Magnesium diniobate

Endpoint summary

Description of key information

Acute toxicity studies with magnesium diniobate are not available, thus the acute toxicity will be addressed with existing data on the dissociation products.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2008-10-03

Deviations:

yes

Remarks:

purity and stability not stated; observation period last 72 hours only; test item preparation missing; number of dead animals not reported; gross pathology not performed; sex and age of animals missing

GLP compliance:

not specified

Remarks:

not specified in the publication

Test type:

up-and-down procedure

Limit test:

no

Specific details on test material used for the study:

not specified

Species:

mouse

Strain:

Swiss

Remarks:

albino

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight: 20 - 35 grams
- Housing: housed in polypropylene cages
- Diet: standard pellet diet (Hindustan Lever, Bangalore, India)
- Water (ad libitum)

ENVIRONMENTAL CONDITIONS
- Temperature: 22 - 24°C
- Humidity: 75 %
- Photoperiod (hrs dark / hrs light): 14/10

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

The first animal receives a dose one step below the assumed estimate of the LD50. If the animal survives, the second animal receives a higher dose. If the first animal dies, the second animal receives a lower dose (Chen et al. (2006))*.

*Reference:
- Chen Z, Meng H, Xing G et al. Acute toxicological effects of copper NPs in vivo. Toxicol. Lett. 2006; 163: 109 - 120

Doses:

1000 to 5000 mg/kg bw

No. of animals per sex per dose:

10 mice

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 72 hours
- General examination: after administration of the test item, animals were examined daily for their survival, evident behavior or motor impairments and effect on their body weight.
- Behavioral changes: drowsiness, hyperactivity, moving of tail, scratching of body, loss of hair, texture of hair (smooth, or rough) etc were observed.

Statistics:

LD50 was calculated using probit analysis (Randhawa (1944); Miller & Tainter (1944))*.

*References:
- Randhawa MA. Calculation of LD50 values from the method of Miller and Tainter, 1944. J Ayub Med Coll Abbottabad 2009; 21(3): 184-5
- Miller LC, Tainter ML. Estimation of the LD50 and its error by means of logarithmic probit graph paper. Proc Soc Exp Biol Med. 1944; 57:261–264.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 954 mg/kg bw

Based on:

test mat.

Mortality:

not specified

Clinical signs:

The mice exposed to the test item showed hyperactivity, moving of tail but the hair remained smooth.

Body weight:

not specified

Gross pathology:

not specified

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (mice): 3954 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, magnesium oxide is not acutely toxic via the oral route.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-08-11 to 2009-08-26

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)

Version / remarks:

2001-12-17

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008-05-30

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2009-04-06

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature

Species:

rat

Strain:

other: Crl:WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 10 weeks old
- Weight at study initiation: 162 - 181 g
- Fasting period before study: prior to the administration food was withheld for 16 to 19 hours (access to water was permitted) and food was provided again approx. 4 hours post dosing.
- Housing: kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (ad libitum): Altromin 1324 maintenance diet for rats and mice
- Water (ad libitum): tap water, sulfur acidified to a pH value of approx. 2.8
- Acclimation period: 13 or 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10 %
- Air changes: 10 x/hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: deionised water

Details on oral exposure:

DOSAGE PREPARATION:
The test item was suspended in deionised water.

VEHICLE
- Justification for choice of vehicle: vehicle was chosen due to its non-toxic characteristics.
- Lot no.: 09/07/14

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female rats (3 females/step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were weighed on day 1 (prior to administration) and on day 8 and on day 15. A clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose) as well as once daily thereafter until the end of the observation period.
- Necropsy of survivors performed: yes, all animals were subjected to gross necropsy.

Statistics:

not applicable

Preliminary study:

none

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

No signs of toxicity were observed.

Body weight:

None of the animals showed weight loss during the observation period .

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia, no special gross pathological changes were recorded for any animal.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Signs of acute oral toxicity are not expected for magnesium diniobate, since the two constituents magnesium and niobium have not shown signs of acute oral toxicity in experimental testing (both LD50 > 2000 mg/kg bw). Under the assumption that the constituents of magnesium diniobate show their toxicological profile individually upon dissolution, the acute oral (systemic) toxicity of magnesium diniobate can be estimated using the equation given in Regulation (EC) 1272/2008, Annex I, Section 3.1.3.6.1; the oral LD50 for magnesium diniobate is > 2000mg/kg.

A study for acute toxicity via inhalation or the dermal route was not conducted with magnesium diniobate since it can safely be assumed to have a low potential for human inhalation hazard and a low potential for dermal absorption during handling or application as assessed in the corresponding derogation statements. Thus, acute toxic effects are not likely to occur during manufacture and handling of that substance.

Justification for classification or non-classification

The available information indicates that magnesium diniobate is not acutely toxic or harmful. The calculated oral LD50 for magnesium diniobate is > 2000mg/kg. Therefore, classification of magnesium diniobate for acute toxicity is not required according to Regulation (EC) 1272/2008.

The classification criteria according to Regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure are not met since adverse health effects, including reversible and irreversible, were not observed immediately or delayed after exposure.