Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-09-20 to 2011-11-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD guideline No. 423 and EU method B.1tris in a GLP certified testing facility.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Sponsor’s identification: 400160
Batch No: KL-11-039
Composition: UVCB; 2-Ethylhexyl esters of dimerised fatty acids, C18-unsaturated
Purity: 100% (GPC)
Date received: 12 August 2011
Production date: 24 March 2011
Expiry date: 24 March 2016
Container: glass flask (n=1)
Quantity : 77.53 g (container + contents)
Form: liquid
Colour: yellow
Storage: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Animals:
6 Sprague Dawley rats (SPF Caw) originated from Elevage JANVIER (53940 Le Genest St Isle – France), were used after an acclimatization period of at least 5 d. At the beginning of the study, the animals of the treated group weighed between 182 g and 201 g and were 8 weeks old. They were identified prior to inclusion in the test by means of numbered rings on the edges of their ears.

Group treated (2000 mg/kg):
3 female rats Rf8133 to Rf8135 (Step 1)
3 female rats Rf8157 to Rf8159 (Step 2)

Housing:
Healthy female rats were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry. The temperature and relative humidity of the main test were controlled to remain within target ranges of 19 to 25°C and 30 to 70%, respectively. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give 12 h continuous light (07.00 to 19.00) and 12 h darkness.

Food and drink:
Drinking water (tap-water from public distribution system) and foodstuff (M20, SDS) were supplied freely. Food was removed at d 1 and then redistributed 4 h after the test item administration.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
In the first and second steps of the study, 2000 mg of the test item was administered as supplied by gavage under a volume of 2.22 mL/kg b.w. (according to the density calculated) using a suitable syringe graduated fitted with an oesophageal metal canula.
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
6
Control animals:
yes
Details on study design:
A control study with 3 animals receiving the control item destilled water was performed in July 2011 to assess the comportment of the strain of rat used at this laboratory in this environment and to give additional historical data.
The test item BYK-400160 was administered to a group of 6 female Sprague Dawley rats at the single dose of 2000 mg/kg body weight. Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. The animals were weighed on day d 0 (just before administering the test item) then on d 2, 7 and 14. Weight changes were calculated and recorded. On d 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels. Macroscopic observations were entered on individual autopsy sheets. Those organs likely to be modified in cases of acute toxicity were examined.
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs related to the administration of the test item were observed.
Body weight:
The body weight evolution of the animals remained normal throughout the study.
Gross pathology:
The macroscopical examination of the animals at the end of the study did not reveal treatment related change.
Other findings:
No other findings were observed.

Any other information on results incl. tables

Body weight evolution – group treated

Dose: 2000 mg/kg body weight

D 0: 20 September 2011 (step 1) & 21 September 2011 (step 2)

 

Table 1 Body weight and weight gain in grams

FEMALES

 d 0               d 2           d2-d 0

 d 7            d7-d 0           d14          d14-d 0

Rf8133

Rf8134

Rf8135

182              194               12

191              207               16

 201              216               15

222               40               225               43

 235               44               245               54

 245               44               248               47

Rf8157

Rf8158

Rf8159

201              222               21

200              220               20

190              206               16

249               48               263               62

242               42               243               43

233               43               241               51

 MEAN

Standard deviation

 194.2           210.8            16.7

   7.8             10.6             3.3

 237.7            43.5            244.2            50.0

   9.8              2.7              12.2              7.3

 

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of 400160 is higher than 2000 mg/kg body weight by oral route in the rat.
In accordance with the OECD guideline No. 423, the LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat. According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the EEC Directives 67/548, 2001/59 and 99/45, the test item 400160 does not have to be classified. No symbol or risk phrase is required.
In accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures, the test item does not have to be classified. No signal word or hazard statement is required.
Executive summary:

In an acute oral toxicity study two groups of 8 week old female Sprague Dawley rats (SPF Caw) (n=6) were given a single oral dose of 400160 at doses of 2000 mg/kg b.w. and observed for 14 days.

No mortality or any other clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study. The microscopical examination of the animals at the end of the study did not reveal treatment related changes.

The test was performed as limit test.

Oral LD50 (females) >2000 mg/kg b.w.

400160 is of low toxicity based on the LD50 in female rats.