trans-hex-2-enal

Endpoint summary

Description of key information

The available data for this endpoint include two oral LD50 studies and a maximum tolerated dose study in rats. The lowest reported value of 780 mg/kg bw (Gaunt et al., 1971) has been used for classification.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1971

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Qualifier:

no guideline required

Principles of method if other than guideline:

Oral LD50 test (no further details available).

GLP compliance:

not specified

Test type:

other: Test type not reported

Limit test:

no

Specific details on test material used for the study:

No details reported.

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No details reported.

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No details reported.

Doses:

No details reported.

No. of animals per sex per dose:

No details reported.

Control animals:

not specified

Details on study design:

No details reported.

Statistics:

No details reported.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

780 mg/kg bw

Based on:

not specified

Mortality:

No details reported.

Clinical signs:

other: No details reported.

Gross pathology:

No details reported.

Other findings:

No details reported.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Oral LD50 values for the test substance were reported to be 780 -1130 mg/kg bw in rats.

Executive summary:

An oral LD50 range of 780-1130 mg/kg bw in rats has been reported. Therefore, the test item is classified as a Category 4 Acute toxicity (H302) according to CLP criteria (EC Regulation 1272/2008).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

SIngle dose toxicity study.

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
Hexenal (CAS 6728-26-3) was ontained from Sigma (St. Louis, Missouri).
- Expiration date of the lot/batch:
No details reported
- Purity test date:
The reported purity of the test item was 98% (test date not reported).


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:No details reported
- Stability under test conditions: The stability of dosing solutions for 1 week was confirmed by NMR spectroscopy. No further details reported.
- Solubility and stability of the test substance in the solvent/vehicle: Dosing solutions were prepared just before the first dose administration.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
No details reported.

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories (Raleigh, North Carolina)
- Age at study initiation: 6 weeks of age
- Weight at study initiation: No details reported
- Fasting period before study:The rats were not fasted before dosing
- Housing:5 rats/ cage
- Diet:Rat chow (Purina), ad libitium
- Water: ad libitium
- Acclimation period: 1.5 to 2 weeks

DETAILS OF FOOD AND WATER QUALITY: No details reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No details reported
- Humidity (%): No details reported
- Air changes (per hr): No details reported
- Photoperiod (hrs dark / hrs light): 12-hour day/night cycle

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

- VEHICLE
- Justification for use and choice of vehicle: No details reported.
- Amount of vehicle (if gavage): Dosing volume 2 ml/kg
- Purity: No details reported

Doses:

0, 50, 200 or 500 mg/kg bw

No. of animals per sex per dose:

15 males per dose.

Control animals:

yes

Details on study design:

Groups of 15 rats were dosed with 0, 50, 200, or 500 mg/kg bw by oral gavage. Five animals from each dose group were killed 1, 2, or 4 days after dosing. Body weights
were recorded at dosing and just before necropsy. Rats were anesthetized using Nembutal (100 mg/kg i.p.) and exsanguinated via the aorta.

Statistics:

No details reported.

Preliminary study:

No preliminary study was conducted.

Key result

Sex:

male

Dose descriptor:

other: Maximum Tolerated Dose

Effect level:

> 200 - < 500 mg/kg bw

Based on:

test mat.

Mortality:

One rat administered 500 mg/kg bw was killed on Day 3 of the study based on excessive weight loss.

Clinical signs:

other: No details reported.

Gross pathology:

At necropsy, lesions were observed in the stomach only, the severity and incidence increased in a dose dependent manner.
No significant lesions were observed in any other tissues. After a single dose of 50 mg/kg, there was slight edema in the stomach of 2 animals. At 200 or 500 mg/kg, there was necrosis of the forestomach mucosa with a prominent pseudomembrane
of fibrin, degenerative cells, and debris.

Other findings:

Histopathological findings were reported as follows:

50 mg/kg bw: After 1 day, there was minimal multifocal epithelial hyperplasia with mild mucosal edema in the forestomach and cellular infiltrates in the lamina propria at the gastric limiting ridge in one animal. These changes were also observed in another rat but only at the gastric limiting ridge. Similar forestomach changes were observed in some or most rats at 2 or 4 days, respectively.

200 mg/kg bw: After 1 day, there was severe, acute, locally extensive coagulative necrosis with multifocal erosions and severe submucosal edema in the forestomach of all rats. In 3 rats, the lesions at the gastric limiting ridge were characterized by multifocal erosions, mucosal edema, and hemorrhage. In the other 2 rats, there was necrosis and diffuse ulceration of the gastric limiting ridge. After 4 days, severe mucosal regeneration and epithelial hyperplasia with dysplasia were present in all rats, along with submucosal edema, neovascularization, and fibroblast proliferation.

500 mg/kg bw: After 1 day, there was erosion, with or without ulceration, and necrosis of the forestomach with significant edema, congestion, and infiltrates of neutrophils and macrophages. Hyperplasia of some sections of intact epithelium adjacent to the gastric limiting ridge were also observed as well as coagulative necrosis of the gastric limiting ridge with edema, hemorrhage, and cellular infiltrates of mainly neutrophils. Necrosis of the gastric limiting ridge, edema, and cellular infiltrates also occurred as well as diffuse coagulative necrosis or ulceration and erosion of the forestomach mucosa. After 4 days, there was diffuse necrosis of the forestomach mucosa, which extended in some cases into the muscularis mucosa. Variable lesions were observed in the glandular stomach of most rats. The lesions were characterized by multifocal ectatic glands filled with necrotic debris that were lined by regenerating epithelium with or without hemorrhage, submucosal edema, and cellular infiltrates that sometimes formed perivascular cuffs.

Interpretation of results:

study cannot be used for classification

Conclusions:

An oral LD50 was not determined from the results of this study. The test item was noted to cause a dose-related body weight loss and reduced body weight gain, as well as necrosis, ulcerative lesions, inflammation and hyperplasia of the stomach, predominantly in the forestomach.
As the function of the forestomach in rats is primarily for storage of food, it was considered by the authors that this may have increased the duration of exposure to the test item. Based on the structural differences between human and rodent stomachs therefore, the relevance of the forestomach changes to humans was considered to by the authors to be unclear.

Executive summary:

A single dose of the test substance was administered, by gavage, to male F344 rats, that were euthanised 1, 2, or 4 days after administration. The test item was noted to cause a dose-related body weight loss and reduced body weight gain, as well as necrosis, ulcerative lesions, inflammation and hyperplasia of the stomach, predominantly in the forestomach. An oral LD50 was not determined from the results of this study. 

As the function of the forestomach in rats is primarily for storage of food, it was considered by the authors that this may have increased the duration of exposure to the test item. Based on the structural differences between human and rodent stomachs therefore, the relevance of the forestomach changes to humans was considered to by the authors to be unclear.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1973

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Acute Oral LD50 in the rat
- Short description of test conditions: 10 animals/dose
- Parameters analysed / observed: Clinical signs

GLP compliance:

not specified

Test type:

other: No details reported.

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Smaple marking of test item '72-159'
- Expiration date of the lot/batch: No details reported.
- Purity test date: No details reported.


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
No details reported.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
No details reported.

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No details reported.

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No details reported.

Doses:

0.42, 0.66,1.04, 2.04, 5.0 g/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No details reported.
- Necropsy of survivors performed: No details reported.
- Other examinations performed:mortality and clinical signs.

Statistics:

No details reported.

Preliminary study:

No preliminary study was performed.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

850 mg/kg bw

Based on:

not specified

Mortality:

0.42 g/kg bw (420 mg/kg bw): 0/10 deaths
0.66 g/kg bw (660 mg/kg bw): 3/10 deaths (1 death on Day 1, 2 deaths on Day 2)
1.04 g/kg bw (1040 mg/kg bw): 8/10 deaths (6 deaths on Day 1, 1 death on Day 3, 1 death on Day 4)
2.04 g/kg bw (2040 mg/kg bw): 10/10 deaths on Day 1
5.0 g/kg bw (5000 mg/kg bw): 10/10 deaths on Day 1

Clinical signs:

other: 0.42 g/kg bw (420 mg/kg bw): no clinical signs reported 0.66 g/kg bw (660 mg/kg bw): no clinical signs reported 1.04 g/kg bw (1040 mg/kg bw): piloerection 2.04 g/kg bw (2040 mg/kg bw): laboured breathing, lethargy 5.0 g/kg bw (5000 mg/kg bw): laboured b

Gross pathology:

No details reported

Other findings:

No details reported.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 in rats was reported to be 850 mg/kg (650 -1050 mg/kg bw).

Executive summary:

The oral LD50 in rats was reported to be 850 mg/kg (650 -1050 mg/kg bw). Therefore, the test item is classified as a Category 4 Acute toxicity (H302) according to CLP criteria (EC Regulation 1272/2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

780 mg/kg bw

Quality of whole database:

This endpoint is fulfulled by a weight of evidence approach. Two LD50 studies (reliability score: 4) and a maximum tolerated dose study and 28-day toxicity study (reliability score: 2) are available.

Justification for classification or non-classification

The lowest oral LD50 in rats is reported to be within the range of 780-1130 mg/kg bw. This is supported by data from another oral LD50 study in rats (850 mg/kg bw) and a maximum tolerated dose study, whereby doses up to 500 mg/kg bw were tolerated. Therefore, the test item is classified as a Category 4 Acute toxicity (H302) according to CLP criteria (EC Regulation 1272/2008).