6-cyclopentylidenehexanal

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 05 to 26 February 2013.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 without any deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

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:

Inspected on 2012-04-23&24 / Signed on 2012-07-18.

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

6-cyclopentylidenehexanal

Cas Number:

111998-18-6

Molecular formula:

C11 H18 O

IUPAC Name:

6-cyclopentylidenehexanal

Test material form:

liquid

Details on test material:

- Description: Colourless translucent liquid
- Storage conditions: Store in a cool, dry place with adequate ventilation. Keep away from incompatible materials, light, open flames, and high temperatures

Specific details on test material used for the study:

- Date received: 23 January 2013
- Storage condition of test material: 6°C±3°C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle, France)
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 185 - 219 g
- Housing: housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff (SAFE, A04), ad libitum.
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70%
- Air changes: between ten and fifteen changes per hour.
- Photoperiod: 12 h light/12 h darkness.

IN-LIFE DATES: From 05 to 26 February 2013.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: at 2000 mg/kg bw: none. At 300 mg/kg bw: water.

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.15 mL/kg bw

ADMINISTRATION OF TEST ITEM:
* In the first step: animals received an effective dose of 2000 mg/kg bw of the test item, administered by force-feeding under a volume of 2.15 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.
* In the second step: animals received an effective dose of 300 mg/kg bw of the test item (0.32 mL of the test item was added to 1.83 mL of distilled water), administered by force-feeding under a volume of 2.15 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

VEHICLE
- Amount of vehicle (if gavage): 1.83 mL (second step, at 300 mg/kg bw)
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 (2000 mg/kg bw) and 6 (300 mg/kg bw)

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, 1, 3 and 4 hours after test item administration and thereafter once daily for 14 days. Animals were weighed pretest (Day 0) and on Day 2, 7 and 14.
- Necropsy of survivors performed: Yes; Animals were killed on Day 14 and subjected to macroscopic examination.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

ca. 1 000 mg/kg bw

Based on:

test mat.

Mortality:

- At 2000 mg/kg b.w: it was noted the death of two rats (2/3), at 22 hours and 50 minutes post-dose.
- At 300 mg/kg b.w: no mortality occurred.

Clinical signs:

other: - At 2000 mg/kg b.w: the mortalities were preceded by decrease in spontaneous activity (2/2) and piloerection (1/2). Rigor mortis was noted before the necropsy (2/2). In the surviving animal treated at 2000 mg/kg b.w. (1/3), a decrease in spontaneous act

Gross pathology:

- At 2000 mg/kg b.w: the macroscopic examination revealed a thinning of the forestomach and of the corpus (2/2) associated with black and red spots on the forestomach and on the corpus (2/2).
- At 300 mg/kg b.w: the macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the test conditions, the oral LD50 for test item is higher than 300 mg/kg and lower than 2000 mg/kg bw and the LD50 cut-off may be considered as 1000 mg/kg bw in female rats. Therefore, it must be classified in Category 4 according to the CLP Regulation (EC) No. 1272/2008 and Globally Harmonized System (GHS).

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 3 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 2000 mg/kg bw and then 6 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 300 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

It was noted the death of two rats treated at 2000 mg/kg b.w. (2/3). The mortalities were preceded by decrease in spontaneous activity (2/2) and piloerection (1/2). Rigor mortis was noted before the necropsy (2/2). Decrease in body weight was noted in the two animals on the day of the death compared to day 0 (between -11% and -15%) The macroscopic examination revealed a thinning of the forestomach and of the corpus (2/2) associated with black and red spots on the forestomach and on the corpus (2/2). In the surviving animal treated at 2000 mg/kg b.w. (1/3), a decrease in spontaneous activity, bradypnea, total ptosis, and piloerection were noted during the first days of the test. The animal recovered a normal behaviour at 48 hours post-dose. An absence in body weight gain was noted on day 2 compared to day 0. Then, the body weight evolution remained normal. The macroscopic examination of this animal at the end of the study did not reveal treatment related changes.

No mortality occurred in animals treated at 300 mg/kg. A decrease in spontaneous activity (3/6), and piloerection (2/6) were noted during the first hours of the test. The animals recovered a normal behaviour at 4 hours post-dose. The body weight evolution remained normal during the study.The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Under the test conditions, the oral LD50 for test item is higher than 300 mg/kg and lower than 2000 mg/kg bw and the LD50 cut-off may be considered as 1000 mg/kg bw in female rats. Therefore, it must be classified in Category 4 (H302: Harmful if swallowed) according to the CLP Regulation (EC) No. 1272/2008 and Globally Harmonized System (GHS).

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