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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 May - 21 Jun 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 17 Dec 2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Citronellyl butyrate
EC Number:
205-463-4
EC Name:
Citronellyl butyrate
Cas Number:
141-16-2
Molecular formula:
C14H26O2
IUPAC Name:
citronellyl butyrate

Test animals

Species:
rat
Strain:
other: Crl:CD(SD), SPF
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: 172.3 - 193.1 g
- Fasting period before study: overnight, approx. 16 h prior and 4 h after dosing
- Housing: 1 animal per cage in stainless wire mesh cages (260W x 350D x 210H mm)
- Diet: Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C (Envigo RMS. Ltd., USA), ad libitum
- Water: public tap water filtered and irradiated by ultraviolet light, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 - 23.3
- Humidity (%): 43.1 - 59.7
- Air changes (per hr): 10 - 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: 400 mg/mL
- Lot/batch no.: MKBV2080V (SIGMA-ALDRICH, Co., USA)

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the low expected toxicity of the test substance 2000 mg/kg bw was selected as the starting dose.
Doses:
2000 mg/kg bw (Steps 1 and 2)
No. of animals per sex per dose:
3 females per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min and 1, 2, 4 and 6 h after dosing and thereafter once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes

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.
Remarks on result:
other: no mortality occurred in Step 1 and 2 at 2000 mg/kg bw in an OECD 423 study
Mortality:
No mortality was observed during the study period.
Clinical signs:
Abnormal gait was observed in all animals at 2000 mg/kg bw from 4 to 6 h after dosing. Mucous stool was observed in three animals and soiled perineal region and decrease of fecal volume were observed in each one animal on Day 1. These animals returned to a normal appearance on Day 2. These clinical signs were considered to be test substance-related.
Body weight:
A tendency to suppressed body weight gain was observed in one animal on Day 1. This animal returned to normal on Day 3. This change was considered to be test substance-related.
Gross pathology:
No grossly visible evidence of morphological abnormalities was observed in any animal.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats a LD50 cut-off of >= 5000 mg/kg bw was derived.
Executive summary:

There were no deaths of animals at 2,000 mg/kg. Abnormal gait was observed in animals at 2,000 mg/kg on the day of dosing. Mucous stool, soiled perineal region and/or decrease of fecal volume were observed in animals at 2,000 mg/kg on Day 1. These animals returned to a normal appearance on Day 2 after dosing. A tendency of suppressed body weight gain was observed in animals on Day 1 after dosing. Then, this animal returned to normal on Day 3. No test substance-related effects were observed in necropsy findings in any animal.

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