 4 females
Organs without particular findings 5 males + 5 females -
Lung:
few white - yellow foci - 1 male + 4 females

Other findings:

Histopathological findings
Animal No.:
75 79
Larynx
Level I (base of epiglottis)
Epithelial alteration
• slight x
Lungs
Inflammation, interstitial, mf.
• slight x
• moderate x
Histiocytosis, alveolar
• moderate x
Nasal cavity
Level III
Necrosis, multifocal
• slight x
Degeneration/regeneration, mf.
• slight x
Level IV
Necrosis, multifocal
• slight x
Degeneration/regeneration, mf.
• minimal x
Except for the epithelial alteration in the larynx, all findings in the lungs and nasal cavity were
considered adverse.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

3 694 mg/m³ air

Quality of whole database:

GLP guideline study

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

oral:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 300 and 50 mg/kg bw of the test item Vanadate(1-), oxo[phosphato(3-)-.kappa.O]-, hydrogen, hydrate (2:1) (preparations in corn oil Ph.Eur.) were administered by gavage to three test groups of three fasted Wistar rats each (300 mg/kg bw in 3 females and 50 mg/kg bw in 6 females) (BASF SE, 2017).

The test substance-related clinical observations were recorded in both test groups. Macroscopic pathological findings in the animals that died or that was sacrificed moribund: spotted discoloration of the liver in all animals, black discoloration of the stomach contents in two animals and red discoloration of the small intestine in all animals. No macroscopic pathological findings were observed in any animal sacrificed at the end of the observation period. The body weights of the surviving animals increased within the normal range throughout the study period with one exception. The body weight of one animal of the second administration group of the 50 mg/kg bw dose group slightly decreased during the first observation week but this animal gained weight normally during the second week.

The acute oral LD50 was calculated to be LD50, oral, rat > 50 < 300 mg/kg bw

inhaltion:

To determine the acute inhalation toxicity (single 4-hour exposure, nose only) of Vanadate(1-), oxo[phosphato(3-)-.kappa.O]-, hydrogen, hydrate (2:1) as a dust, a study was performed in male and female Wistar rats according to OECD-Guideline method 403 (BASF SE, 2018). The test was run with actual measured concentrations of 1.078 mg/L and 4.271 mg/L (analytical concentration). Cascade impactor measurements resulted in particle size distributions with mass median aerodynamic diameters (MMADs) between 1.8 and 3.4 μm, which are well within the respirable range.

No lethality was observed in male and female animals exposed to 1.078 mg/L. Four of five males and one of the females died or were sacrificed in a moribund state at 4.271 mg/L. Lethality was observed after exposure on study day 2, 3 or on study day 5. Clinical signs of toxicity were observed in all test groups. Histopathological examination revealed in the lungs an interstitial inflammation, with additional histiocytosis in the animal sacrificed after 14 days after exposure. In the nasal cavity at level II and IV, the olfactory and transitional epithelium showed multifocal necrosis in the animal sacrificed 5 days after exposure and multifocal degeneration/regeneration was noted in the olfactory epithelium in the animal sacrificed 14 days after exposure. These changes were considered adverse.

Under the current study conditions, the LC50 value was 3.694 mg/L (calculated based on analytical concentration) in male Wistar rats after a 4-hour inhalation exposure to the dust aerosol of Vanadate(1-), oxo[phosphato(3-)-.kappa.O]-, hydrogen, hydrate (2:1). The LC50 for female rats was > 4.271 mg/L (calculated based on analytical concentration) after a 4-hour inhalation exposure to the dust aerosol of Vanadate(1-), oxo[phosphato(3-)-.kappa.O]-, hydrogen, hydrate (2:1).

Justification for classification or non-classification

Based on the available data, Vanadate(1-), oxo[phosphato(3-)-.kappa.O]-, hydrogen, hydrate (2:1) will be classified in accordance with regulation (EC) 1272/2008 as acute toxic category 3 (H301) after oral administration and as acute toxic category 4 (H332) after inhalation.