6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-propionaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 October 2002 - 7 November 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

In the selection of doses, which are suggested to be one or more of the four fixed levels: 5, 50, 300 and 2000 mg/kg bw. Instead the doses of 200 and 2000 mg/kg bw were used.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-propionaldehyde

EC Number:

251-717-2

EC Name:

6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-propionaldehyde

Cas Number:

33885-51-7

Molecular formula:

C12H18O

IUPAC Name:

3-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)propanal

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: Wistar Crl: (WI) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sutzfeld, Germany
- Age at study initiation: young adults, 8-9 weeks
- Weight at study initiation: body weight variation did not exceed 20% of the sex mean
- Fasting period before study: ~20 h
- Housing: 3 animals per sex per cage in labelled Macrolon cages with purified sawdust as bedding material
- Diet: standard pelled laboratory animal diet, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ±3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.10 mL/kg (for 2000 mg/kg bw dose)

Doses:

200 and 2000 mg/kg bw

No. of animals per sex per dose:

3 (highest dose only females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed 30 minutes, 1, 2 and 4 hours after application and thereafter daily
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed by CO2 asphyxia, necropsied and subjected to examination for gross pathological changes.
- Body weights: Individual body weights were recorded immediately before treatment (day 1) and then on the 8th and 15th day of the observation period.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/3 animals died at 2000 mg/kg bw, 1/6 animals died at 200 mg/kg bw.

Mortality:

- 2000 mg/kg bw: 2/3 animals died.
- 200 mg/kg bw: 1/6 animals (0/3 females, 1/3 males) died.

Clinical signs:

- 2000 mg/kg bw: Lethargy, flat and hunched posture, tremors, rales, uncoordinated movements, slow breathing, piloerection was observed.
- 200 mg/kg bw: Females: lethargy, hunched posture, quick breathing, piloerection, salivation. Males: lethargy, flat and hunched posture, uncoordinated movements, piloerection, shallow respiration, ptosis, hypersensitivity to touch.

Body weight:

No treatment related changes were recorded in the body weights of the animals during the study period.

Gross pathology:

No abnormalities observed.

Applicant's summary and conclusion

Interpretation of results:

other: Harmful

Remarks:

in accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

The substance has an LD50 of between 200 and 2000 mg/kg bw in an OECD TG 423 test.

Executive summary:

The acute oral toxicity in female and male rats has been studied in accordance with OECD TG 423 and GLP principles. In this study, 9 Wistar rats (3 males and 6 females in total) were administered the substance at dose levels of 200 and 2000 mg/kg bw by oral gavage. Mortality was observed in 2 out of 3 female animals at the highest dose. One male out of six died when dosed with 200 mg/kw bw. Clinical signs observed were lethargy, flat and hunched posture, tremors, rales, uncoordinated movements, slow breathing and piloerection detected. These effects were more prominent in the highest dose group. No body weight or macroscopical abnormalities were detected. The acute oral LD50 for the substance in male and female rats was determined to be between 200 and 2000 mg/kg bw and to derive a point value the geometric mean was selected and resulted in an LD50 of 632 mg/kg bw.