Neodymium trifluoride

Endpoint summary

Description of key information

ACUTE TOXICITY: VIA THE ORAL ROUTE
All three studies report an acute oral LD50 in the rat of >5000 mg/kg bodyweight. 
ACUTE TOXICITY: VIA INHALATION ROUTE
In accordance with Section 2 of Annex XI of Regulation (EC) No. 1907/2006, the acute toxicity by inhalation study, listed under point 8.5.2 of Annex VIII of the same Regulation, had been waived as it is not technically feasible to conduct the study. The sticky nature of the test substance made it impossible to generate the dust atmosphere required for the study.
ACUTE TOXICITY: VIA DERMAL ROUTE
The dermal LD0 in the rat was >2000 mg/kg.
ACUTE TOXICITY: OTHER ROUTES
the LD0 of the test material to the rat is >5000 mg/kg when administered via the intraperitoneal route.

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:

not reported

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Sprague-Dawley OFA (IOPS)
- Age at study initiation: 6 - 7 weeks
- Weight at study initiation (prior to fasting): 160 - 200 g (males); 140 - 180 g (females)
- Fasting period before study: yes (17 hours)
- Housing: 2 or 5 animals in plastic cages (365 x 225 x 180 mm) containing a sterilised and vacuum-cleaned sawdust litter
- Food consumption: ad libitum
- Water consumption: ad libitum
- Acclimation period: data not available

ENVIRONMENTAL CONDITIONS:
- Temperature: 22 ± 1.5 °C
- Humidity: 55 ± 15 %
- Air changes: 10 per hour
- Photoperiod: data not available

Route of administration:

oral: gavage

Vehicle:

other: 10 % aqueous dispersion of gum arabic

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 g test item / 100 mL
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> behaviour and mortality: 1, 2 and 4 h, and on days 1, 2, 4, 7 and 14 after treatment
> weighing: one day before treatment, and on days 0, 7 and 14 after treatment
- Necropsy of survivors performed: yes

Preliminary study:

Mortality checks were performed at 1, 2, 4 hours, and then on days 1, 2, 4, 7 and 14.
No mortality was observed.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in rats dosed with 0 or 5000 mg/kg bw.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

No gross abnormalities were observed at necropsy.

Other findings:

No mortality in preliminary test

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD0 (males and females) was >5000 mg/kg bw and therefore the test material is not classified for acute oral toxicity based on the results of this study in accordance with EU criteria.

Executive summary:

An acute oral toxicity limit test was conducted to assess the test material in accordance with the standardised guidelines OECD 401 and EU Method B.1.

Groups of fasted, 6 - 7 week old Sprague-Dawley rats (5 per sex) were given a single oral dose of the test material in a 10 % aqueous solution of gum arabic at a dose of 5000 mg/kg bw and observed for 14 days. 5 animals were dosed with the vehicle only.

No mortality and no clinical signs were observed during the study. No gross abnormalities were observed at necropsy.

The oral LD0 (males and females) was >5000 mg/kg bw and therefore the test material is not classified for acute oral toxicity based on the results of this study in accordance with EU criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Two supporting studies are available. The first was conducted in accordance with the standardised FHSA guideline 16 CFR 1500.3. It was well reported and adhered to sound scientific principles. It was awarded a reliability score of 1 in accordance with the criteria of Klimisch (1997).
The second supporting study was conducted in accordance with a method which was broadly equivalent to the standardised FHSA guideline 16 CFR 1500.3. It adhered to sound scientific principles, however was not fully reported and as such was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not reported

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Sprague-Dawley OFA (IOPS)
- Age at study initiation: 6 - 7 weeks
- Weight at study initiation (prior to fasting): 160 - 200 g (males); 140 - 180 g (females)
- Fasting period before study: no
- Housing: animals were individually housed in plastic cages (375 x 170 x 150 mm) containing a sterilised and vacuum-cleaned sawdust litter
- Food consumption: ad libitum
- Water consumption: ad libitum
- Acclimation period: data not available

ENVIRONMENTAL CONDITIONS:
- Temperature: 22 ± 1.5 °C
- Humidity: 55 ± 15 %
- Air changes: 10 per hour
- Photoperiod: data not available

Type of coverage:

occlusive

Vehicle:

other: 10 % aqueous dispersion of gum arabic

Details on dermal exposure:

-The test material was applied to the shaved laterodorsal area of the back. It was administered in the 10 % aqueous dispersion of gum Arabic at a dose volume of 5 mL/kg and a concentration of 40 g/mL.
-The test material was covered by foil and secured with tape.
-After 24 hours, the dressing was removed and the treated area rinsed with warm water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> behaviour and mortality: after application, then 1, 2 and 4 hours; daily from day 1 to day 14
> weighing: one day before treatment, and on days 0, 7 and 14 after treatment
>cutaneous condition was noted from day 1 onwards
- Necropsy of survivors performed: yes

Preliminary study:

Mortality checks were performed at 1, 2, 4 hours, and then on days 1, 2, 4, 7 and 14.
No mortality was observed.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No abnormalities, erythema or oedema were observed.

Gross pathology:

No gross abnormalities were observed at necropsy.

Other findings:

No mortalities in the preliminary test.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD0 (males and females) was >2000 mg/kg bw and therefore the test material is not classified based on the results of this study in accordance with EU criteria.

Executive summary:

An acute dermal toxicity limit test was conducted to assess the test material in accordance with the standardised guidelines OECD 402 and EU Method B.3.

Groups of 6 - 7 week old Sprague-Dawley rats (5 per sex) were exposed to a single 2000 mg/kg dermal dose of the test material in a 10 % aqueous solution of gum arabic. The test material was applied to the shaved laterodorsal area and the site covered in foil secured with tape. After 24 hours, the dressing was removed and the site rinsed with water. Animals were observed for 14 days.

No mortality and no clinical signs were observed during the study. No gross abnormalities were observed at necropsy.

The dermal LD0 (males and females) was >2000 mg/kg and therefore the test material is not classified for acute dermal toxicity based on the results of this study in accordance with EU criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The key study was conducted in line with GLP and in accordance with the standardised guidelines OECD 402 and EU method B.3. It was well reported and adhered to sound scientific principles. It was awarded a reliability score of 1 in accordance with the criteria of Klimisch (1997).

Additional information

Acute toxicity: via the oral route

The key study is an acute oral toxicity limit test conducted in accordance with the standardised guidelines OECD 401 and EU Method B.1.

Groups of fasted, 6 - 7 week old Sprague-Dawley rats (5 per sex) were given a single oral dose of the test material in a 10 % aqueous solution of gum arabic at a dose of 5000 mg/kg bw and observed for 14 days. 5 animals were dosed with the vehicle only.

No mortality and no clinical signs were observed during the study. No gross abnormalities were observed at necropsy.

The oral LD0 (males and females) was >5000 mg/kg bw and therefore the test material is not classified for acute oral toxicity based on the results of this study in accordance with EU criteria.

 

The first supporting study is an acute oral toxicity limit test conducted in accordance with FHSA guideline 16 CFR 1500.3.

Groups of fasted Sprague-Dawley rats (5 per sex) were given a single oral dose of the test material in certified feed at a dose of 5000 mg/kg bw and observed for 14 days.

The oral LD50 (males and females) was > 5000 mg/kg bw and therefore the substance is not classified for acute oral toxicity according to EU criteria on the basis of this study.

 

The second supporting study is an acute oral toxicity limit test was conducted broadly in accordance with FHSA guideline 16 CFR 1500.3.

Groups of fasted Sprague-Dawley rats (5 per sex) were given a single oral dose of the test material in distilled water at a dose of 5000 mg/kg as a 50 % w/w solution and observed for 14 days.

The oral LD50 (males and females) was > 5000 mg/kg bw and therefore the material is not classified for acute oral toxicity according to EU criteria on the basis of this study.

 

Acute toxicity: via the inhalation route

In the supporting study, an attempt was made to assess the toxicity potential of the test material via the inhalation route in accordance with the standardised guideline OECD 436.

Due to the nature of the test material, the study was not carried out due to a lack of success at creating a suitable exposure atmosphere for animals. It was not possible to generate an atmosphere of the test material that was suitable for an acute inhalation study, either as a dust or liquid aerosol.

It may have been possible to generate an atmosphere by dissolving the test material in a suitable solvent, but this was ultimately considered to be unrepresentative of the hazard presented by the test material and so was not pursued further.

In view of the physical nature of the test material and its apparent low volatility, it is considered unlikely to represent a significant hazard by the inhalation route in its original form.

 

Acute toxicity: via the dermal route

An acute dermal toxicity limit test was conducted to assess the test material in accordance with the standardised guidelines OECD 402 and EU Method B.3.

Groups of 6 - 7 week old Sprague-Dawley rats (5 per sex) were exposed to a single 2000 mg/kg dermal dose of the test material in a 10 % aqueous solution of gum arabic. The test material was applied to the shaved laterodorsal area and the site covered in foil secured with tape. After 24 hours, the dressing was removed and the site rinsed with water. Animals were observed for 14 days.

No mortality and no clinical signs were observed during the study. No gross abnormalities were observed at necropsy.

The dermal LD0 (males and females) was >2000 mg/kg and therefore the test material is not classified for acute dermal toxicity based on the results of this study in accordance with EU criteria.

 

Acute toxicity: via other routes

A supporting study is provided in which the toxicity of the test material when administered by the intraperitoneal route was investigated.

No guideline was available for this type of study, however it was carried out in accordance with sound scientific methodology and the principles of good laboratory practice. As such it was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997). 

10 fasted Sprague-Dawley rats (5 per sex) were administered the test material via the intraperitoneal route in a 10 % aqueous dispersion of gum arabic. The animals were observed for 14 days before being euthanised and subject to necropsy.

There was no mortality seen and no abnormal effects on bodyweight were reported. Clinical signs observed were hollow flanks in some animals, while others were observed to have bloated bellies.

During the postmortem examinations, the abdominal and chest cavities were opened and the organs inspected. It was noted that the test material was present with granulomas.

Under the conditions of this study, the LD0 of the test material to the Sprague-Dawley rat is >5000 mg/kg when administered via the intraperitoneal route in a 10 % aqueous dispersion of gum arabic.

Justification for selection of acute toxicity – oral endpoint
The key study was conducted in line with GLP and in accordance with the standardised guidelines OECD 401 and EU Method B.1. It was well reported and adhered to sound scientific principles. It was awarded a reliability score of 1 in accordance with the criteria of Klimisch (1997).

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the test material does not require classification for acute toxicity.