Neodymium di(2-ethylhexyl) phosphate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 28 May 2007 to 13 December 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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

slight high body weight of one animal on day 1 (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.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

see higher

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

see higher

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/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 animals had a mean body weight of 314 ± 5 g for the males and 217 ± 9 g for the females
- Fasting period before study: no
- Housing: during the treatment period, the animals were housed individually in polycarbonate cages with stainless steel lid (35.5 cm x 23.5 cm x 19.3 cm)
- Diet: free access to SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water: 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 12 June 2007 (treatment) to 26 June 2007 (necropsy of the last animal)

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area
- % coverage: approximately 10% of the total body surface of the animals
- Type of wrap if used: gauze pad held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing: yes (using a dry cotton pad)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- For solids, paste formed: yes (the hydrophilic gauze pad was pre-moistened with 2 mL of purified water)

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

five males and five females

Control animals:

not required

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. From day 2, any local cutaneous reaction was recorded.
> 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:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic clinical signs were observed during the study. Crusts were noted in one female from day 11 until day 15 (end of the observation period).

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:

Dermal LD50 of neodymium tris(di-2-ethylhexylphosphate) is higher than 2000 mg/kg bw for male and female rats.

Executive summary:

In an acute dermal toxicity study according to OECD TG 402, EC B.3, OPPTS 870.1200 and GLP (CIT report No.33192 TAR, 2007), scored as validity 1 according to Klimisch criteria, a group of 8-week old Sprague-Dawley rats (5/sex) were applied a single dermal dose of undiluted neodymium tris(di-2-ethylhexylphosphate) at the dose of 2000 mg/kg bw (limit test) under a semi-occlusive dressing applied for 24 hours. The animals were 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. Local tolerance was also observed from Day 2.

No deaths and no systemic clinical signs were observed during the study.

Crusts were noted in one female from day 11 until day 15 (end of the observation period).

When compared to historical control animals, a slightly lower body weight gain was noted in 1/5 females between day 8 and day 15. The overall body weight gain of the other animals was not affected by treatment with the test item.

No apparent abnormalities were observed at necropsy in any animal.

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

   

No classification for acute dermal toxicity is warranted based on the absence of mortality up to a limit dose level, 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.