Oct-2-ene

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restrictions because it was GLP compliant and was generally conducted according to OECD 408 guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pent-1-ene

EC Number:

203-694-5

EC Name:

Pent-1-ene

Cas Number:

109-67-1

Molecular formula:

C5H10

IUPAC Name:

pent-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-Pentene
- Molecular formula (if other than submission substance): C5H10
- Substance type: C5 alpha olefin
- Physical state: Liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Centre of RRL
- Age at study initiation: 8 weeks
- Weight at study initiation: Males: 62.4 to 73.9 grams; Females: 60.1 to 78.4 grams
- Fasting period before study: No fasting
- Housing: Groups of four
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 22°C
- Humidity (%): 38 to 69%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 1993-9-14 To: 1993-12-14

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Mixed with vehicle; volumes ranged from 0.35 millilitre to 2.00 millilitres, adjusted for weight.

VEHICLE
- Concentration in vehicle: 280 mg/mL

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

Daily, 5 out of every 7 days

Doses / concentrations

Remarks:

Doses / Concentrations:
1000 mg/kg bw/day
Basis:
no data

No. of animals per sex per dose:

12

Control animals:

yes, concurrent vehicle

Details on study design:

Not detailed

Positive control:

None

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 4 times daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Pretest and 13 weeks

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Pretest and 13 weeks
- Dose groups that were examined: Control and 1000 mg/kg bw


HAEMATOLOGY: Yes
- Time schedule for collection of blood: 13 weeks
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: All animals
- Parameters checked in Table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 13 weeks
- Animals fasted: No
- How many animals: All animals
- Parameters checked in Table 2 were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Parameters checked in Table 3 were examined.

Other examinations:

Mean organ mass, as determined at post mortem examinations.

Statistics:

All test group results were analyzed to determine if they were significantly different from the control animals.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

There were no clinical signs related to treatment. There were no treatment-related changes in body weight, ophthalmology, haematology, clinical chemistry, organ weights, gross pathology, or histopathology.

CLINICAL SIGNS AND MORTALITY: During week 2, one male was sacrificed prematurely, due to accidental dosing of the test substance into the lungs. Seven males exhibited signs of skin injury during the treatment period, possibly caused during the dosing procedure. One female was sacrificed prematurely during week 6 due to a partially ruptured oesophagus, and one female died on day 33, showing severe centrilobular congestion and an enlarged heart with severe pericarditis and haemopericardium. These signs were determined to be unrelated to treatment.

BODY WEIGHT AND WEIGHT GAIN: No treatment-related effects were observed.

OPHTHALMOSCOPIC EXAMINATION: No treatment-related effects were observed.

HAEMATOLOGY: Platelet counts were somewhat higher in the treatment groups for both sexes, but not significantly when compared to historical data.

CLINICAL CHEMISTRY: No treatment-related effects were observed.

ORGAN WEIGHTS: No treatment-related effects were observed.

GROSS PATHOLOGY: Centrilobular hepatic congestion was observed in all the animals that died or were subjected to euthanasia, and was determined to be agonal and unrelated to the treatment.

HISTOPATHOLOGY: NON-NEOPLASTIC: Individual abnormal findings were unrelated to the test substance, or incidental. No treatment-related effects were observed.

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: overall effects and clinical signs; mortality; body weight; ophthalmoscopic examination; haematology; clinical chemistry; gross pathology; organ weights; histopathology

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

There were no clinical signs related to treatment. There were no treatment-related changes in body weight, ophthalmology, haematology, clinical chemistry, organ weights, gross pathology, or histopathology. The NOAEL for this study is considered to be 1000 mg/kg/day.

Executive summary:

Justification for Read Across

Several criteria justify the use of the read across approach to fill data gaps for Category C isomerised olefins using 1-pentene as an analog. Category C is comprised of isomerised olefins with a range of carbon numbers; 1-pentene is a C5 alpha olefin. Studies indicate that changing carbon number, location of the double bond, or addition of branching does not measurably alter the mammalian health endpoints. Additionally, an acute inhalation study for 1-pentene showed that the toxicity concerns through this route of exposure are relatively low; toxicity concerns for Category C isomerised olefins are also low for acute oral and dermal exposure.  1-Pentene’s chemical structure, according to the Cramer classification scheme, also indicates that it is relatively non-toxic.  This point is observed in a 90-day repeated dose oral exposure study, in which rats were dosed up to 1000 mg/kg/day (limit dose).  1-Pentene did not induce any chemical related affects in any of the treated animals.  As a result, all of the above information indicates a low hazard potential for human health for both compounds. There do not appear to be any toxicological differences between 1-pentene and Category C isomerised olefins.  Therefore, read across between 1 -pentene and Category C isomerised olefins can be justified.

 

In a 90-day oral toxicity study, 1-pentene in cottonseed oil was administered to twelve Sprague-Dawley rats/sex/dose at dose levels of 0 (vehicle control) or 1000 mg/kg/day (limit dose) via gavage, 5 days a week for 13 weeks. 

Two animals were euthanized and morbidity was subsequently associated with accidental dosing into the lungs or a ruptured oesophagus. One treated female died on day 33 with severe centrilobular congestion and an enlarged heart with severe percarditis and haemopericardium. There were no clinical signs related to treatment. There were no treatment-related changes in body weight, ophthalmology, haematology, clinical chemistry, organ weights, gross pathology, or histopathology. Based on the results presented above, it can be concluded that the test material administered orally for 90 days in a limit test did not induce any chemical related affects in any of the treated animals. Hence, the NOAEL for this study is considered to be 1000 mg/kg/day.

This study received a Klimisch score of 1 and is classified as reliable without restrictions because it was GLP compliant and was generally conducted according to OECD 408 guidelines. This study will influence the DNEL(s).