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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
This study was conducted between 16 October 2017 and 13 November 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
EC No. 440/2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure

Test material

Constituent 1
Chemical structure
Reference substance name:
Xanthylium, 3,6-bis(diethylamino)-9-[2-(ethoxycarbonyl)phenyl]-, molybdatetungstatephosphate
EC Number:
215-414-9
EC Name:
Xanthylium, 3,6-bis(diethylamino)-9-[2-(ethoxycarbonyl)phenyl]-, molybdatetungstatephosphate
Cas Number:
1326-04-1
IUPAC Name:
Xanthylium, 3,6-bis(diethylamino)-9-[2-(ethoxycarbonyl)phenyl]-, molybdatetungstatephosphate
Test material form:
solid: nanoform
Details on test material:
Shape
Shape Category: spheroidal
Shape: spherical
Pure Shape:no
Typical Composition: ≤100%
range: >0; ≤100%

Particle size distribution & range
Shape Category: spheroidal
Percentile D10, typical value: 40nm
Percentile D10, range: ≥10; ≤60nm
Percentile D50, typical value: 60nm
Percentile D50, range: ≥40; ≤100nm
Percentile D90, typical value: 90nm
Percentile D90, range: ≥60; ≤150nm
Fraction in size range 1-100nm:≥50; ≤100%

Crystallinity
structure: Amorphous
Pure structure: Yes

Specific Surface Area
Typical specific surface area: ca. 40m2/g
Range: ≥10; ≤200m2/g
Skeletal Density: 2.1 g/cm3

Surface Functionalisation/treatment
surface treatment applied no

Specific details on test material used for the study:
Information as provided by the Sponsor.
Identification: Lumière Pink PTM 0245F
Batch Number: 280PE310516
CAS Number: 1326-04-1
EC Number: 215-414-9
Purity: UVCB (treat as 100%)
Appearance: dark magenta powder
Expiry Date: 01 July 2022
Storage Conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan™:WIST
Sex:
female
Details on test animals or test system and environmental conditions:
Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight of any previously dosed animals at the start of treatment.

Animal Care and Husbandry
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.

Test Item Preparation and Analysis
For the purpose of the study the test item was freshly prepared, as required, as a suspension in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.
The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
One animals was treated at a dose level of 300 mg/kg
A total of five animals were treated at a dose level of 2000 mg/kg
Control animals:
no
Details on study design:
Study Design
In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
A single animal was treated as follows:
Dose Level (mg/kg) Concentration (mg/mL) Dose Volume (mL/kg) Number of Rats
300 30 10 1

In the absence of toxicity a dose level of 300 mg/kg, an additional animal was treated as follows:
Dose Level (mg/kg) Concentration (mg/mL) Dose Volume (mL/kg) Number of Rats
2000 200 10 1

In the absence of mortality at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
Dose Level (mg/kg) Concentration (mg/mL) Dose Volume (mL/kg) Number of Rats
2000 200 10 4

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Data Evaluation
The test item was classified according to Annex 3 of the OECD Guidelines for Testing of Chemicals No. 420 "Acute Oral Toxicity - Fixed Dose Procedure" (adopted 17 December 2001).
Evaluation of data included identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of evident toxicity were described. Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on body weights and abnormalities noted at necropsy were also identified.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
There were no deaths at any dose level
Clinical signs:
300 mg/kg Dose Level
There were no signs of systemic toxicity noted. Red colored staining on the feces was noted two to six days post dosing.

2000 mg/kg Dose Level
There were no signs of systemic toxicity noted. Red colored staining of the feces and/or urine was noted in the cages of all animals up to six days after dosing. Red colored staining of the fur was noted in four animals one to two days after dosing.
Body weight:
All animals showed expected gains in body weight over the observation period. (See Tables 1 and 2)
Gross pathology:
No abnormalities were noted at necropsy at any dose level

Any other information on results incl. tables

Table 1 Individual Body Weights and Body Weight Changes - 300 mg/kg

Dose Level

(mg/kg)

Animal Number
and Sex

Body Weight (g) at Day

Body Weight Gain (g)
During Week

0

7

14

1

2

300

1-0 Female

158

170

188

12

18

Table 2 Individual Body Weights and Body Weight Changes -2000mg/kg

Dose Level

(mg/kg)

Animal Number
and Sex

Body Weight (g) at Day

Body Weight Gain (g) During Week

0

7

14

1

2

2000

2-0 Female

170

180

193

10

13

3-0 Female

182

190

199

8

9

3-1 Female

186

196

208

10

12

3-2 Female

170

181

190

11

9

3-3 Female

187

199

209

12

10

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Unclassified
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System  Unclassified).
Executive summary:

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Methods

Following a sighting test at dose levels of300 mg/kg and2000 mg/kg, a further group of four fasted females was given a single oral dose of test item, as asuspensioninarachis oil BP, at a dose level of2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality.  There were no deaths.

Clinical Observations.There were no signs of systemic toxicity. Red stained feces and/or red stained urine and fur were noted in all animals.

Body Weight  All animals showed expected gains in body weight.

Necropsy. No abnormalities were noted at necropsy.

Conclusion

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than2000 mg/kg body weight (Globally Harmonized Classification System-Unclassified).

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