1,5,10-trimethylcyclododeca-1,5,9-triene, epoxidised

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From July 18 to August 08, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on August 30, 2005/ signed on November 21, 2005)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,5,10-trimethylcyclododeca-1,5,9-triene, epoxidised

EC Number:

945-746-6

Molecular formula:

Not Applicable

IUPAC Name:

1,5,10-trimethylcyclododeca-1,5,9-triene, epoxidised

Test material form:

liquid

Details on test material:

- Physical state: Pale yellow liquid
- Storage condition of test material: refrigerator in the dark between 0 and 10°C under nitrogen

Test animals

Species:

rat

Strain:

other: Sprague Dawley CD rats

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 193-236 g
- Fasting period before study: Animals were fasted for overnight period before test item administration and for approximately 3-4 h after dosing.
- Housing: Animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, U.K.), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: At least 15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From July 18 to August 08, 2006

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. Specific gravity of test material is 0.965.

DOSE VOLUME APPLIED: 2.08 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: In the absence of data suggesting the test material was toxic, 2000 mg/kg bw was chosen as the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 h after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
- Necropsy of survivors performed: Yes; At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination.
- Other examinations performed: clinical signs, body weight

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed at 2000 mg/kg bw

Mortality:

No mortality was observed.

Clinical signs:

Signs of systemic toxicity noted during the study were hunched posture, lethargy, ataxia, increased salivation, decreased respiratory rate and noisy respiration. Animals appeared normal two, three or four days after dosing.

Body weight:

All animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

See the attached document for information on Tables of results 423 - Acute oral toxicity

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated oral LD50 is higher than 5000 mg/kg bw.

Executive summary:

In an acute oral toxicity study performed according to OECD Guideline No. 423 and in compliance with GLP, a group of three fasted female Sprague Dawley CD rats was treated with the test material at a dose level of 2000 mg/kg bw. This was followed by a further group of three fasted females at the same dose level. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality was observed. Signs of systemic toxicity noted during the study were hunched posture, lethargy, ataxia, increased salivation, decreased respiratory rate and noisy respiration. Animals appeared normal two, three or four days after dosing. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

 

Estimated Oral LD50 (female) > 5000 mg/kg bw.

Under the test conditions, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated oral LD50 is higher than 5000 mg/kg bw.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.