2-({[4-({bis[4-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)phenoxy](sulfanylidene)-$l^{5}-phosphanyl}oxy)phenyl]carbamoyl}oxy)ethyl prop-2-enoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-({[4-({bis[4-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)phenoxy](sulfanylidene)-λ⁵-phosphanyl}oxy)phenyl]carbamoyl}oxy)ethyl prop-2-enoate

EC Number:

918-919-9

Cas Number:

1072454-85-3

Molecular formula:

C36H36N3O15PS

IUPAC Name:

2-({[4-({bis[4-({[2-(prop-2-enoyloxy)ethoxy]carbonyl}amino)phenoxy](sulfanylidene)-λ⁵-phosphanyl}oxy)phenyl]carbamoyl}oxy)ethyl prop-2-enoate

additive 1

Reference substance name:

Ethyl acetate

EC Number:

205-500-4

EC Name:

Ethyl acetate

Cas Number:

141-78-6

Molecular formula:

C4H8O2

IUPAC Name:

ethyl ethanoate

Test material form:

liquid

Specific details on test material used for the study:

solution in ethyl acetate (about 40 % solid content)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 165-185 g
- Housing: 3 animals per cage
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 5 °C
- Air changes (per hr): > 10 per hour
- Photoperiod (hrs dark / hrs light): 12h rhythm

IN-LIFE DATES: From: To: 28 OCT 2016 to 17 NOV 2016

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

application volume 10 mL/kg bw
The analyses of the dosage formulations revealed that the test item was stable in the concentration range used beyond the defined period of use. Homogeneity and stability testing of the test item in the administration vehicle prior to study start showed a homogeneous distribution and stability for at least 2 days. Accuracy of concentrations was checked during the in-life phase.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: twice daily or daily
- body weights: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy

Statistics:

not applicable

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

other: No clinical signs; in one animal increased salivation was observed; it remains unclear if this finding was treatment-related

Gross pathology:

no findings

Other findings:

none

Any other information on results incl. tables

Dose (mg/kg bw)	Toxicological results	clinical sign	Onset of mortality
(1st) 2000	0 / 1/ 3	salivation	---
(2nd) 2000	0 / 0/ 3	---	---

Toxicological results:

number of dead animals / number of animals with signs after treatment / number of animals treated

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

The acute oral LD50 in rats is determined with >2000 mg/kg bw based on the results of a limit dose study performed according to OECD TG 423. The test dose of 2000 mg/kg was well tolerated, without effects on body weight development and gross pathological findings.