Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
The study was performed between 27 October 2009 and 02 December 2009.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection 15th September 2009 Date of signature 26th November 2009
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Sponsor's identification : Undecenyl methoxycrylene
Description : amber coloured viscous liquid
Batch number : ABP401608
Date received : 10 August 2009
Storage conditions : room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
Harlan Laboratories UK Limited, Bicester, Oxon, UK

- Age at study initiation:
At the start of the study the animals were eight to twelve weeks of age.

- Weight at study initiation:

- Fasting period before study:
An overnight fast immediately before dosing and for approximately three to four hours after dosing.

- Housing:
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.

- Diet (e.g. ad libitum):
Free access to food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK).

- Water (e.g. ad libitum):
Free access to mains drinking water.

- Acclimation period:
Acclimatisation period of at least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
19 to 25°C

- Humidity (%):
30 to 70%

- Air changes (per hr):
The rate of air exchange was at least fifteen changes per hour.

- Photoperiod (hrs dark / hrs light):
Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From: Day one To: Day fourteen

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
For the purpose of the study the test material was freshly prepared, as required, as a solution in arachis oil BP

- Justification for choice of vehicle:
Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.


MAXIMUM DOSE VOLUME APPLIED:
10 ml/kg.
The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.
Doses:
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
In the absence of toxicity at a dose level of 300 mg/kg, a dose level of 2000 mg/kg was chosen.
No. of animals per sex per dose:
One animal was treated at a dose level of 300 mg/kg.
A total of five animals were treated at a dose level of 2000 mg/kg in the study.
Control animals:
no
Details on study design:
- Duration of observation period following administration:
Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.

- Frequency of observations and weighing:
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed: yes
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Not applicable.

Results and discussion

Preliminary study:
Dose Level - 300 mg/kg
Individual clinical observations and mortality data are given in Table 1.

Mortality
There was no mortality.

Clinical Observations
No signs of systemic toxicity were noted during the observation period.

Bodyweight
Individual bodyweights and bodyweight changes are given in Table 2.
The animal showed expected gains in bodyweight over the observation period.

Necropsy
Necropsy findings are given in Table 3.
No abnormalities were noted at necropsy.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There was no mortality.
Mortality data are given in Table 4.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Individual clinical observations data are given in Table 4.
Body weight:
Individual bodyweights and bodyweight changes are given in Table 5.
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
Individual necropsy findings are given in Table 6.
No abnormalities were noted at necropsy.
Other findings:
Not applicable.

Any other information on results incl. tables

Table1              Individual Clinical Observations and Mortality Data -300mg/kg

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

300

1-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0


Table2              Individual Bodyweights and Bodyweight Changes -300mg/kg

Dose Level

mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g)
During Week

0

7

14

1

2

300

1-0 Female

210

230

238

20

8


Table3              Necropsy Findings -300 mg/kg

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

300

1-0 Female

Killed Day 14

No abnormalities detected


Table4              Individual Clinical Observations and Mortality Data -2000mg/kg

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0


Table5              Individual Bodyweights and Bodyweight Changes-2000mg/kg

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

2-0 Female

188

199

210

11

11

3-0 Female

177

183

193

6

10

3-1 Female

194

205

210

11

5

3-2 Female

185

191

195

6

4

3-3 Female

176

200

204

24

4


Table6              Individual Necropsy Findings-2000mg/kg

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

2-0 Female

Killed Day 14

No abnormalities detected

3-0 Female

Killed Day 14

No abnormalities detected

3-1 Female

Killed Day 14

No abnormalities detected

3-2 Female

Killed Day 14

No abnormalities detected

3-3 Female

Killed Day 14

No abnormalities detected


0= No signs of systemic toxicity

0= No signs of systemic toxicity

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).
Executive summary:

Introduction. 

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

§        OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (2001)

§        Method B1bisAcute Toxicity (Oral) of CommissionRegulation (EC) No. 440/2008

Method. 

Following a sighting test at dose levels of300 mg/kg and2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as asolutioninarachis oil BP, at a dose level of2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations. 

There were no signs of systemic toxicity.

Bodyweight. 

All animals showed expected gains in bodyweight.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than2000mg/kg bodyweight (Globally Harmonised Classification System-Unclassified).