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Description of key information

The acute oral toxicity of the registration substance was investigated according to the OECD Guideline 401. No significant toxicity was found at dose of 2000 mg/kg bw. 
The acute dermal toxicity of the registration substance was derived based on the read-across approach. No concern could be soundly assigned for the registration substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
testing starting date 1993-01-06; testing finishing date 1993-01-20; reporting date 1993-02-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically well performed study; Guideline study; GLP study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% (weight/volume)
- Amount of vehicle (if gavage): 10 mg/kg


Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Unspecific toxicity observed on day of application. No further effects were observed.

On day of application the treated animals responded with unspecific intoxication signs. These included increased respiration rate, irregualr respiration, stupor, coat bristling, flanks drawn in, stilted gait, ataxic gait, prone position, squatting posture, clonic convulsions, trembling, fissure narros, narcosis, no corneal reflex, reduced pawreflex to pincing, no pawreflex to pinching, no lacing reaction and creased spontaneous activity. All these effects disappeared within 24 hours. The treated animals exhibited normal body weight development in the observation period of 14 days.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No classification is assigned for the registration substance for the endpoint acute oral toxicity.
Executive summary:

The acute oral toxicity of the registration substance was investigated according to the OECD Guideline 401. 5 male and 5 female rats were treated with triethyleneglycoldibutylether (representative material for the registration substance) at dose of 2000 mg/kg bw via gavage. No mortality occured. On the application day unspecific toxicity signs were observed, which disappeared within 24 hours. The treated animals exhibited normal body weight development in the observation period of 14 days. The acute oral toxicity of the registration substance is found to be of no concern.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
One valid oral acute toxicity study

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
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
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)
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.
Sex:
male
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000
Quality of whole database:
One valid acute dermal toxicity study:

Additional information

Acute oral toxicity

The acute oral toxicity of the registration substance was investigated according to the OECD Guideline 401. 5 male and 5 female rats were treated with triethyleneglycoldibutylether (representative material for the registration substance) at dose of 2000 mg/kg bw via gavage. No mortality occured. On the application day unspecific toxicity signs were observed, which disappeared within 24 hours. The treated animals exhibited normal body weight development in the observation period of 14 days. The acute oral toxicity of the registration substance is found to be of no concern.

 

Acute dermal toxicity

The acute dermal toxicity of the registration substance is 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.

 

Justification for the use of diethylenglycoldibutylether (DEGDBE) as read-across supporting substance

DEGDBE belongs to the homologues of butyl-O-(CH2CH2O)n-butyl with n =2, whereas the main components of the registration substance (PolyEGDBE) correspond to the homologues with n = 2,3,4.

Read-across supporting substance

Diethylene glycol dibutyl ether (DEGDBE)**

CAS 112-73-2

Butyl-O- (CH2CH2-O)2-Butyl

Registration substance

(Target chemical)

Polyethylene glycol dibutyl ether (PolyEGDBE)***

CAS 31885-97-9

Butyl-O- (CH2CH2-O-)n-Butyl

n = 2,3,4

The only difference for the registration substance and DEGDBE being the number of ethylenglycol unit in the center of the molecule, the basic concept of "chain length category" can be applied. A comparable toxicity profile is expected.

In addition, the available data for the endpoint repeated dose toxicity are strongly supporting the proposed approach, in that the both substances induced hemolysis and liver effect (OECD 422 study on the registration substance, 28 -day toxicity study on DEGDBE; both studies provided in corresponding endpoint study records), whereas DEGDBE was found to be more potent than the registration substance.

Taking account that DEGDBE is of lower molecular size than the registration substance and that DEGDBE is of less potency than the registration substance after prolonged oral exposure, the registration substance is not likely to exhibit enhanced acute dermal toxicity than DEGDBE.

In conclusion, the data of DEGDBE can be soundly used for the hazard assessment of the registration substance with respect to the acute dermal toxicity.


Justification for selection of acute toxicity – oral endpoint
Scientifically well performed study; Guideline study; GLP study

Justification for selection of acute toxicity – dermal endpoint
Applied read-across is scientifically valid; Scientifically well performed study; Guideline study; GLP study

Justification for classification or non-classification

The acute oral toxicity of the registration substance was investigated according to the OECD Guideline 401. No significant toxicity was found at dose of 2000 mg/kg bw.

The acute dermal toxicity of the registration substance was derived based on the read-across approach. No concern could be soundly assigned for the registration substance.

No classification should be assigned for the registration substance.