Dihexyl ether

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 July 2018 - 2 August 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

2017

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

d.d. 03 Aug 2018

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dihexyl ether

EC Number:

203-987-8

EC Name:

Dihexyl ether

Cas Number:

112-58-3

Molecular formula:

C12H26O

IUPAC Name:

1-(hexyloxy)hexane

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Sulzfeld, Germany
- Females, nulliparous and non-pregnant: yes
- Age at study initiation: ~9 weeks old
- Weight at study initiation: Between 204 g and 241 g
- Fasting period before study: No
- Housing: Individual and group caging
- Cage type: Type II. polypropylene/polycarbonate
- Bedding: Lignocel 3/4-S Hygienic Animal Bedding (produced by J. Rettenmaier & Söhne GmbH+Co.KG, Germany) was available to animals during the study. The quality of the bedding was guaranteed by the supplier. Details of bedding quality are archived with the raw data.
- Nesting: Nest building material Arbocel Crinklets natural (produced by J. Rettenmaier & Söhne GmbH+Co.KG, Germany) was available to animals during the study. The quality of the nest building material was guaranteed by the supplier. Details of nest building material quality are archived with the raw data.
- Enrichment: Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet: Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany, ad libitum
- Water: tap water from the municipal supply, ad libitum
- Acclimation period: 12 or 14 days
- Microbiological status: SPF at arrival

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1–25.3
- Humidity (%): 40–79
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 17 JUL 2018 To: 02 AUG 2018

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10% of total body surface
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats to cover the test item. Entire truk of the animal was wrapped with semi occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing: water at body temperature
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Pre-study: 1 female at 2000 mg/kg bw
Main study: 2 females at 2000 mg/kg bw

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were performed at periodic intervals on the day of dosing and once daily thereafter; body weights were recorded on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured.

Clinical signs:

other: There were no systemic clinical signs noted in any animal throughout the study. No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period.

Gross pathology:

There was no evidence of any gross macroscopic changes at a dose level of 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

In an acute dermal toxicity study according to OECD TG 402 and in accordance with GLP principles the LD50 of the test item Di-n-hexyl ether was found to be greater than 2000 mg/kg body weight in female Crl:WI rats.
According to the GHS criteria, Di-n-hexyl ether can be ranked as "Category 5 or Unclassified" for acute dermal exposure.

Executive summary:

An acute dermal toxicity study was performed with the test item Di-n-hexyl ether in three female Wistar rats, in compliance with OECD Guideline No. 402.

The test item was applied as a single dermal 24-hour exposure of 2000 mg/kg followed by a 14-day observation period.

Test item did not cause mortality and no systemic clinical signs were noted in any animal throughout the study. No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period. There was no treatment related effects on body weight or body weight gain during the observation period. Body weights were within the range commonly recorded for this strain and age and there was no evidence of any macroscopic changes.

The acute dermal median lethal dose (LD50) of the test item Di-n-hexyl ether was found to be greater than 2000 mg/kg body weight in female Crl:WI rats.