Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021
Report date:
2021

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
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Reaction Product of 1,1,1-Trimethylol propane triacrylate with aziridine and 1-cyclooctyl-1,4-diazocane and 4-hydroxy-4-methylpentan-2-one
Molecular formula:
C6H12N2 - C47H77O16N4
IUPAC Name:
Reaction Product of 1,1,1-Trimethylol propane triacrylate with aziridine and 1-cyclooctyl-1,4-diazocane and 4-hydroxy-4-methylpentan-2-one
Test material form:
liquid
Details on test material:
Name of test item: Emuldur 3643
Test item No.: 19/0071-2
Batch identification: 27771924U0
Purity: 100 % (UVCB*, for details see analytical characterization No.20L00150) *Substances of unknown or variable composition, complex reaction products.
Homogeneity: The test item was homogeneous by visual inspection.
Storage stability: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Expiry date: July 15, 2021
Storage conditions: Ambient (RT)
Physical state / color: Liquid / colorless to yellowish, clear

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: Young adult animals (female animals approx. 9-11 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing, Makrolon cage, type III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Acclimatization period of at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The homogeneity of the test item during administration was ensured by stirring with a magnetic stirrer.
Administration volume (mL/kg bw): 1.84
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
EXPERIMENTAL PROCEDURE
Route of administration: Single oral administration by gavage.
Fasting period: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
Time of day of administration: In the morning
Observation period: 14 days
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
Mortality: A check for any dead or moribund animals was made at least once each workday; these records are archived by Bioassay.
Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.
Histology: No histological examinations were performed.
Statistics:
Not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the first test group. In the second test group, one animal was found dead at hour 5 after administration.
Clinical signs:
other: In the first 2000 mg/kg bw. test group, impaired general state was noticed in all animals at hour 1 and persisted in one of these animals until study day one. In two animals poor general state was seen at hour 2, followed by impaired general state from ho
Gross pathology:
The following macroscopic pathologic findings were observed in two surviving animals of the first 2000 mg/kg bw test group on the last day of observation (day 14): conglomerates in the stomach.
The following macroscopic pathologic findings were noted in the single animal that died in the second 2000 mg/kg bw. test group: Dark red, spotted discoloration of all lung lobes, red, spotted discoloration of the liver, dark red discoloration of the glandular stomach and small intestine, congestion in the kidneys
There were no macroscopic pathological findings in the other three animals sacrificed at the end of the observation period (first 2000mg/kg test group: 1 female; second 2000 mg/kg bw. test group: 2 females).

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of Emuldur 3643 after oral administration was assessed to be greater than 2000 mg/kg bw in rats.