Neodymium trinitrate

Endpoint summary

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

Study period:

27 March 2020 to 7 May 2020

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

Qualifier:

according to guideline

Guideline:

other: • EC No 440/2008 Part B. Acute Oral Toxicity, Acute Toxic Class Method, May 2008.

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: • Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF), November 2000, including the most recent revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: NDNC-191202-BZ
- Expiration date of the lot/batch: 12 December 2020

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under storage conditions: Assumed to be stable
- Stability under test conditions: Assumed to be stable
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium: 100 g/L at 20°C in water


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure.
- Final dilution of a dissolved solid, stock liquid or gel: Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing.
No adjustment was made for specific gravity of the vehicle. No correction was made for the purity/composition of the test item.

Species:

rat

Strain:

Wistar

Remarks:

Wistar Han

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 147 to 177 g
- Fasting period before study: Yes
- Housing: Polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized wooden fibers as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. 3 animals per cage
- Diet (e.g. ad libitum): Yes. Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): yes. Municipal tap-water was freely available to each animal via water bottles.
- Acclimation period: 5 days
- Method of randomisation in assigning animals to test and control groups : Animals were assigned to the study at the discretion of the coordinating biotechnician, with all animals within ± 20% of the sex mean body weights.
Before the initiation of dosing, a health inspection was performed and any assigned animal considered unsuitable for use in the study were replaced by alternate animals obtained from the same shipment and maintained under the same environmental conditions.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.
- Photoperiod (hrs dark / hrs light): A 12 hour light/12 hour dark cycle was maintained

IN-LIFE DATES: From: 27 March 2020 To: 7 May 2020

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 and 2000 mg/kg bw
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure.

MAXIMUM DOSE VOLUME APPLIED:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 300 mg/kg bw. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Clinical signs including body weight : yes
- Other examinations performed: clinical signs, body weight, histopathology

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, two females were found dead on Day 2 post-treatment. No further mortality occurred.

Clinical signs:

other: At 300 mg/kg, two animals showed erect fur on Day 1. No clinical signs were noted for the other animal. At 2000 mg/kg, labored or shallow breathing was noted for the animals between Days 1 and 3. One animal showed abnormal breathing sounds on Days 1-3, 6

Gross pathology:

An abnormality of the stomach (irregular glandular surface) was found in one of the animals that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the other animal that died during the study and of the surviving animals at termination did not reveal any abnormalities.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The oral LD50 value of Neodymium Trinitrate in Wistar Han rats was >2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2500 mg/kg body weight.
Based on these results, according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017), Neodymium Trinitrate should be classified as: Category 5 for acute toxicity by the oral route and according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), Neodymium Trinitrate does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Executive summary:

The objective of this study was to assess the toxicity of the test item when administered in a single dose to female rats at one or more defined dosages. Furthermore, the results of the study allowed the test item to be ranked according to most classification systems, currently in use. This study should provide a rational basis for risk assessment in man.

The study was carried out in compliance with the guidelines described in OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method";  EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method"; EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"; JMAFF Guidelines (2000), including the most recent revisions.

Initially, Neodymium Trinitrate was administered by oral gavage to three female Wistar Han rats at 300 mg/kg body weight. In a stepwise procedure two additional groups of three females were dosed at 2000 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15). At 2000 mg/kg, two females were found dead on Day 2 post-treatment. No further mortality occurred. At 300 mg/kg, two animals showed erected fur on Day 1. No clinical signs were noted for the other animal. At 2000 mg/kg, labored or shallow breathing was noted for the animals between Days 1 and 3. One animal showed abnormal breathing sounds on Days 1-3, 6 and 7. Closed eyes (partly or completely) and uncoordinated movements (slight or moderate) were noted for all animals on Day 1. Hunched posture and erected fur was observed in all animals between Days 1 and 4. Furthermore, all animals showed decreased activity between Days 1 and 3.

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

An abnormality of the stomach (irregular glandular surface) was found in one of the animals that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the other animal that died during the study and of the surviving animals at termination did not reveal any abnormalities.

The oral LD50value of Neodymium Trinitrate in Wistar Han rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2500 mg/kg body weight.

Based on these results, according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017), Neodymium Trinitrate should be classified as: may be harmful if swallowed (Category 5) for acute toxicity by the oral route and according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), Neodymium Trinitrate does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Klimisch 1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The oral LD50 value of Neodymium Trinitrate in Wistar Han rats was >2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2500 mg/kg body weight.

Based on these results, according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017), Neodymium Trinitrate should be classified as: Category 5 for acute toxicity by the oral route and according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), Neodymium Trinitrate does not have to be classified and has no obligatory labelling requirement for oral toxicity.

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