Neodymium di(2-ethylhexyl) phosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1 September 2006 to 20 april 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: the study was performed according to internationally recognised guidelines and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

the temperature recorded was sometimes outside of the target ranges, but this minor deviation was not considered to have compromised the validity or integrity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

see higher

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

see higher

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: on the day of treatment, the animals were approximately 8 weeks old
- Weight at study initiation: on the day of treatment, the mean body weight was 199 ± 9 g
- Fasting period before study: approximately 18 hours before dosing (but free access to water)
- Housing: polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals during the acclimation period and three rats during the treatment period.
- Diet: free access to SsniffR/M-H pelleted diet
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 30 to 70%
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: from 13 September 2006 (first treatment) to 18 October 2006 (necropsy of the last animal)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 or 200 g/L
- Amount of vehicle: 10 mL
- Justification for choice of vehicle: no data
- Lot/batch no.: 015K0115 (Sigma, Saint-Quentin-Fallavier, France)

MAXIMUM DOSE VOLUME APPLIED: 10 mL

DOSAGE PREPARATION: the test item was ground to a fine powder using a mortar and pestle, then was prepared at the chosen concentrations in the vehicle

CLASS METHOD
- Rationale for the selection of the starting dose: based on information provided by the sponsor

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 females at 300 mg/kg bw
2x3 females at 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical signs and mortality: frequently during the hours following administration of the test item, at least once a day thereafter
> Body weight: the animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: At 300 mg/kg, piloerection and dyspnea were noted in all the animals one hour after treatment. Piloerection was still observed 2 hours after treatment. No other clinical signs were noted thereafter, until the end of the observation period. At 2000 mg/kg,

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of neodymium tris(di-2-ethylhexylphosphate) is > 2000 mg/kg bw (with no mortality at this dose level).

Executive summary:

In an acute oral toxicity study according to OECD 423, EC B.1 tris, US/EPA/OPPTS 870.1100 and GLP (CIT report 32229 TAR, 2007), scored as validity 1 according to Klimisch criteria, groups of fasted 8-week old Sprague-Dawley rats were given a single oral dose of neodymium tris(di-2-ethylhexylphosphate) in corn oil at the dose of 300 and 2000 mg/kg bw (3 and 2x3 females, respectively) and observed for 14 days. Clinical signs and mortality were checked frequently during the hours following administration of the test substance, and at least once a day thereafter. Body weight was measured just before administration of the test substance on day 1 and then on days 8 and 15.

 

No mortality occurred during the study.

At 300 mg/kg, piloerection and dyspnea were noted in all the animals one hour after treatment. Piloerection was still observed 2 hours after treatment. At 2000 mg/kg, piloerection was noted in 3/6 females 4 hours after treatment only.

No other clinical signs were noted thereafter, until the end of the observation period.

A slightly lower body weight gain was noted between day 8 and day 15 in 1/6 females treated at the dose-level of 2000 mg/kg, when compared to historical control animals. The overall body weight gain of the other animals treated at the dose-level of 300 or 2000 mg/kg was not affected by treatment with the test item.

At necropsy, no apparent abnormalities were observed in any animal.

Under the experimental conditions, the oral LD50 of the test item neodymium tris(di-2-ethylhexylphosphate) was higher than 2000 mg/kg in rats.

No classification for acute oral toxicity is warranted based on the absence of mortality up to 2000 mg/kg bw, according to the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.

This study is classified as acceptable, as it is performed according to OECD guideline and GLP.