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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 July 2008 - 27 August 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols and GLP, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of Inspection - 21/08/07 Date of Signature - 15/10/07
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Dodecene, hydroformylation products, low-boiling
EC Number:
271-240-3
EC Name:
Dodecene, hydroformylation products, low-boiling
Cas Number:
68526-92-1
Molecular formula:
The substance consists of 46 isomers of unsaturated and branched dodecene structures (see Test Report No. A170002983).
IUPAC Name:
Dodecene, hydroformylation products, low-boiling
Details on test material:
Sponsor's identification : Oxooil LS 13 (CAS No. 68526-92-1)
Description : clear colourless liquid
Date received : 14 July 2008
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 UK Limited, Bicester, Oxon, UK.
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).
- Fasting period before study: One night before the start of the study
- Housing: housed in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access to food (Certified Rat and Mouse Diet) was allowed throughout the study
- Water (e.g. ad libitum):free access to mains drinking water (Certified Rat and Mouse Diet) was allowed throughout the study
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) followed by twelve hours of darkness.


IN-LIFE DATES: From: Day 0 To: Day 14

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/ml for 300 mg/kg dose level. Not stated for 2000 mg/kg.
- Amount of vehicle (if gavage): The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing.
- Justification for choice of vehicle: test material was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.
- Lot/batch no. (if required): Not stated
- Purity: Not stated


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg (300 dose level)
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe.

DOSAGE PREPARATION (if unusual): The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
Doses:
300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
1 female was dosed at 300 mg/kg; 5 females were dosed at 2000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
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.
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:
Statistics:
not stated in report

Results and discussion

Preliminary study:
Dose Level: 300mg/kg.
Mortality: There was no mortality.
Clinical Observations: No signs of systemic toxicity were noted during the observation period.
Bodyweight: The animal showed expected gains in bodyweight over the observation period.
Necropsy: No abnormalities were noted at necropsy.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: limit test: 1 female was dosed at 300 mg/kg; 5 females were dosed at 2000 mg/kg
Sex:
female
Dose descriptor:
other: LOAEL
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Signs of systemic toxicity noted in one animal treated at a dose level of 2000 mg/kg
Mortality:
For dose level 2000 mg/kg bw particular study there were no deaths.
Clinical signs:
Signs of systemic toxicity noted in one animal treated at a dose level of 2000 mg/kg were hunched posture, lethargy, ataxia, decreased respiratory rate and pilo-erection.
Body weight:
All animals showed expected gains in bodyweight.
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
- Other observations: None

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


0= No signs of systemic toxicity

Table 2               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

160

182

202

22

20

Table 3               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

Table 4               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

HLARd

H L A Rd

H LP

H P

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


0= No signs of systemic toxicity

H= hunched posture

L= lethargy

A= ataxia

Rd= decreased respiratory rate

P= pilo-erection

Table 5               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

157

167

190

10

23

3-0 Female

171

193

215

22

22

3-1 Female

156

168

180

12

12

3-2 Female

171

182

214

11

32

3-3 Female

178

186

206

8

20

Table 6               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

The acute oral median lethal dose (LD50) of the test material in the female Sprague Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.

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 Sprague Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight (EC Regulation 1272/2008 - not classified).
Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material in the Sprague‑Dawley CD 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 B1 bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC

Method. Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of undiluted test material at a dose level of 2000 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. Signs of systemic toxicity noted in one animal treated at a dose level of 2000 mg/kg were hunched posture, lethargy, ataxia, decreased respiratory rate and pilo-erection.

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 Sprague‑Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System-Category 5).