(1'R,2R)-2-Methyl-4-(2',2',3'-tri-nal and methylcyclopent-3'-en-1'-yl)-4-pent-enal

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29-11-1994 to 13-01-1995

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:

1995

Report date:

1995

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: October 1992 ; signature: December 1992

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

422-120-6

EC Name:

-

Cas Number:

166432-53-7

Molecular formula:

C14H22O

IUPAC Name:

2-methyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-enal

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: in the refrigerator in the dark
- Other: clear colourless liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl: CD (SD) BR strain (VAF plus)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised supplier
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 4 - 6 weeks.
- Weight at study initiation: 95-119 g (500 mg/kg and/or 2000 mg/kg bw range-finding test; sentinels); Main study: Male: 100-109 g and/or Female: 105 – 111 g (2000 mg/kg). Applicant assessment indicates: the weight variation did not exceed ±20% of the mean weight in the definitive test.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to five by sex ; in suspended grid-bottomed cages above carboard lined excreta trays.
- 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.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 24
- Humidity (%): 40 - 66%
- Air changes (per hr): Not reported, however reported as air conditioned
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: 29-11-1994 To: 21-12-1994

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: For the purpose of the range finding study: at 500 mg/kg and 2000 mg/kg bw dose levels the test item was freshly prepared, as required, as a solution in 0.5% CMC at 25 and 100 mg/mL to achieve the required does levels by bodyweight. For the main test: at 2000 mg/kg bw dose level the test item was freshly prepared, as required, as a solution in 0.5% CMC at 100 mg/mL to achieve the required does level by bodyweight.
- Amount of vehicle (if gavage): Test Item dose volume was 20 mL/kg (of bodyweight) in 0.5% CMC 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: The vehicle was selected based on trial formulations performed.
- Lot/batch no. (if required): See full study report.
- Purity: See full study report.

MAXIMUM DOSE VOLUME APPLIED: 500 mg/kg bw dose level: 20 mL/kg of test item in vehicle (0.5% CMC) ; 2000 mg/kg bw dose level: 20 mL/kg of test item in vehicle (0.5% CMC).

DOSAGE PREPARATION (if unusual): Not applicable. The test item was prepared in the vehicle.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 500 mg/kg was chosen as the starting dose based on guideline recommendations within the range-finding test in one female before dosing at 2000 mg/kg bw a further single female. The starting dose of the main test was based on the observations from the range-finding test (lack of mortality, no clinical signs of toxicity, expected gains in bodyweight up to day 7).

Doses:

500 mg/kg bw and 2000 mg/kg bw (range finding test)
2000 mg/kg bw (main study)

No. of animals per sex per dose:

500 mg/kg bw in 0.5% CMC vehicle (starting dose) : 1 female (range finding study)
2000 mg/kg bw in 0.5% CMC vehicle (follow up dose) : 1 female (range finding study).
2000 mg/kg bw: 5 males and 5 females (main study) as applicable; total 5 per sex per dose level

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. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

500 mg/kg bw (range finding test): No mortality
2000 mg/kg bw (range finding test and definitive test): No mortality

Clinical signs:

other: 500 mg/kg bw (range finding test): No signs of systemic toxicity were noted. 2000 mg/kg bw (range finding test and definitive test): No signs of systemic toxicity were noted.

Gross pathology:

500 mg/kg bw (range finding test): No abnormalties were noted at necropsy.
2000 mg/kg bw (range finding test and definitive test): No abnormalties were noted at necropsy in all females and 4/5 males. One male an enlarged spleen at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the oral LD50 was estimated to be greater than 2000 mg/kg bw in male/female rats. Under the conditions of this study and under the Globally Harmonized Classification System of Classification and Labelling of Chemicals (GHS), the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.

Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 under GLP to assess the acute oral toxicity of the test item following a single oral administration in the male/female Crl: CD (SD) BR (VAF plus) strain rat by the fixed dose method. The test item was administered by oral gavage in an initial range finding test at 500 mg/kg bw in a solution of 0.5% CMC (carboxymethyl cellulose) to one female and following an absence of toxicity then at 2000 mg/kg bw in 0.5% CMC (carboxymethyl cellulose) to one female. There was an absence of toxicity up to day 7 in both females. Subsequently, in a main study further groups of five fasted males and females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight in 0.5% CMC (carboxymethyl cellulose). No mortalities were observed. No significant clinical signs were noted and all maintained a healthy appearance throughout the observation period terminated on day 15. All males and females gained bodyweight. There were no abnormalties noted at necropsy in all females and 4/5 males. One male an enlarged spleen at necropsy. Under the conditions of this study, the oral LD50 was estimated to be greater than 2000 mg/kg bw in the male/female Crl: CD (SD) BR rat. Applicant assessment indicates that the estimated LD50 cut-off is considered to be > 5000 mg/kg bw on the basis of absence of significant clinical toxicological effects and/or bodyweight increases in all males/females.