Alkenes C20+

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

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

Test material information

Constituent 1

Reference substance name:

Oct-1-ene

EC Number:

203-893-7

EC Name:

Oct-1-ene

Cas Number:

111-66-0

IUPAC Name:

oct-1-ene

Details on test material:

This substance is very similar in structure to the substance being registered.

- 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 or test system 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 / concentration:

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 reference chemical:

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:

Justification for Read Across:

Several criteria justify the use of the read across approach to fill data gaps formultiple carbon number isomerised olefinsubstances using linear alpha olefin substances. Studies indicate that changing the carbon number, the location of the double bond, or adding branching does not measurably alter effects on mammalian health endpoints. There is a consistent toxicity potency pattern for individual alpha olefins supported by a low toxicity concern for acute oral, dermal and inhalation exposure. These materials are slightly irritating to skin and slightly to non-irritating to eyes of rabbits. In repeat dose toxicity studies, hex-1-ene and tetradec-1 -ene have shown comparable levels of low toxicity, with female rats exhibiting alterations in body and organ weights and changes in certain haematological values at the higher doses tested; male rats exhibiting nephropathy presumed to be associated with the alpha2u-globulin protein. Screening studies indicate that they are not neurotoxic (for hex-1-ene and tetradec-1-ene), do not produce adverse effects on reproduction or foetal development (hex-1-ene and tetradec-1-ene), and are not genotoxic (hex-1-ene, oct-1-ene, dec-1-ene, dodec-1-ene, and tetradec-1-ene). Study results for the aforementioned endpoints indicate a low hazard potential for human health. Since the addition of branching does not measurably alter the results of studies on mammalian health endpoints, there should not be any singificant toxicological differences between substances inmultiple carbon number isomerised olefinsand linear alpha olefins.  Therefore, read across between these two categories can be justified.

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.