p-tert-butylcinnamaldehyde

Endpoint summary

Description of key information

The acute oral toxicity of the test material in rats was determined to be 2.6 mL/kg bw (95 % CI 2.43-2.9) (equivalent to approximately 2770 mg/kg bw when assuming a relative density of 0.96) in a study performed to a method similar to OECD 401.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

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

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.

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.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2.66 mL/kg bw

Based on:

test mat.

95% CL:

2.43 - 2.91

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.

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.

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One study available with a reliability score of 2 in accordance with the principles of assessing data quality as defined by Klimisch et al (1997). The study was assigned a reliability score of 2 as it was performed to a method which was in basic compliance with OECD 401 and was performed an analogue of the registered substance. The quality of the database is therefore high.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The test material 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).

The study was performed to method equivalent to a recognised standardised guideline, the study was assigned a reliability score of 2 in line with the principles defined in Klimisch et al (1997) as the study was performed on a structural analogue of the substance. Due to the structural and mechanistic similarities between the two substances, it was considered appropriate to use data from the source substance to represent the target substance.

Justification for selection of acute toxicity – oral endpoint
A single valid study was available on a suitable structural analogue. The study was performed to a method equivalent to a standardised guideline. Due to the structural and mechanistic similarities between the target and source substance, it was considered appropriate to use a read-across approach to address the acute oral toxicity endpoint.

Justification for classification or non-classification

On the basis that the results from the test material used in the acute oral toxicity study in rats, 3-(4-tert-butylphenyl)propionaldehyde, are being used to the support the registration of 3-(4-tert-butylphenyl)acrylaldehyde using a read-across approach, 3-(4-tert-butylphenyl)acrylaldehyde should therefore also be considered as not acutely toxic by the oral route. In accordance with Regulation 1272/2008 and Directive 67/548/EEC, the substance does not meet the classification criteria for acute toxicity by the oral route.