Registration Dossier

Administrative data

Description of key information

DEGDBE is of low acute oral and dermal toxicity. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 900 mg/kg bw
Quality of whole database:
The available database is considered to be sufficiently robust to demonstrate low acute oral toxicity.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-06-28 to 2011-07-13
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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:
The test item showed no signs of acute dermal toxicity but minor signs of dermal irritation after a single dose application.

Body weight:
A slight weight loss was recorded for 2 of 5 female animals during the first week, but all of the female animals showed weight gain during the second week. The toxicological relevance of this finding cannot clearly be concluded.
The male animals showed weight gain during the first and the second week of the observation.
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:
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. No classification is warranted.
Executive summary:

On the basis of the test results given below and in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC as well as inAnnex I of Regulation (EC) 1272/2008, the substance should be not classified

On the basis of the test results given below and in conformity with the criteria given in inOECD-GHS (Globally Harmonized System of Classification and Labelling of Chemicals)[8], the substance should be classified into category 5.

LD50:                                                        > 2000 mg /kg bw

Species/strain:                                         WISTAR Crl: WI(Han) rats

Vehicle (moistening):                               no vehicle used

Number of animals:                                  5 male and 5 female

Duration of exposure:                             24 hours

Method: OECD 402, EC 440/2008, OPPTS 870.1200

Sex

Dose
(mg/kg bw)

Number
of Animals

Number
of Intercurrent Deaths

male

2000

5

0

female

2000

5

0

Signs of toxicity related to dose level used, time of onset and duration:

No treatment-related effects were observed.

Effect on organs (related to dose level):

No treatment-related effects were observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The data base comprises study in rats and study in rabbits, with varing quality. The study results are consistent, therefore considered to be sufficiently robust.

Additional information

No valid acute oral toxicity study is available for DEGDBE. However one secondary source, reporting 3900 mg/kg bw as LD50 for rats and one 8 -day repeated dose toxicity study in pregnant mice in which the LD10 is given as 2000 mg/kg bw. These informations are clearly demonstrating low acute oral toxicity.

The acute dermal toxicity was investigated according to the OECD Guideline 402. At dose level of 2000 mg/kg bw no mortality and no indiciation of toxicity was found.


Justification for selection of acute toxicity – oral endpoint
One acute toxicity study in rats and one repeated 8 day toxicity study in pregnant mice were used. These information are considered to be of equally adequate to derive the acute oral toxicity.

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

Justification for classification or non-classification

For the exposure routes oral and dermal, low toxicity potential after single application could be obviously demonstrated based on the available data. No classification is warranted for the endpoint acute oral and acute dermal toxicity. No data is available for the inhalation route.