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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2014
Reliability:
2 (reliable with restrictions)
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
specific investigations: other studies
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
2014
Reliability:
2 (reliable with restrictions)
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
GLP compliance:
no
Type of method:
in vivo
Endpoint addressed:
other: absorption of carbon-14 radiolabelled alpha-olefin
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Bicester, UK.
- Age at study initiation: 9 weeks
- Weight at study initiation: na
- Fasting period before study:
- Housing: sawdust in solid-bottom, polypropylene cages. Bedding was changed once weekly.
- Diet (e.g. ad libitum): RM1 powdered diet (Special Diet Services Ltd., Stepfield, Witham, Essex, UK) was used. Diet was provided ad libitum prior to and throughout the Study.
- Water (e.g. ad libitum): local supply and provided in bottles, ad libitum prior to and throughout the study
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23° C
- Humidity (%): 40-70%
- Air changes (per hr): 14-15 air changes per hour
- Photoperiod (hrs dark / hrs light): Twelve-hour periods of light were cycled with twelve-hour periods of darkness

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Dosing solutions and dosing
The test material was formulated in corn oil as follows:
190µL of unlabelled alpha-olefin + 10µL of 14C-alpha olefin were added to 19.8mL of corn oil to provide a dosing solution of approximately 10µCi/100mg.

A single oral gavage of 100mg alpha olefin/kg bodyweight with a dosing volume of 10mL/kg bodyweight was given to each rat on the day of dosing.
Frequency of treatment:
single dose exposure
Post exposure period:
Urine and faeces collection and terminal samples
Urine and faeces samples were collected on dry-ice at 24 hour intervals after dosing for up to 96 hours.
On day four after dosing the animals were transferred to the post mortem room for termination.
Blood, liver, adipose and kidney samples were collected at termination and stored at -20°C for further investigation.
Details on study design:
Animals Rats in group 1 only, 1-Octene were housed in glass metabolism cages 24 hours prior to dosing and control faeces and urine were collected. Groups 2, 3 were housed in glass metabolism cages on day of dosing.
Examinations:
Urine samples, faeces samples, terminal blood samples, tissue samples (liver, kidney and adipose)
Details on results:
The total amount of radioactivity administered to each animal was calculated using the volume of dosing solution administered by oral gavage.

Table 1. Total radioactivity dosed to each animal

Group

Rat Number

Dosing volume administered (mL)

Total radioactivity dosed (dpm)

 

1-Decene

5

2.3

4308652.1

6

2.3

4308652.1

7

2.4

4495984.8

8

2.3

4308652.1

dpm = disintegrations per minute

Conclusions:
The radioactivity of 1-decene was rapidly excreted into the urine and faeces and most of recovered radiolabeled material was recorded in the first 48 hours after dosing. Low amount of radioacivity recovery was detected in urine, faeces, whole body terminal blood, liver, kidney and adipose tissue was 17%.
Executive summary:

The results of the study conducted on 1 -decene showed that radioactivity was rapidly excreted into the urine and faeces and most of recovered radiolabeled material in the urine and faeces was recorded in the first 48 hours after dosing. Low amount of radioacivity recovery was detected in urine, faeces, whole body terminal blood, liver, kidney and adipose tissue for 17%.

The low recoveries of radioactivity might be explained with oxidative metabolism of the olefins to metabolites which may be metabolised to acetate and acetone, and then converted to CO2 which is exhaled. Another hypotheses is the direct exhalation of the parent olefins from the lungs to a rapid volatilisation of the chemicals from the aqueous environment of the alveoli at a rapid rate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014

Materials and methods

GLP compliance:
no
Type of method:
in vivo
Endpoint addressed:
other: absorption of carbon-14 radiolabelled alpha-olefin

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Radiolabelled Test material : Carbon-14 labelled alpha-olefin 1-Decene (CAS No. 872-05-9)
Unlabelled Test material: Decene (CAS No. 872-05-9)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Bicester, UK.
- Age at study initiation: 9 weeks
- Weight at study initiation: na
- Fasting period before study:
- Housing: sawdust in solid-bottom, polypropylene cages. Bedding was changed once weekly.
- Diet (e.g. ad libitum): RM1 powdered diet (Special Diet Services Ltd., Stepfield, Witham, Essex, UK) was used. Diet was provided ad libitum prior to and throughout the Study.
- Water (e.g. ad libitum): local supply and provided in bottles, ad libitum prior to and throughout the study
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23° C
- Humidity (%): 40-70%
- Air changes (per hr): 14-15 air changes per hour
- Photoperiod (hrs dark / hrs light): Twelve-hour periods of light were cycled with twelve-hour periods of darkness

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Dosing solutions and dosing
The test material was formulated in corn oil as follows:
190µL of unlabelled alpha-olefin + 10µL of 14C-alpha olefin were added to 19.8mL of corn oil to provide a dosing solution of approximately 10µCi/100mg.

A single oral gavage of 100mg alpha olefin/kg bodyweight with a dosing volume of 10mL/kg bodyweight was given to each rat on the day of dosing.
Frequency of treatment:
single dose exposure
Post exposure period:
Urine and faeces collection and terminal samples
Urine and faeces samples were collected on dry-ice at 24 hour intervals after dosing for up to 96 hours.
On day four after dosing the animals were transferred to the post mortem room for termination.
Blood, liver, adipose and kidney samples were collected at termination and stored at -20°C for further investigation.
Details on study design:
Animals Rats in group 1 only, 1-Octene were housed in glass metabolism cages 24 hours prior to dosing and control faeces and urine were collected. Groups 2, 3 were housed in glass metabolism cages on day of dosing.

Examinations

Examinations:
Urine samples, faeces samples, terminal blood samples, tissue samples (liver, kidney and adipose)

Results and discussion

Details on results:
The total amount of radioactivity administered to each animal was calculated using the volume of dosing solution administered by oral gavage.

Any other information on results incl. tables

Table 1. Total radioactivity dosed to each animal

Group

Rat Number

Dosing volume administered (mL)

Total radioactivity dosed (dpm)

 

1-Decene

5

2.3

4308652.1

6

2.3

4308652.1

7

2.4

4495984.8

8

2.3

4308652.1

dpm = disintegrations per minute

Applicant's summary and conclusion

Conclusions:
The radioactivity of 1-decene was rapidly excreted into the urine and faeces and most of recovered radiolabeled material was recorded in the first 48 hours after dosing. Low amount of radioacivity recovery was detected in urine, faeces, whole body terminal blood, liver, kidney and adipose tissue was 17%.
Executive summary:

The results of the study conducted on 1 -decene showed that radioactivity was rapidly excreted into the urine and faeces and most of recovered radiolabeled material in the urine and faeces was recorded in the first 48 hours after dosing. Low amount of radioacivity recovery was detected in urine, faeces, whole body terminal blood, liver, kidney and adipose tissue for 17%.

The low recoveries of radioactivity might be explained with oxidative metabolism of the olefins to metabolites which may be metabolised to acetate and acetone, and then converted to CO2 which is exhaled. Another hypotheses is the direct exhalation of the parent olefins from the lungs to a rapid volatilisation of the chemicals from the aqueous environment of the alveoli at a rapid rate.