4,8-Dimethyl-2,5,7,10-tetraoxaundecane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 4 February 2021 to 16 March 2021

Reliability:

1 (reliable without restriction)

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)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4,8-dimethyl-2,5,7,10-tetraoxaundecane

Cas Number:

59039-15-5

Molecular formula:

C9H20O4

IUPAC Name:

4,8-dimethyl-2,5,7,10-tetraoxaundecane

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: Lambiotte & Cie - 2101081010R
- Purity, including information on contaminants, isomers, etc.: 99.96%

Test animals

Species:

rat

Strain:

Sprague-Dawley

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: Young adult animals (approximately 8-10 weeks old)
- Weight at study initiation: 145 to 192 g
- Fasting period before study: no
- Housing: group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.
- Method of randomisation in assigning animals to test and control groups: Animals were assigned to the study at the discretion of the coordinating biotechnician, with all animals within ± 20% of the sex mean body weights. Animals in poor health or at extremes of body weight range were not assigned to the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 21°C
- Humidity (%): 40 to 59%
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle was maintained

IN-LIFE DATES: From: 15 February 2021 To: 16 March 2021

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item, 4,8-Dimethyl-2,5,7,10-tetraoxaundecane, was administered as received. Amber glassware was used for the preparations of formulations.

The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / spec.gravity or density (g/mL) * purity correction factor.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing. Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter.
- Necropsy of survivors performed: yes

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 mortality occurred.

Clinical signs:

irregular respiration

lethargy (hypoactivity)

observations of tremors

other: hunched posture, erected fur, partly closed eyes

Body weight:

other body weight observations

Remarks:

The body weight gain shown by the 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:

Enlargement of the heart was found in two animals at macroscopic post-mortem examination.
Macroscopic post-mortem examination of the other animals did not reveal any abnormalities

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The oral LD50 value of 4,8-Dimethyl-2,5,7,10-tetraoxaundecane in Sprague Dawley rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 5000 mg/kg body weight.
Based on the results and taking into account the severe clinical signs seen, according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), 4,8-Dimethyl-2,5,7,10-tetraoxaundecane should be classified as: may be harmful if swallowed (Category 5) for acute toxicity by the oral route.
According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), 4,8-Dimethyl-2,5,7,10-tetraoxaundecane does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Executive summary:

The objective of this study was to assess the toxicity of the test item when administered in a single dose to female rats at one or more defined dosages. Furthermore, the results of the study allowed the test item to be ranked according to most classification systems, currently in use. This study should provide a rational basis for risk assessment in man.
The study was carried out in compliance with the guidelines described in:
• OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method".
• EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method".
• EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity".
• JMAFF Guidelines (2000), including the most recent revisions.
4,8-Dimethyl-2,5,7,10-tetraoxaundecane was administered by oral gavage to two consecutive groups of three female Sprague Dawley rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).
No mortality occurred.
Shallow breathing, hunched posture, erected fur, partly closed eyes, and decreased activity were noted for all animals between Days 1 and 4. In addition, some of the animals also showed slight tremors and/or prostrate posture on Day 1 and one animal also showed abnormal breathing sounds on Day 1.
The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Enlargement of the heart was found in two animals at macroscopic post-mortem examination.
Macroscopic post-mortem examination of the other animals did not reveal any abnormalities.
The oral LD50 value of 4,8-Dimethyl-2,5,7,10-tetraoxaundecane in Sprague Dawley rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 5000 mg/kg body weight.
Based on these results:
• According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), 4,8-Dimethyl-2,5,7,10-tetraoxaundecane should be classified as: may be harmful if swallowed (Category 5) for acute toxicity by the oral route.
• According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), 4,8-Dimethyl-2,5,7,10-tetraoxaundecane does not have to be classified and has no obligatory labelling requirement for oral toxicity.