Neodymium trihydroxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 August 2016 to 24 August 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2011

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Neodymium trihydroxide

EC Number:

240-514-4

EC Name:

Neodymium trihydroxide

Cas Number:

16469-17-3

Molecular formula:

H3NdO3

IUPAC Name:

neodymium trihydroxide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): neodymium trihydroxide
- Physical state: solid
- Appearance: clear blue powder (purple under UV light)

Specific details on test material used for the study:

- correction factor: a correction factor (1.17) was applied

Test animals

Species:

rat

Strain:

other: Crl:(WI) Wistar

Sex:

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, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks
- Weight at study initiation: 203-220 g
- Fasting period before study: Overnight prior to treatment. Food but not water was withheld. Food was returned 3 h after treatment.
- Housing: Group caging (3 animals/cage) in Type II polypropylene/polycarbonate cage type. “Lignocel 3/4-S Hygienic Animal Bedding” and “Arbocel crinklets natural” nest building material were available during the study.
- Diet (e.g. ad libitum): ssnill(R) SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" (batch number: 278 5652, expiry date: 30 November 2016), ad libitum
- Water (e.g. ad libitum): Tap water from the municipal supply, as for human consumption from a 500 mL bottle, ad libitum.
- Acclimation period: 18-19 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ºC
- Humidity (%): 30-70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 h/12 h, lighting period from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES:
- From: 2016-08-09 To: 2016-08-23 (females no. 1957, 1958, 1959)
- From: 2016-08-10 To: 2016-08-24 (females no. 1960, 1961, 1962)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The selection of the vehicle was based on trial formulations with the test item.
- Lot/batch no. (if required): 7170914

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: Test item was freshly formulated on the day of administration. To limit the impact, the formulations were used within 4 hours after adding the vehicle to the test item and the test item preparation was performed with approved procedures and documented in detail. The formulation was homogenised to visually acceptable levels and was stirred up to finishing the treatment to ensure sufficient homogeneity.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. In the absence of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose. The limit dose (= starting dose level) for this study was 2000 mg/kg bw. Initially, three female animals were treated with 2000 mg/kg bw of the test item. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines (OECD 423, Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 animals, 3 animals/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Clinical signs: Animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4 and 6 hours after the treatment and once each day in the morning for 14 consecutive days thereafter. Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Body weight: The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: Yes, all animals were subjected to a necropsy and a macroscopic examination. The animals were exsanguinated after verification of narcosis following an injection of pentobarbital sodium. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross macroscopic changes were recorded for each animal.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Neodymium trihydroxide did not cause mortality at a dose level of 2000 mg/kg bw.

Clinical signs:

other: All animals were symptom free during the study.

Gross pathology:

There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Other findings:

No data

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the acute oral LD50 value of the test item neodymium trihydroxide was found to be above 2000 mg/kg bw in female Crl:WI rats. The study result triggers the following classification/labelling:
- Regulation (EC) No 1272/2008 (CLP): “No category”
- GHS (rev. 6) 2015: “Category 5 or Unclassified”