p-tert-butylcinnamaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A valid study is available for the analogue substance 3-(4-tert-butylphenyl)propionaldehyde. The study was performed in line with good scientific principles in basic compliance with agreed protocols, with no or minor deviations from standard testing guidelines. The read-across is considered to be suitable based on the structural and “mechanistic action” similarities between the target substance (3-(4-tert-butylphenyl)acrylaldehyde) and source substance (3-(4-tert-butylphenyl)propionaldehyde) and their similar physico-chemical properties.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

The test substance was administered to male and female rats by gavage in single doses of 2.4, 2.9, 3.2 or 4.2 mL per kg bw. After treatment the rats received stock diet and tap water ad libitum. They were observed for signs of intoxication during a 14 day period, after which autopsies were carried out on survivors and the LD50 was calculated.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(4-tert-butylphenyl)propionaldehyde

EC Number:

242-016-2

EC Name:

3-(4-tert-butylphenyl)propionaldehyde

Cas Number:

18127-01-0

IUPAC Name:

3-(4-tert-butylphenyl)propanal

Test material form:

other: Liquid

Details on test material:

- Physical state: Colourless liquid
- Molecular formula (if other than submission substance): C13H18O
- Molecular weight (if other than submission substance): 190.2814
- Smiles notation (if other than submission substance): CC(C)(C)c1ccc(CCC=O)cc1
- InChl (if other than submission substance): InChI=1/C13H18O/c1-13(2,3)12-8-6-11(7-9-12)5-4-10-14/h6-10H,4-5H2,1-3H3
- Structural formula attached as image file (if other than submission substance): see Fig. 1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, Netherlands.
- Age at study initiation: Young adult, age not specified.
- Weight at study initiation: Males 200 to 260 g, females from 100 to 134 g.
- Fasting period before study: Overnight
- Diet (e.g. ad libitum): Stock diet available ad libitum
- Water (e.g. ad libitum): Ad libitum
- Housing: In groups of 5 in stainless-steel cages with grid-bottom and front.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 1 °C
- Air changes (per hr): Well ventilated, but air changes not specified.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2.4, 2.9, 3.5 or 4.2 mL/kg bw

No. of animals per sex per dose:

Five/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Other examinations performed: Observed for signs of intoxication.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2.66 mL/kg bw

Based on:

test mat.

95% CL:

2.43 - 2.91

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 770 mg/kg bw

Based on:

test mat.

95% CL:

ca. 2 531 - 3 020

Remarks on result:

other: assuming a relative density of 0.96

Mortality:

Deaths occurred between 7 h and 3 days after dosing. Then the survivors recovered gradually and looked quite healthy at the end of the observation period.

Clinical signs:

other: Within a few hours after treatment the rats showed sedation and signs of ataxia. Later, signs of emaciation, encrustations around eyes and nostrils and coma were frequently observed.

Gross pathology:

Macroscopic examination of the survivors did not reveal any treatment-related gross alterations.

Any other information on results incl. tables

Table 1: Doses applied and mortality figures

Dose (mL/kg)	Mortality
	Number		Percent
	Males	Females
2.4	2/5	1/5	30
2.9	3/5	4/5	70
3.5	4/5	5/5	90
4.2	5/5	5/5	100

ANALOGUE APPROACH JUSTIFICATION:

- See attached “Justification for read-across” document for full details.

- In summary, important considerations for the use of read-across for acute oral toxicity are: i) 3-(4-tert-butylphenyl)acrylaldehyde (the target chemical) has similar predicted physico-chemical properties to those predicted and experimentally determined for 3-(4-tert-butylphenyl)propionaldehyde (the source substance), ii) there are structural similarities between the two chemicals and iii) the OECD QSAR Toolbox indicates that the two substances are expected to have similar interactions with biological receptors.

The information reported in this summary is included to demonstrate comparability between the source (3-(4-tert-butylphenyl)propionaldehyde) and target (3-(4-tert-butylphenyl)acrylaldehyde) substance.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was assessed for acute oral toxicity in rats using a single dose administered by oral gavage. The LD50 was calculated to be 2.66 mL/kg bw with 95 % confidence limits of 2.43 and 2.9 mL/kg bw (approximately 2770 mg/kg bw assuming a relative density of 0.96).

Executive summary:

The test substance was administered to male and female rats by gavage in single doses of 2.4, 2.9, 3.2 or 4.2 mL per kg bw. After treatment the rats received stock diet and tap water ad libitum. They were observed for signs of intoxication during a 14 day period, after which autopsies were carried out on survivors and the LD50 was calculated. The LD50 was calculated to be 2.66 mL/kg bw with 95 % confidence limits of 2.43 and 2.9 mL/kg bw (approximately 2770 mg/kg bw assuming a relative density of 0.96).