Octene, hydroformylation products, low-boiling

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 30 July 2008 and 27 August 2008.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection:21/08/2007 Date of signature: 15/10/2007

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octene, hydroformylation products, low-boiling

EC Number:

273-110-1

EC Name:

Octene, hydroformylation products, low-boiling

Cas Number:

68938-03-4

IUPAC Name:

Octene, hydroformylation products, low-boiling

Test material form:

liquid

Details on test material:

- Name of test material:
Oxooil LS9

- Physical state:
Clear colourless liquid

- Storage condition of test material:
Room temperature in the dark

-Date received:
14 July 2008

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:
At the start of the study the animals were eight to twelve weeks of age

- 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:
Overnight fast immediately before dosing

- Housing:
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

- 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 was allowed throughout the study

- Acclimation period:
At least five days

The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
The temperature was set to achieve limits of 19 to 25°C

- Humidity (%):
The relative humidity was set to achieve limits of 30 to 70%

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

- Photoperiod (hrs dark / hrs light):
The 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 0 To: Day 14

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
For the purpose of the 300 mg/kg dose level the test material was freshly prepared, as required, as a solution in arachis oil BP. For the purpose of the 2000 mg/kg dose level the test material was used as supplied

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

- Lot/batch no. (if required):
Not applicable

- Purity:
Determination by analysis of the concentration, homogeneity and stability of the test material preparations was not appropriate because it was not specified in the Study Plan and is not a requirement of the Test Guideline.

MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg bodyweight


DOSAGE PREPARATION (if unusual):
Not 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:

Sighting Test: 300 mg/kg and 2000 mg/kg
Main Test: 2000 mg/kg

No. of animals per sex per dose:

Sighting Test:
1 Female rat at 300 mg/kg
1 Female rat at 2000 mg/kg
Main Test:
4 Female rats at 2000 mg/kg

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 up to 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 or at death.

- Necropsy of survivors performed:
yes

- Other examinations performed:
behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects

Statistics:

Not recorded

Results and discussion

Preliminary study:

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

Remarks on result:

other: CL not recorded

Mortality:

One animal was found dead twelve days after dosing.

Clinical signs:

other: Signs of systemic toxicity noted in one animal during the observation period were hunched posture, pilo-erection, tiptoe gait, reduced respiratory rate and noisy respiration.

Gross pathology:

Individual necropsy findings are given in Table 6.
Abnormally red lungs, dark liver and dark kidneys were were noted at the necropsy of the animal that was found dead twelve days after dosing.

Other findings:

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

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	166	186	192	20	6

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	H Rd	H Rd	H Rd	H P	H P	0	0	0	0	0	0	Rn	Rn	H P Rn	H P Rn Wt	X

0= No signs of systemic toxicity                     Rn = Noisy respiration

H = Hunched posture                                         Wt = Tiptoe gait

Rd = Reduced respiratory rate                          X = Found dead

P = Pilo-erection

Table5               Individual Bodyweights and Bodyweight Changes-2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight (g) at Death	Bodyweight Gain (g) During Week
		0	7	14		1	2
2000	2-0 Female	158	177	196		19	19
	3-0 Female	171	178	196		7	18
	3-1 Female	176	190	217		14	27
	3-2 Female	170	174	194		4	20
	3-3 Female	182	186	-	144	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	Found dead Day 12	Abnormally red lungs Dark liver Dark kidneys

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

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.

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 B1bisAcute Toxicity (Oral) of Commission Directive 2004/73/EC

Method. 

Following a sighting test at dose levels of 300 mg/kg and2000 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 were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

One animal treated at a dose level of 2000 mg/kg was found dead twelve days after dosing. 

Clinical Observations. 

Signs of systemic toxicity noted in one animal treated at a dose level of 2000 mg/kg were hunched posture, pilo-erection, tiptoe gait, reduced respiratory rate and noisy respiration. 

Bodyweight. 

Surviving animals showed expected gains in bodyweight.

Necropsy. 

Abnormally red lungs, dark liver and dark kidneys were seen in the animal treated at a dose level of 2000mg/kg that was found dead twelve days after dosing.

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 . The clinical signs and necropsy observations of the animal that died on Day 12 of the observation period were consistent with partial aspiration of the dose material and not to toxicological effects.