dec-1-en-4-yne

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29-08-2017 to 27-09-2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

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:

inspected: July 2017 ; signature: November 2017

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

dec-1-en-4-yne

EC Number:

813-331-8

Cas Number:

24948-66-1

Molecular formula:

C10H16

IUPAC Name:

dec-1-en-4-yne

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: Approximately 4 °C, in the dark under nitrogen
- Other: Slightly yellow

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan: WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat: Not applicable.
- Source: Recognised supplier (documented in the full study report)
- Females (if applicable) nulliparous and non-pregnant: Yes.
- Rationale for use of males: Not applicable.
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 161 - 211 g (300 mg/kg including sighting test; sentinel); 173 g (2000 mg/kg sighting test; sentinel) ; bodyweight variation did not exceed ±20% of the mean bodyweight at study initiation.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes and environmental enrichment.
- Historical data: The laboratory has a historic control dataset (not documented in the full study report).
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum (except for fasting period)
- Acclimation period: At least 5 days.
- Microbiological status when known: No issues reported within the study.
- Method of randomisation in assigning animals to test and control groups: Randomly allocated to cages after receipt.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: To: 2017-08-29 to 2017-09-27

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Identity: 2000 mg/kg bw: Not applicable ; 300 mg/kg bw: Arachis Oil BP.
- Concentration in vehicle: 2000 mg/kg bw: Not applicable. Unchanged (no vehicle). 300 mg/kg bw: 30 mg/mL
- Amount of vehicle (if gavage): 2000 mg/kg bw: Not applicable ; 300 mg/kg bw: Test Item dose volume was 10 mL/kg (of bodyweight) in Arachis Oil BP in both the range finding study: at 500 mg/kg and 2000 mg/kg bw and the main test: at 2000 mg/kg bw
- Justification for choice of vehicle: For the purpose of the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water. For the purpose of the 2000 mg/kg dose level, the test item was used as supplied.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw: 2.56 mL/kg ; 300 mg/kg bw: 10 mL/kg

DOSAGE PREPARATION (if unusual): Not applicable. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water. For the purpose of the 2000 mg/kg dose level, the test item was used as supplied.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 300 mg/kg was chosen as the starting dose. The toxicity of the test substance was assessed by stepwise treatment of females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

Doses:

300 mg/kg bw (initial sighting test and main study)
2000 mg/kg bw (initial sighting test)

No. of animals per sex per dose:

1 (sighting study) and 4 (main study) as applicable; total 5 per dose (in definitive test).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Clinical signs including body weight : Yes.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg bw (sentinel and definitive test): No mortality (0/5)
2000 mg/kg bw (sentinel): One mortality (1/1)

Clinical signs:

other: 300 mg/kg bw (sentinel and definitive test): No signs of systemic toxicity were noted. 2000 mg/kg bw (sentinel): hunched posture, pilo-erection, lethargy, body tremors or occasional body tremors, increased salivation, ataxia and splayed gait on day of dos

Gross pathology:

300 mg/kg bw (sentinel and definitive test): No abnormalities were noted at necropsy.
2000 mg/kg bw (sentinel): Abnormalities noted at necropsy were pale liver and pale kidneys..

Other findings:

- Organ weights: Not applicable.
- Histopathology: Not applicable.
- Potential target organs: Not applicable.
- Other observations: Not applicable.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the oral LD50 was estimated to be in the range of 300 - 2000 mg/kg bw in female Wistar rats.

Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test item was administered by oral gavage in an initial sighting study at 300 mg/kg bw in a solution in arachis oil BP and following an absence of toxicity then at 2000 mg/kg bw. The animal treated at a dose level of 2000 mg/kg was humanely terminated on 1 day after dosing. Subsequently, a further group of four fasted females was given a single oral dose of test item, at a dose level of 300 mg/kg body weight. There was no mortality at a dose level of 300 mg/kg. Hunched posture, pilo-erection, lethargy, body tremors or occasional body tremors, increased salivation, ataxia and splayed gait was noted during the day of dosing in the animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity and all animals showed expected gains in bodyweight over the study period at a dose level of 300 mg/kg. Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg, that was found dead, were pale liver and pale kidneys. No abnormalities were noted at necropsy, treated at a dose level of 300 mg/kg. Under the conditions of this study, the oral LD50 was estimated to be in the range of 300 - 2000 mg/kg bw in the female Wistar rat. The test item was classified as Acute Oral Toxicity: Category 4 according to Regulation (EC) 1272/2008.