Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-06-05 to 2008-08-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Name: Me-3K4A2
Chemical name: Benzoic acid, 4-[4-[(1-oxo-2- propenyl)oxy]butoxy]-, 2-methyl-1,4-phenylene ester
Colour: beige
Physical state: powder
Stability in solution
or suspension: probably stable
Special procedures for dose preparation: prepare freshly
Storage: at room temperature, protected from light

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
HsdRccHan : WIST rats (Full-Barrier), Sex: females, non-pregnant, nulliparous.
Step 1: Body weight at the commencement of the study: 176 – 191 g;
Step 2: Body weight at the commencement of the study: 160 – 164 g.
Three female animals were used for each step.
The animals were derived from a controlled full barrier maintained breeding
system (SPF).
Source: Harlan Winkelmann GmbH, D-33178 Borchen.
The animals were barrier maintained (semi-barrier) in an air conditioned
room
- Temperature: 22 ± 3 °C
- Rel. humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Feeding ad libitum, Altromin 1324 maintenance diet for rats and mice
- Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- The animals were kept in Macrolon cages on Altromin saw fiber bedding
- Certificates of food, water and bedding are filed at BSL Bioservice
- Adequate acclimatization period (at least 5 days)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
For animal no.1 of the first step, 1 g of the test item was diluted with the
vehicle ad 5 mL to gain a dosis of 2000 mg/kg body weight at a volume of 10 mL/kg body weight. For animals no. 2 and 3 of the first step, 2 g of the
test item were diluted with the vehicle ad 10 mL to gain a dosis of 2000 mg/kg body weight at a volume of 10 mL/kg body weight.
For animals no. 1, 2 and 3 of the second step, 2 g of the test item were diluted with the vehicle ad 10 mL to gain a dosis of 2000 mg/kg body weight at a volume of 10 mL/kg body weight.
Doses:
The test item was administered at a volume of 10 mL/kg body weight.
In the first step the test item was given at a dose of 2000 mg/kg body weight
to a group of 3 female rats. No compound-related mortality was found in
any animals of step 1. Based on the results of the first step and in accordance
with the acute toxic class regime the second step was performed with the
same dose in the same manner to a further groups of 3 female rats.
According to the acute toxic class method regime no further testing was
required since no compound-related mortality was found in any animals of
step 2.
No. of animals per sex per dose:
3 females per step
Control animals:
no
Details on study design:
A careful clinical examination was made several times on the day of dosing. Part of this were at least three observations within the first four hours post dose. Animals were observed once a day thereafter. 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. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
not applicable

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: none
Mortality:
No signs of toxicity related to dose level used, time of onset and duration were observed in any animal at any time.
Clinical signs:
No signs of toxicity related to dose level used, time of onset and duration were observed in any animal at any time.
Body weight:
Throughout the 14-days observation period no weight loss was recorded in any surviving animal. The weight gain was within the expected
range.
Gross pathology:
Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were
found in any animal of any step.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to GHS (Globally Harmonized Classification System) the test item Me-3K4A2 was not classified (LD50 cut-off: >5000 mg/kg body weight).
Executive summary:

The acute toxic class method was performed with the test item Me-3K4A2. In the first step the test item was given at a dose of 2000 mg/kg body weight to a group of 3 female rats (HsdRccHan : WIST) in a single exposure via oral gavage. Based on the results of the first step and in accordance with the acute toxic class regime the second step was performed with the same dose in the same manner to a further groups of 3 female rats (HsdRccHan : WIST). Following the acute toxic class regime of OECD 423 no further testing was required.

A careful clinical examination was made several times on the day of dosing. Part of this were at least three observations within the first four hours postdose. Animals were observed once a day thereafter. No signs of toxicity related to dose level used, time of onset and duration were observed in any animal at any time.

No treatment related effect was observed in any animal of any step. Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were found in any animal of any step. Throughout the 14-days observation period no weight loss was recorded in any surviving animal. The weight gain was within the expected

range.

Based on these results and according to OECD Guideline 423, a sufficient estimation of the acute oral toxicity of the test item is provided. Considering the reported data of this toxicity test it can be stated that the test item Me-3K4A2 showed acute oral toxic characteristics. According to GHS (Globally Harmonized Classification System) the test item Me-3K4A2 was not classified (LD50 cut-off: >5000 mg/kg body weight).