Registration Dossier

Administrative data

Description of key information

Acute Oral Toxicity : target : (1RS,4Z,8E,12RS)-13-oxabicyclo[10.1.0]trideca-4,8-diene : LD50 > 5000 mg/kg bw, 2020

Read-Across: source data : 1,5,10-trimethylcyclododeca-1,5,9-triene, epoxidized : Oral: measured LD50 > 2000 mg/kg bw and applicant assessment indicates LD50 -cut off > 5000 mg/kg bw, female rat, OECD TG 423, 2006

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07-18-07-2006 to 08-08-2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
inspected: August 2005 ; signature: November 2005
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl: CD (SD) IGS BR
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: 210 - 236 g (2000 mg/kg dose level) ; 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: 2006-07-18 to 2006-08-08
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not applicable.
- Amount of vehicle (if gavage): Not applicable.
- Justification for choice of vehicle: Not applicable.
- Lot/batch no. (if required): Not applicable.
- Purity: Not applicable.

MAXIMUM DOSE VOLUME APPLIED: 2.08 mL/kg

DOSAGE PREPARATION (if unusual): Not applicable.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data suggesting the test item was toxic, 2000 mg/kg was chosen as the starting dose.
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to and then 0.5, 1, 2, 4 hours after dosing; once daily. Individual bodyweights prior to and at 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg bw : No mortality (mortality : n = 0/6)
Clinical signs:
2000 mg/kg bw : hunched posture (6/6), lethargy (4/6), ataxia (4/6), increased salivation, (2/6), decreased respiratory rate (2/6) and noisy respiration (1/6). Females appeared normal two, three or four days after dosing.
Body weight:
2000 mg/kg bw : All females showed expected bodyweight gains over the study period (start 193 to 236 g / end 240 to 269 g)
Gross pathology:
2000 mg/kg bw : No abnormalities were noted at necropsy.
Other findings:
- Organ weights: Not applicable.
- Histopathology: Not applicable.
- Potential target organs: Not applicable.
- Other observations: Not applicable.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test item oral median LD50 was estimated to be greater than 2500 mg/kg bw in female Sprague-Dawley CD strain rats.
Executive summary:

The study was performed according to OECD 423 and EU Method B1 tris Acute Toxicity and according to GLP to assess the acute oral toxicity of the test item following a single oral administration in the Sprague-Dawley CD strain rat by the acute class method. A group of three fasted females was treated with the test item at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level. The test item was administered orally undiluted. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no mortalities. Clinical signs of toxicity included: hunched posture (6/6 females), lethargy (4/6), ataxia (4/6), increased salivation, (2/6), decreased respiratory rate (2/6) and noisy respiration (1/6). Females appeared normal two, three or four days after dosing. All females showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test item in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bw. Applicant assessment indicates: under the conditions of this study the acute toxicity estimate could be considered to be > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH.

Additional information

ORAL :

Key Study : OECD TG 423, 2006 : Read-Across SOURCE ( 1,5,10-trimethylcyclododeca-1,5,9-triene, epoxidized ) : The study was performed according to OECD 423 and EU Method B1 tris Acute Toxicity and according to GLP to assess the acute oral toxicity of the test item following a single oral administration in the Sprague-Dawley CD strain rat by the acute class method. A group of three fasted females was treated with the test item at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level. The test item was administered orally undiluted. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no mortalities. Clinical signs of toxicity included: hunched posture (6/6 females), lethargy (4/6), ataxia (4/6), increased salivation, (2/6), decreased respiratory rate (2/6) and noisy respiration (1/6). Females appeared normal two, three or four days after dosing. All females showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test item in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bw. Applicant assessment indicates: under the conditions of this study the acute toxicity estimate could be considered to be > 5000 mg/kg bw.

 

DERMAL:

No data.

INHALATION:

No data.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity: oral

 

The substance meets classification criteria under Regulation (EC) No 1272/2008 for Specific Target Organ Toxicity: Single Exposure – Category 3 : narcotic effects: H336

 

Ataxia, and lethargy was observed at Acute Oral : GHS Category 4 dose levels. All effects were transient in nature.