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Basic toxicokinetics

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Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the information provided indicates that this study was conducted in a similar manner to OECD 417 guideline.
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:
basic toxicokinetics in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the information provided indicates that this study was conducted in a similar manner to OECD 417 guideline.
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
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
not specified
Principles of method if other than guideline:
Though a GLP guideline is not specified in the study, the study was performed in a manner similar to the OECD 417 guideline.
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 1-Octene
- Substance type: C8 alpha olefin
- Analytical purity: 99%
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mollegaard A/S, L1 Skensved, Denmark
- Weight at study initiation: 150 to 200 grams
- Housing: 4 animals/cage
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 4 to 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1
- Humidity (%): 70 +/- 20 RH
- Photoperiod (hrs dark / hrs light): 10 hrs dark/14 hrs light


Route of administration:
inhalation
Vehicle:
other: air
Details on exposure:
TYPE OF INHALATION EXPOSURE: Whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Conically shaped 0.7 cubic metre steel chambers with glass front door and walls
- Method of holding animals in test chamber: 4 animals/cage with 4 cages/chamber
- Source and rate of air: Source not provided; air rate at 5 m3/hr
- Concentration of test material in vehicle (if applicable): 100 parts per million in air


Duration and frequency of treatment / exposure:
All animals exposed for 12 hrs/day during daytime for 3 consecutive days.
Remarks:
Doses / Concentrations:
100 parts per million
No. of animals per sex per dose:
Authors state that 4 animals/cage with a maximum of 4 cages per exposure chamber were used. A total of six separate experiments were performed. Specific details regarding number of animals used per experiment are not provided.
Control animals:
not specified
Positive control:
Not applicable
Details on study design:
Details regarding dose selection or assignment of animals to the six experiments performed are not provided.
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): Blood, brain, liver, kidney, and fat
- Time and frequency of sampling: Immediately after 12 hrs exposure on days 1, 2, and 3 of the exposure period and 12 hrs after cessation of last exposure on day 3



Statistics:
Information regarding statistical analysis not provided.
Preliminary studies:
1-Octene showed efficient absorption in the blood with extensive accumulation in the organs as compared to the iso-alkanes. Accumulation also was shown to increase with increasing carbon number. At day 3, concentrations of 1-octene were 12.4±0.5, 69.7±4.0, 78.9±9.7, 139.3±23.4, 720±176 μmol/kg in the blood, brain, liver, kidney, and fat, respectively. Concentrations of the 1-alkenes remained high in the fat even after the 12 hour recovery period, with 226±85 μmol/kg of 1-octene. According to the study authors, the extensive accumulation of 1-alkenes in the blood and organs as compared to other hydrocarbons may have toxicological significance and, therefore, products containing 1-alkenes should be handled cautiously to minimize inhalation exposure.
Details on absorption:
1-Octene was efficiently absorbed into the blood.
Details on distribution in tissues:
1-Octene was distributed in the following manner in the male Sprague-Dawley rats: fat>kidney>liver>brain>blood following measurements taken aft12 hours on exposure days 1, 2, and 3. However distribution in tissues following measurements taken 12 hours after exposure had ceased, indicated that fat had the highest concentration of 1-octene followed by the liver.
Details on excretion:
Data not provided
Metabolites identified:
not specified
Conclusions:
Interpretation of results (migrated information): other: Several organs showed bioaccumulation during exposure and following exposure cessation. However, no data are provided for bioaccumulation potential several days after exposure ended.
According to the study authors, the extensive accumulation of 1-alkenes in the blood and organs as compared to other hydrocarbons may have toxicological significance and, therefore, products containing 1-alkenes should be handled cautiously to minimize inhalation exposure.
Executive summary:

Male Sprague-Dawley rats were acclimatized for 4 to 6 days prior to exposure. Animals were housed 4/ cage with the number of cages limited to 4 per exposure chamber. Food and water were givenad libitum, except during exposure period. Animals were exposed to individual hydrocarbons selected for the experiment in six different experiments. The approximate concentration of the hydrocarbons (1 -alkenes andiso-alkanes) tested was 100 parts per million. All exposures occurred during daytime for 12 hours for 3 consecutive days. Concentrations of the hydrocarbons was measured in blood, brain, liver, kidney and perirenal fat immediately after 12 hour exposure on each exposure day, and 12 hours after the last exposure had been completed. The animals were removed one at a time from the exposure chamber and killed by decapitation. A standard process, not described in the article, made it possible to obtain blood and organ samples within 3 minutes of removal of animals from the exposure chamber.

 

Experimental results indicated that 1-octene was efficiently absorbed in the blood with extensive accumulation in the organs compared to the iso-alkanes. Accumulation also was shown to increase with increasing carbon number. At day 3, concentrations of 1-octene were 12.4±0.5, 69.7±4.0, 78.9±9.7, 139.3±23.4, 720±176 μmol/kg in the blood, brain, liver, kidney, and fat, respectively. Concentrations of 1-decene were 16.4±1.1, 138.1±2.7, 192.8±13.5, 162±22.9, and 2986±305 μmol/kg at day 3 in the blood, brain, liver, kidney, and fat, respectively. Concentrations of the 1-alkenes remained high in the fat even after the 12 hour recovery period, with 226±85 μmol/kg of 1-octene and 1971±134 μmol/kg of 1-decene. According to the study authors, the extensive accumulation of 1-alkenes in the blood and organs when compared to other hydrocarbons may have toxicological significance and, therefore, products containing 1-alkenes should be handled cautiously to minimize inhalation exposure.

 

Based on study design and results, this study is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the information provided indicates that this study was conducted in a manner similar to OECD 417 guideline. 

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
not specified
Principles of method if other than guideline:
Though a GLP guideline is not specified in the study, the study was performed in a manner similar to the OECD 417 guideline.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1-Octene
- Substance type: C8 alpha olefin
- Analytical purity: 99%
Specific details on test material used for the study:
- Name of test material (as cited in study report): 1-Octene
- Substance type: C8 alpha olefin
- Analytical purity: 99%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mollegaard A/S, L1 Skensved, Denmark
- Weight at study initiation: 150 to 200 grams
- Housing: 4 animals/cage
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 4 to 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1
- Humidity (%): 70 +/- 20 RH
- Photoperiod (hrs dark / hrs light): 10 hrs dark/14 hrs light


Administration / exposure

Route of administration:
inhalation
Vehicle:
other: air
Details on exposure:
TYPE OF INHALATION EXPOSURE: Whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Conically shaped 0.7 cubic metre steel chambers with glass front door and walls
- Method of holding animals in test chamber: 4 animals/cage with 4 cages/chamber
- Source and rate of air: Source not provided; air rate at 5 m3/hr
- Concentration of test material in vehicle (if applicable): 100 parts per million in air


Duration and frequency of treatment / exposure:
All animals exposed for 12 hrs/day during daytime for 3 consecutive days.
Doses / concentrations
Remarks:
Doses / Concentrations:
100 parts per million
No. of animals per sex per dose:
Authors state that 4 animals/cage with a maximum of 4 cages per exposure chamber were used. A total of six separate experiments were performed. Specific details regarding number of animals used per experiment are not provided.
Control animals:
not specified
Positive control:
Not applicable
Details on study design:
Details regarding dose selection or assignment of animals to the six experiments performed are not provided.
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): Blood, brain, liver, kidney, and fat
- Time and frequency of sampling: Immediately after 12 hrs exposure on days 1, 2, and 3 of the exposure period and 12 hrs after cessation of last exposure on day 3



Statistics:
Information regarding statistical analysis not provided.

Results and discussion

Preliminary studies:
1-Octene showed efficient absorption in the blood with extensive accumulation in the organs as compared to the iso-alkanes. Accumulation also was shown to increase with increasing carbon number. At day 3, concentrations of 1-octene were 12.4±0.5, 69.7±4.0, 78.9±9.7, 139.3±23.4, 720±176 μmol/kg in the blood, brain, liver, kidney, and fat, respectively. Concentrations of the 1-alkenes remained high in the fat even after the 12 hour recovery period, with 226±85 μmol/kg of 1-octene. According to the study authors, the extensive accumulation of 1-alkenes in the blood and organs as compared to other hydrocarbons may have toxicological significance and, therefore, products containing 1-alkenes should be handled cautiously to minimize inhalation exposure.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
1-Octene was efficiently absorbed into the blood.
Details on distribution in tissues:
1-Octene was distributed in the following manner in the male Sprague-Dawley rats: fat>kidney>liver>brain>blood following measurements taken aft12 hours on exposure days 1, 2, and 3. However distribution in tissues following measurements taken 12 hours after exposure had ceased, indicated that fat had the highest concentration of 1-octene followed by the liver.
Details on excretion:
Data not provided

Metabolite characterisation studies

Metabolites identified:
not specified

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Several organs showed bioaccumulation during exposure and following exposure cessation. However, no data are provided for bioaccumulation potential several days after exposure ended.
According to the study authors, the extensive accumulation of 1-alkenes in the blood and organs as compared to other hydrocarbons may have toxicological significance and, therefore, products containing 1-alkenes should be handled cautiously to minimize inhalation exposure.
Executive summary:

Male Sprague-Dawley rats were acclimatized for 4 to 6 days prior to exposure. Animals were housed 4/ cage with the number of cages limited to 4 per exposure chamber. Food and water were givenad libitum, except during exposure period. Animals were exposed to individual hydrocarbons selected for the experiment in six different experiments. The approximate concentration of the hydrocarbons (1 -alkenes andiso-alkanes) tested was 100 parts per million. All exposures occurred during daytime for 12 hours for 3 consecutive days. Concentrations of the hydrocarbons was measured in blood, brain, liver, kidney and perirenal fat immediately after 12 hour exposure on each exposure day, and 12 hours after the last exposure had been completed. The animals were removed one at a time from the exposure chamber and killed by decapitation. A standard process, not described in the article, made it possible to obtain blood and organ samples within 3 minutes of removal of animals from the exposure chamber.

 

Experimental results indicated that 1-octene was efficiently absorbed in the blood with extensive accumulation in the organs compared to the iso-alkanes. Accumulation also was shown to increase with increasing carbon number. At day 3, concentrations of 1-octene were 12.4±0.5, 69.7±4.0, 78.9±9.7, 139.3±23.4, 720±176 μmol/kg in the blood, brain, liver, kidney, and fat, respectively. Concentrations of 1-decene were 16.4±1.1, 138.1±2.7, 192.8±13.5, 162±22.9, and 2986±305 μmol/kg at day 3 in the blood, brain, liver, kidney, and fat, respectively. Concentrations of the 1-alkenes remained high in the fat even after the 12 hour recovery period, with 226±85 μmol/kg of 1-octene and 1971±134 μmol/kg of 1-decene. According to the study authors, the extensive accumulation of 1-alkenes in the blood and organs when compared to other hydrocarbons may have toxicological significance and, therefore, products containing 1-alkenes should be handled cautiously to minimize inhalation exposure.

 

Based on study design and results, this study is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the information provided indicates that this study was conducted in a manner similar to OECD 417 guideline.