Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 Mar 2014 to 19 Mar 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

1
Chemical structure
Reference substance name:
3-(p-cumenyl)propionaldehyde
EC Number:
231-885-3
EC Name:
3-(p-cumenyl)propionaldehyde
Cas Number:
7775-00-0
Molecular formula:
C12H16O
IUPAC Name:
3-[4-(propan-2-yl)phenyl]propanal
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories, Inc.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 167-179 grams
- Fasting period before study: Prior to each dosing, experimentally naive rats (not previously tested) were fasted overnight by removing the feed from their cages
- Housing: The animals were singly housed in suspended stainless steel perforated bottom cages, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals. Enrichment (e.g., toy) was placed in each cage.
- Diet: Harlan Teklad Global 16% Protein Rodent Diet® #2016. The diet was available ad libitum, except during fasting.
- Water: Filtered tap water was supplied ad libitum.
- Acclimation period: 13-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 42-58
- Air changes (per hr): 11
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSE VOLUMES APPLIED:
The substance was applied unchanged at dose volumes of 0.35 - 0.38 mL

DOSE CALCULATIONS
Individual doses were calculated based on the initial body weights, taking into account the density (determined by PSL) of the test substance.

CLASS METHOD (if applicable)
A limit test at 2000 mg/kg bw was applied on three animals. Based on the survival of all animals in the short-term period following the 2000 mg/kg bw dose level, three additional females received a dose of 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Frequency of observations and weighing: The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing.
- Individual body weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 (terminal) following dosing
- Necropsy of survivors performed: All rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Cage-side observations performed: Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.
Statistics:
Statistical analysis was limited to the calculation of the mean density value for dosing.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived exposure to the test substance during the study.
Clinical signs:
Following administration, five animals were hypoactive and exhibited irregular respiration. However, the animals recovered by Day 1 and along with the remaining animals, appeared active and healthy for the remainder of the 14-day observation period.
Body weight:
Minor body weight loss observed in one animal was considered not to be of toxicological importance. All other animals gained body weight over the 14-day observation period.
Gross pathology:
No gross abnormalities were noted for these animals when necropsied at the conclusion of the 14-day study.

Applicant's summary and conclusion

Interpretation of results:
other: Not acutely harmful
Remarks:
in accordance with CLP (1272/2008 and its updates)
Conclusions:
The acute oral toxicity test showed an LD50 > 2000 mg/kg bw
Executive summary:

An acute oral toxicity test (Acute Toxic Class Method) was conducted according to OECD TG 423 and GLP principles. A Limit Test was conducted using a starting dose level of 2000 mg/kg bw administered to three healthy female Sprague-Dawley rats by oral gavage. Due to the absence of mortality in these animals, three additional females were dosed at the same dose level, simultaneously. Since all of these animals survived, no additional testing was required. During the observation period animals were assessed for clinical signs and body weight changes. In addition, at the end of the observation period the animals were subjected to examination for gross pathological changes.

Results: Following administration, five animals were hypoactive and exhibited irregular respiration. However, the animals recovered by Day 1 and along with the remaining animal, appeared active and healthy for the remainder of the 14-day observation period. Minor body weight loss observed in one animal was considered not to be of toxicological importance. All other animals gained body weight over the 14-day observation period. No gross abnormalities were noted for these animals when necropsied at the conclusion of the study. Based on these results, the LD50 of the test substance is > 2000 mg/kg bw.