Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
This study was conducted between 19 July 2017 and 07 August 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
PV1:2 read-across justification to PR81:5 for IUCLID

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have the same type of toxicological effects based on common underlying mechanisms (ECHA, 2015b). All substances have the same organic structural group (colorant) with different compositions of the inorganic group (metallic salt). Read-across is in this case based on the hypothesis that source and target substances have similar toxicological properties because they degrade to the similar chemical substances (ECHA, 2015c). This prediction is supported by physicochemical and toxicological data on the substances.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Name Source Substance Target Substance
IUPAC name Reaction product of 9-(2-carboxyphenyl)-3,6-bis(diethylamino)xanthylium Reaction product of ethyl 2-[3-(ethylamino)-6-ethylimino-2,7-dimethylxanthen-9-yl]
chloride with silicomolybdic acid benzoate with silicomolybdic acid
CAS No 62973-79-9 63022-06-0
EC No 263-778-2 263-793-4
Molecular weight range ≥ 3700 ≤ 8200 ≥ 3700 ≤ 8200
Molecular formula (C28H31N2O3)x.2SiO2.(MoO3)y C28H31N2O3)x.2SiO2.(MoO3)y
x = 6-10 x = 6-10
y = 7-25 y = 7-25


Structural formula Structures are given in the document attached in the section below

Both substances are UVCB’s and so purity is considered to be 100% 
3. ANALOGUE APPROACH JUSTIFICATION
The target substance CAS 62973-79-9 is an organometallic multi-constituent substance. The source substance CAS 63022-06-0 have the same organic constituent (see table above) as the target substance consisting of a basic 3,6-bis(diethylamino)xanthylium structure which has been has additional methyl groups at positions 2,7 (PR81:5, only)and a carboxyphenyl group at position 9 which, for PR81:% only, has an ethyl substitution at position 2.. The inorganic Part B is the same between source and target substances, consisting of the elements O, Mo, P and W in different compositions. These differences are expected to behave very similar. The target and source substances are thus considered suitable for the analogue approach based on structural similarity.
4. DATA MATRIX
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
EC No. 440/2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Specific details on test material used for the study:
Information as provided by the Sponsor.
Identification: Lumière Pink S.M. 8135N
Batch: 021340
CAS Number: 63022-06-0
EC Number: 263-793-4
Purity: ≥90% UVCB (treat as 100%)
Physical state/Appearance: red powder
Expiry Date: 01 July 2022
Storage Conditions: room temperature in the dark
Species:
rat
Strain:
Wistar
Remarks:
RccHan™:WIST
Sex:
female
Details on test animals 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
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.
No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Study Design
Using available information on the toxicity of the test item, 2000 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
2000 200 10 1

In the absence of toxicity 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 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
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.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Red colored stained feces and urine was noted 1 and 2 days after dosing in the cage of the four additional treated animals. Red stained fur of the four additional treated animals was noted 1 to 7 days after dosing.
Body weight:
All animals showed expected gains in body weight over the observation period. (See Table 1)
Gross pathology:
No abnormalities were noted at necropsy

Table 1 Individual Body Weights and Body Weight Changes

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

1-0 Female

160

183

198

23

15

2-0 Female

157

170

180

13

10

2-1 Female

166

180

194

14

14

2-2 Female

157

173

189

16

16

2-3 Female

160

174

180

14

6

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 acute oral median lethal dose (LD50) in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight from the acute oral toxicity of source study XG44CC. As explained in the justification for type of information, the difference in molecular structure between the target and source are unlikely to lead to any significant differences in the acute oral toxicity value.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification