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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 November 2020 to 09 December 2020

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 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

09 October 2017

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

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
- Purity, including information on contaminants, isomers, etc.: 99.90%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature (15-25°C) in darkness, under nitrogen atmosphere
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage: The test item was administered as supplied and no vehicle was used
- Stability in the medium, i.e. sensitivity of the test material to hydrolysis and/or photolysis: Determination of the homogeneity, stability and purity of the test item not undertaken as part of this study.


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): no
- Preliminary purification step (if any): no

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST albino rats

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat: Rats are the preferred species of choice as they are historically used for safety evaluation studies and are specified in the appropriate test guidelines. As there were no data to indicate males were likely to be more sensitive to the test item, the testing was performed in females only.
- Source: Envigo RMS (UK) Ltd
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately eight to twelve weeks of age prior to dosing (Day 1)
- Weight at study initiation: 187 to 207 g
- Fasting period before study: no
- Housing: housed in groups of one or two rats
- Diet: ad libitum; Teklad 2014C Diet
- Water: ad libitum; Potable water taken from the public supply
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24C
- Humidity (%): 40 to 70%
- Air changes (per hr): animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05 November 2020 To: 09 December 2020

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10%
- Type of wrap if used: porous gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with warm water (30 to 40°C)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.1 ml/kg
- Constant volume or concentration used: 2 ml/kg for the first animal and 2.1 ml/kg for the 3 other animals

Duration of exposure:

24 hours

Doses:

- 2000 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages of rats were checked at least twice daily for any mortalities; The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15
- Necropsy of survivors performed: yes
- Clinical signs including body weight: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). Additional observations were performed as necessary when evident toxicity was observed. The nature and severity, where appropriate, of any clinical signs and the time were recorded at each observation.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 200 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths in the study.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

There was a low body weight gain for female number 92, from Day 1 to Day 8, however, this animal achieved a satisfactory body weight gain between Day 8 and Day 15. A low body weight gain was noted for one female (number 93) from Day 8 to Day 15. All other animals were considered to have achieved satisfactory body weight gains throughout the study.

Gross pathology:

Macroscopic examination at study termination on Day 15 revealed pallor of the liver in two females (number 92 and 93) in the main study. No abnormalities were revealed in any other animal at the macroscopic examination at this time.

Other findings:

A bandage reaction was observed from Day 8 until the end of the study for animal number 91, dosed in the sighting study at a dose level of 1906 mg/kg. There were no other dermal reactions throughout the study.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute median lethal dermal dose (LD50) to rats of 4,8-Dimethyl-2,5,7,10-tetraoxaundecane was demonstrated to be greater than 2000 mg/kg body weight.
4,8-Dimethyl-2,5,7,10-tetraoxaundecane is included in Category 5/Unclassified, according to the Globally Harmonised System (GHS).

Executive summary:

The purpose of this study was to assess the toxic potential of 4,8-Dimethyl-2,5,7,10-tetraoxaundecane, an industrial chemical, following a single dermal dose in the rat.
Female rats received a single dermal dose of the test item at the following dose levels:
Sighting investigation: 1906 mg/kg body weight
Main study: Based on the results of the sighting investigations a further three females were dosed at 2000 mg/kg body weight.
During the study, clinical conditions, dermal reactions, body weight and macropathology investigations were undertaken.
Results
There were no deaths in the study.
Urine staining in the lower ventral area was observed for two females in the main study dosed at 2000 mg/kg. This sign was first noted on Day 2 and recovery of this sign was complete by Day 3. No clinical signs were observed in the sighting study female dosed at 1906 or other main study animal dosed at 2000 mg/kg.
A bandage reaction was observed from Day 8 until the end of the study for animal number 91, dosed in the sighting study at a dose level of 1906 mg/kg. There were no other dermal reactions throughout the study.
There was a low body weight gain for female number 92, from Day 1 to Day 8, however, this animal achieved a satisfactory body weight gain between Day 8 and Day 15. A low body weight gain was noted for one female (number 93) from Day 8 to Day 15. All other animals were considered to have achieved satisfactory body weight gains throughout the study.
Macroscopic examination at study termination on Day 15 revealed pallor of the liver in two females (number 92 and 93) in the main study. No abnormalities were revealed in any other animal at the macroscopic examination at this time
Conclusion
The acute median lethal dermal dose (LD50) to rats of 4,8-Dimethyl-2,5,7,10-tetraoxaundecane was demonstrated to be greater than 2000 mg/kg body weight.
4,8-Dimethyl-2,5,7,10-tetraoxaundecane is included in Category 5/Unclassified, according to the Globally Harmonised System (GHS).