Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(3E)-4-[(1S,3aS,4R,7aS)-1,7a-dimethyloctahydro-4H-1,4-methanoinden-4-yl]pent-3-en-2-one
EC Number:
948-498-7
Cas Number:
143785-33-5
Molecular formula:
C17H26O
IUPAC Name:
(3E)-4-[(1S,3aS,4R,7aS)-1,7a-dimethyloctahydro-4H-1,4-methanoinden-4-yl]pent-3-en-2-one
Test material form:
liquid
Specific details on test material used for the study:
Physical appearance (with color): Colourless to yellow liquid
Storage Conditions: Ambient (21 to 29°C)
Date of Expiry: 20-12-2020

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 11 to 12 weeks
- Weight at study initiation: 167.58 g to 180.00 g
- Fasting period before study: overnight (16 to 18 hours)
- Housing: Three animals were housed in a standard polypropylene cage (Size: L 430 x B 285 x H 150 mm) with a stainless-steel mesh top grill having facilities for holding pelleted feed and drinking water in water bottles fitted with a stainless-steel sipper tube. Clean sterilized paddy husk was provided as bedding material.
- Diet: Altromin Maintenance Diet for rats and mice 1324 manufactured by Altromin Spezialfutter GmbH & Co. KG, ad libitum
- Water: ad libitum
- Acclimation period: Animals used for Step-I, Step-I confirmation, Step-II and Step-II confirmation were acclimatized for six, eight, ten and thirteen days, respectively

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6°C to 23.2
- Humidity (%): 41 to 66
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL for the 300 and 2000 mg/kg bw dose groups, respectively
- Amount of vehicle: 10 mL/kg body weight.
- Justification for choice of vehicle: The test item was found miscible in corn oil and corn oil is a universally accepted and routinely used vehicle in oral toxicity studies.

CLASS METHOD
- Rationale for the selection of the starting dose: A starting dose of 300 mg/kg body weight has been selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg body weight since there was no available data on the acute toxicity of the test item.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
Study Design:
- The test item was administered by oral gavage as a single dose of 300 mg/kg body weight to three female rats in "Step-I". No clinical signs of toxicity and mortality were observed at 300 mg/kg body weight in "Step-I". Hence, "Step-I confirmation" was conducted using three more female rats approximately after 48 hours of observation by administering a single dose of 300 mg/kg body weight of the test item. No clinical signs of toxicity and mortality were observed at 300 mg/kg body weight in "Step-I confirmation". "Step-II" was conducted using three more female rats approximately after 48 hours of observation by administering a single dose of 2000 mg/kg body weight. No clinical signs of toxicity and mortality were observed at 2000 mg/kg body weight in "Step-II". "Step-II" confirmation was conducted using additional three animals approximately after 48 hours of observation. No clinical signs of toxicity and mortality were observed at 2000 mg/kg body weight in "Step-II confirmation".

Observations:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All the animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 mins), 2 hrs (±10 mins), 3 hrs (±10 mins) and 4 hrs (±10 mins) post dosing on day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Observations included changes in skin, fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous systems and somatomotor
activity and behaviour pattern. Individual animal body weight was recorded on day 1 (before test item administration) and on day 8 and 15 during the observation period.
- Necropsy of survivors performed: yes, all the animals were sacrificed under carbon dioxide anaesthesia, subjected to necropsy and a complete gross pathological examination and the observations were recorded.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at 300 and 2000 mg/kg body weight.
Clinical signs:
No clinical signs of toxicity were observed at 300 and 2000 mg/kg body weight.
Body weight:
All the animals revealed a physiologically normal increase in body weight.
Gross pathology:
No gross pathological changes were observed in any of the animals at 300 and 2000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met