Reaction mass of 5,8,11,14-Tetraoxaoctadecane and 5,8,11,14,17-Pentaoxaheneicosane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2011-06-28 to 2011-07-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientifically well performed study; Guideline study; GLP study Rational for the read-across: the registration substance and the read-across supporting substances belong to homologues of butyl-O-(CH2CH2-O)n-butyl

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-butoxyethyl) ether

EC Number:

204-001-9

EC Name:

Bis(2-butoxyethyl) ether

Cas Number:

112-73-2

Molecular formula:

C12H26O3

IUPAC Name:

1,1'-[oxybis(ethane-2,1-diyloxy)]dibutane

Constituent 2

Reference substance name:

DEGDBE

IUPAC Name:

DEGDBE

Test material form:

gas under pressure: refrigerated liquefied gas

Details on test material:

Name: Diethyleneglycoldibutylether
Chemical Name: Bis(2-butoxyethyl)ether
CAS No.: 112-73-2
Physical State: liquid
pH: 6.5-7.5 (25°C, 100 g/L i-propanol/water 4:1)
Colour: colourless
Storage Conditions: at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Full barrier in an air-conditioned room
- Temperature: 22  3 °C
- Relative humidity: 55  10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1130)
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 040311)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days)

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test item was applied at a single dose, uniformly over an area which was approximately 10% of the total body surface.
The test item was held in contact with the skin by a dressing throughout a 24-hour period. The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

Duration of exposure:

The test item was held in contact with the skin by a dressing throughout a 24-hour period.

Doses:

The test item was applied at a single dose of 2000 mg/kg body weight to each animal.

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not required

Details on study design:

The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure period the residual test item was removed using aqua ad injectionem (Berlin Chemie, lot no. 0195A191, expiry date: 04/2013). All animals were observed for 14 days after dosing. The animals were weighed on day 1 (prior to the application) and on days 8 and 15. A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. All animals were subjected to gross necropsy. All gross pathological changes were recorded.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

> 2 000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality was observed during the observation period

Clinical signs:

other: The test item showed no signs of acute dermal toxicity but minor signs of dermal irritation after a single dose application.

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal

Other findings:

Eschar was observed in 3 of 5 male and all female animals. Desquamation was observed in 4 of 5 female animals and scratches were observed in 1 of 5 female animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal toxicity of the registration substance is derived based on the read-across approach. Diethylenglycoldibuthylether(DEGDBE) was tested for its dermal acute toxicity in rats according to the OECD Guideline 402. At dose level of 2000 mg/kg bw no mortality and no signs of toxicity were observed. The dermal LD50 was determined to be > 2000 mg. Likewise, low acute dermal toxicity is to be assigned for the registration substance. No classification is to be assigned for the registration substance.

Executive summary:

The acute dermal toxicity of the registration substance is based on the read-across approach, using diethylenglycoldibutylether (DEGDBE) as read-across supporting substance.

DEGDBE was investigated for its dermal toxicity according to the OECD Guideline 402. Five male and female rats each were treated with DEGDBE at doses of 2000 mg/kg bw. No significant effect was observed.

DEGDBE belongs to the homologues of butyl-O-(CH2CH2O)n-butyl with n =2, whereas the main components of the registration substance correspond to the homologues with n = 2,3,4. No toxicity difference is expected based on the basic concept of "chain length category" for the homologues and the observed acute dermal toxicity of DEGDBE is considered to be representative for all components of the registration substance. A low acute dermal toxicity can be reasonably assigned for the registration substance. No classification is to be assigned for the registration substance.