3-(p-methoxyphenyl)-2-methylpropionaldehyde

Endpoint summary

Description of key information

Acute oral toxicity: a study similar to OECDTG401: LD50 = 4000 mg/kg bw

Acute inhalation toxicity LC50 route to route extrapolation = 10400 mg/m3 being higher than 1910 mg/m3, which is the saturated vapour concentration of Canthoxal

Acute dermal toxicity: a study similar to OECDTG402: LD50 => 5000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 Nov 1979 to 27 Nov 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: At least 8 weeks old
- Weight at study initiation: 185 - 376 g
- Fasting period before study: 16 - 20 hours
- Housing: 5/cage in suspended wire mesh cages (20"x10"x7")
- Diet: Fresh purina rat chow was freely available
- Water: Fresh water was freely available
- Acclimation period: At least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 21 °C
- The room was reserved exclusively for rodents on acute tests and was kept clean in accordance with the standards of AAALAC.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2.47, 2.94, 3.51, 4.20 and 5.0 g/kg bw

No. of animals per sex per dose:

10 male rats per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Doses were selected at log intervals in an attempt to achieve wo partial kills, and if possible a zero kill and/ or a 100% kill.
- Frequency of observations: The rats were observed 3-4 hours after dosing and once daily for 14 days
- Necropsy of survivors performed: no, the animals were not examined for gross pathology.
- Other examinations performed: Mortality, toxicity and pharmacological effects

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

4 000 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 400 - <= 4 600

Mortality:

0/10, 0/10, 4/10, 4/10 and 9/10 animals died in the 14 day observation period after exposure to 2.47, 2.94, 3.51, 4.20, and 5.0 g/kg respectively. The animals died in the first 2 days after exposure.

Clinical signs:

other: 2.47 g/kg: On the day of dosing, lethargy, piloerection, ptosis and flaccid muscle tone were noted in less than half of -the animals. These signs were occasionally noted through Day 4. All animals were normal on Days 5 through 14. 2.94 g/kg: On the day o

Interpretation of results:

other: Not acute harmful

Remarks:

in accordance with EU CLP (1272/2008 and its updates)

Conclusions:

The acute oral toxicity test showed an LD50 of 4000 mg/kg bw. For GHS the substance needs to be classified as: May be harmful if swallowed (H303).

Executive summary:

A pre-guideline study, equivalent to OECD guideline 401, was performed to identify the acute oral toxicity of the test substance. In this study 10 male rats were administered with 1.73, 2.47, 3.51, 4.2 and 5.0 g/kg bw. 0/10, 0/10, 4/10, 4/10 and 9/10 animals died in the 14 day observation period after exposure to 1.73, 2.47, 3.51, 4.2 and 5.0 g/kg respectively. The following signs of toxicity were commonly noted in all dose groups: lethargy, ptosis, piloerection and flaccid muscle tone. In addition in the dose groups receiving 3.51 and 4.2 g/kg three animals were prostrate and one animal was comatose. Animals were not examined for gross pathology. Under the conditions of the test, the acute oral LD50 for the test substance in rat was determined to be 4000 mg/kg bw. Based on these results, the test substance is not considered to be acute harmful.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 Aug 1980 to 30 Sep 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nicolas Helf, Ace Animals
- Age at study initiation: 8 weeks
- Weight at study initiation: 2.1 - 3.0 kg
- Housing: 2/ cage in suspended wire mesh cages
- Diet: Fresh Purina rabbit chow was freely available
- Water: Water was freely available
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
The room, reserved exclusively for rabbits on acute tests, was temperature controlled and was kept clean in accordance with the standards of AAALAC.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Immediately prior to dosing, the fur was clipped from the abdomen at an area of 200 cm²
- Coverage: 10%
- Type of wrap if used: Gauze patches secured with adhesive tape. The trunks were wrapped with impervious material.
- Other: Abrasions were made in 1/2 of the rabbits. The abrasions, extending the length of the exposure site, scratched the stratum corneum but did not reach the derma or produce bleeding.

DOSE VOLUME:
- 10.3 to 14.7 cc

REMOVAL OF TEST SUBSTANCE
- Washing: The exposure site was wiped, but not washed
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

5.0 g/ kg

No. of animals per sex per dose:

10 animals (6 males, 4 females): First 2 animals were dosed at 5.0 g/ kg. If no deaths occurred, additional animals were dosed at 5.0 g/kg. If more than one half of the animals died at the 5.0 g/ kg level, the LD50 was determined.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Dermal reactions were scored at 1, 7 and 14 days by the Draize scoring system.
- The rabbits were observed daily for 14 days for signs of toxicity, pharmacological effects and mortality.
- Body weights were recorded pretest and in the survivors at 14 days.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

0/10 animals died on the first day in the 14 day observation period after exposure to 5.0 g/kg test substance.

Clinical signs:

other: - Temporary diarrhea or decreased feces observed in six animals. - In one animal alopecia and ptosis was observed.

Gross pathology:

At necropsy 6/10 rabbits had scaly treated skin. The internal organs on superficial examination appeared normal.

Other findings:

Erythema and edema, generally slight on days 1 and 7, cleared by day 14.

Interpretation of results:

other: Not acute harmful

Remarks:

in accordance with EU CLP (1272/2008 and its updates)

Conclusions:

The acute dermal toxicity test showed an LD50 > 5000 mg/kg bw.

Executive summary:

A pre-guideline study, equivalent to OECD guideline 402, was performed to identify the acute dermal toxicity of the test substance. In this study 10 rabbits (6 male, 4 female) were administered with 5000 mg/kg test substance on the intact or scratched skin. The animals were exposed for 24 hours under occlusive conditions. None of the animals died in the 14 day observation period after exposure to the test substance. Slight to moderate erythema and edema, were observed on days 1 and 7 in 6 animals, but was cleared by day 14. Systemic effects included diarrhea or decreased feces in six animals and in one animal alopecia and ptosis were observed. 4/10 animals exhibited a slight weight loss during the 14 day observation period. Under the conditions of the test, the acute dermal LD50 for the substance in rabbits was > 5000 mg/ kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute oral toxicity

A pre-guideline study, equivalent to OECD guideline 401, was performed to identify the acute oral toxicity of the test substance. In this study 10 male rats were administered with 1.73, 2.47, 3.51, 4.2 and 5.0 g/kg bw. 0/10, 0/10, 4/10, 4/10 and 9/10 animals died in the 14 day observation period after exposure to 1.73, 2.47, 3.51, 4.2 and 5.0 g/kg respectively. The following signs of toxicity were commonly noted in all dose groups: lethargy, ptosis, piloerection and flaccid muscle tone. In addition in the dose groups receiving 3.51 and 4.2 g/kg three animals were prostrate and one animal was comatose. Animals were not examined for gross pathology. Under the conditions of the test, the acute oral LD50 for the test substance in rat was determined to be 4000 mg/ kg bw.

Other information: In the RIFM database in a supporting study (1979) the material was tested at several doses. At 5000 mg/kg 9/10 animals died. At 4200 mg/kg 4/10 animals died. The LD50 was calculated to be 4000 mg/kg.

Acute inhalation toxicity

The acute inhalation toxicity for the substance can be derived using data on the acute oral toxicity using the following methodology: CLP guidance (2017; 3.1.5.1.8. Example 8, page 264): using the extrapolation formula 1 mg/kg bw = 0.0052 mg/L/4h. The LD50 of the substance for acute oral toxicity is 4000 mg/kg bw. This value can be converted to 20.8 mg/L or 20.8 g/m³. Taking into account the inhalation absorption as 100% and oral absorption 50%, the acute inhalation toxicity would become 10.4 g/m³= 10400 mg/m³. The maximum saturated vapour concentration for the substance is 1910.8 mg/m³ (0.3 Pa (vapour pressure) x 178 (MW)) / (8.3 (R, gas constant) x 297 (°K)). This means that the substance cannot reach a concentration higher than 1910.8 mg /m³ indicating that the LC50 cannot be reached because it exceeds the saturated vapour pressure.

Acute dermal toxicity

A pre-guideline study, equivalent to OECD guideline 402, was performed to identify the acute dermal toxicity of the test substance. In this study 10 rabbits (6 male, 4 female) were administered with 5000 mg/kg test substance on the intact or scratched skin. The animals were exposed for 24 hours under occlusive conditions. None of the animals died in the 14 day observation period after exposure to the test substance. Slight to moderate erythema and edema, were observed on days 1 and 7 in 6 animals, but was cleared by day 14. Systemic effects included diarrhea or decreased feces in six animals and in one animal alopecia and ptosis were observed. 4/10 animals exhibited a slight weight loss during the 14 day observation period. Under the conditions of the test, the acute dermal LD50 for the substance in rabbits was > 5000 mg/ kg bw.

Other information: In the RIFM database there is a supporting acute dermal study (1999) rabbits were dosed up to 2000 mg/kg bw. At that dose 0/10 died. The LD50 from this study is >2000 mg/kg bw.

Justification for classification or non-classification

Based on the available information classification and labelling for acute oral, dermal and inhalation toxicity is not warranted in accordance with EU CLP (EC No. 1272/2008 and its updates).