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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018
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 guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[[1-(chloromethyl)-2-[[4-(oxiran-2-ylmethoxymethyl)cyclohexyl]methoxy]ethoxy]methyl]oxirane
Molecular formula:
C17H29ClO5
IUPAC Name:
2-[[1-(chloromethyl)-2-[[4-(oxiran-2-ylmethoxymethyl)cyclohexyl]methoxy]ethoxy]methyl]oxirane
Constituent 2
Chemical structure
Reference substance name:
cis-1,4-bis[(2,3-epoxypropoxy)methyl]cyclohexane
Cas Number:
1197197-64-0
Molecular formula:
C14H26O4
IUPAC Name:
cis-1,4-bis[(2,3-epoxypropoxy)methyl]cyclohexane
Constituent 3
Chemical structure
Reference substance name:
trans-1,4-bis[(2,3-epoxypropoxy)methyl]cyclohexane
Cas Number:
158307-92-7
Molecular formula:
C14H26O4
IUPAC Name:
trans-1,4-bis[(2,3-epoxypropoxy)methyl]cyclohexane
impurity 1
Chemical structure
Reference substance name:
[4-(oxiran-2-ylmethoxymethyl)cyclohexyl]methanol
Molecular formula:
C11H20O3
IUPAC Name:
[4-(oxiran-2-ylmethoxymethyl)cyclohexyl]methanol
impurity 2
Chemical structure
Reference substance name:
[4-[[3-chloro-2-(oxiran-2-ylmethoxy)propoxy]methyl]cyclohexyl]methanol
Molecular formula:
C14H25ClO4
IUPAC Name:
[4-[[3-chloro-2-(oxiran-2-ylmethoxy)propoxy]methyl]cyclohexyl]methanol
impurity 3
Chemical structure
Reference substance name:
2-[[3-chloro-2-[[4-[[3-chloro-2-(oxiran-2-ylmethoxy)propoxy]methyl]cyclohexyl]methoxy]propoxy]methyl]oxirane
Molecular formula:
C20H34Cl2O6
IUPAC Name:
2-[[3-chloro-2-[[4-[[3-chloro-2-(oxiran-2-ylmethoxy)propoxy]methyl]cyclohexyl]methoxy]propoxy]methyl]oxirane
impurity 4
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M Company, Batch TX7E5501
- Expiration date of the lot/batch: 26 May, 2022
- Purity test date: 05 December, 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test article was adminstered neat.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 141-209 grams
- Fasting period before study: Yes, overnight
- Housing: On arrival and following assignment to the study, animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. The room in which the animals were kept were documented in the study records. Animals were separated during designated procedures/activities. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures. The feed was analyzed by the supplier for nutritional components and environmental contaminants. Results of the analysis were provided by the supplier and are on file at the Test Facility. It is considered that there were no known contaminants in the feed that would interfere with the objectives of the study.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles. Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility. It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 26-50
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Jaunuary, 2018 To: 16 February, 2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: None

MAXIMUM DOSE VOLUME APPLIED: No data
Doses:
The first group was treated at a dose level of 2000 mg/kg. Based on the results, two additional groups were dosed at 300 mg/kg.
No. of animals per sex per dose:
3 females per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible
findings. Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored. Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: All animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg, two animals were found dead on Day 1.
At 300 mg/kg, no mortality occurred.
Clinical signs:
Lethargy, flat posture, hunched posture, piloerection and/or ptosis were noted for the animals that were found dead on Day 1. Hunched posture and piloerection were noted for the surviving animals on Days 1 and/or 2.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
Abnormalities of the gastrointestinal tract (gelatinous contents) and liver (reddish discoloration) were found for the animals that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the remaining animals did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of the study, the female rat oral LD50 of the test article is 1000 mg/kg body weight.
Executive summary:

The acute oral lethality potential of the test article was examined in female Wistar rats. The study was conducted according to OECD 423 (2001) in compliance with OECD GLP regulations. Rats (3 females) received 2000 mg/kg test article via oral gavage (neat). In a stepwise procedure two additional groups of 3 female rats were dosed at 300 mg/kg. Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings. Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored. Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing. At 2000 mg/kg two animals were found dead on Day 1. At 300 mg/kg, no mortality occurred. Lethargy, flat posture, hunched posture, piloerection and/or ptosis were noted for the animals that were found dead on Day 1. Hunched posture and piloerection were noted for the surviving animals on Days 1 and/or 2. Abnormalities of the gastrointestinal tract (gelatinous contents) and liver (reddish discoloration) were found for the animals that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the remaining animals did not reveal any abnormalities. Based on the results of the study, the female rat oral LD50 of the test article is 1000 mg/kg body weight.

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