4-(3-phenylpropyl)pyridine

Endpoint summary

Description of key information

Acute oral toxicity in rats: LD50 = 400 mg/kg bw. No acute dermal toxicity (LD50 > 2000 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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

standard acute toxicity procedure with 14 day observation

Principles of method if other than guideline:

A standard acute toxicity method was used in this test which predates establishment of OECD guidelines and GLP.

GLP compliance:

no

Remarks:

Predates GLP

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

other: Sherman-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Five groups of five male rats of the Sherman-Wistar strain weighing between 200 and 300 grams were used for the study.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The rats were deprived of food but not water 24 hours prior to dosing. Each animal was weighed and dosed by direct administration of the experimental material into the stomach by means of a syringe and dosing needle. The sample was doses as a 25% w/v suspension in corn oil.

Doses:

The doses given are the doses of suspension (25% in corn oil):
0.5 ml/kg, equivalent to 125 mg/kg bw,
1.0 ml/kg, equivalent to 250 mg/kg bw,
2.0 ml/kg, equivalent to 500 mg/kg bw,
4.0 ml/kg, equivalent to 1000 mg/kg bw,
8.0 ml/kg, equivalent to 2000 mg/kg bw.

No. of animals per sex per dose:

5 males were used per individual dose. 25 rats were used in total.

Control animals:

no

Details on study design:

Following administration of the test material, the animals were allowed food and water ad libitum for the 14 day observation period during which time the rats were observed for signs of toxicity and mortalities.

Statistics:

no data. Interpolation was undertaken, with 95% confidence limits established.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

400 mg/kg bw

Based on:

test mat.

95% CL:

> 250 - < 625

Mortality:

Mortalities were found in rats at doses of 1.0 mL/kg bw and above.
1 rat died at dose level of 1.0 mL/kg bw
3 rats died at dose level of 2.0 mL/kg bw
5 rats died at dose level of 4.0 mL/kg bw
5 rats died at dose level of 8.0 mL/kg bw

Clinical signs:

At 0.5 mL/kg bw (125 mg/kg bw), the rats appeared lethargic after 2 hours of dosing, but were normal after 24 hours. Weight gain in this group was below normal.
At 1.0 mL/kg bw (250 mg/kg bw), the rats were moderately depressed after one hour and did not appear normal after 72 hours with one death occuring. Weight gains were substantially below normal.
At 2.0 mL/kg bw (500 mg/kg bw), the rats were comatose after one hour with deaths occuring over the next 48 hours. Survivors did not appear normal for 5-7 days and lost weight at the conclusion of the study.
At 4.0-8.0 mL/kg bw, the rats become comatose after 30 minutes, and deaths occured in all animals within 4-8 hours.

Body weight:

Body weights of all rats were below normal levels, with the group 3 rats at 2.0 mL/kg bw (500 mg/kg bw) losing weight by the end of the study.

Gross pathology:

No abnormal gross pahtological signs were observed.

Many rats showed signs of lethargy, depression, and comatose states depending on their levels of dosing. Mortalities were seen above 0.5 mL/kg bw (125 mg/kg bw), and all rats died at 4.0 mL/kg bw (1000 mg/kg bw) and above. The LD50 of the test material was calculated to be 400 mg/kg bw.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

The LD50 was above 300 mg/kg bw and below 2000 mg/kg bw.

Conclusions:

In a study similar to OECD 401, the acute oral toxicity of the test material was investigated in male rats. The LD50 was between 250 and 500 mg/kg bw, and was calculated to be 400 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

400 mg/kg bw

Quality of whole database:

adequate

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Acute dermal toxicity method predates establishment of guideline methods

Principles of method if other than guideline:

A standard Acute Toxicity Method was used which predates established guidelines and GLP

GLP compliance:

no

Remarks:

predates GLP

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

All animals weighed between 2.5 and 3.0 kg.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

All animals had their backs clipped free of hair 24 hours prior to testing. All rabbits had their skin abraded prior to testing. Correct amount of experimental material was applied to the back of each animal. Treated areas were covered with large guaze patches and an impervious material was wrapped around the truck of each animal.

Duration of exposure:

The dressings were removed after 24 hours and any excess material was removed and the approximate amount remaining was noted. Each animal was observed for a period of 14 days for signs of toxicity.

Doses:

1.0 g/kg, equivalent to 1000 mg/kg bw,
2.0 g/kg, equivalent to 2000 mg/kg bw,
4.0 g/kg, equivalent to 4000 mg/kg bw.
8.0 gm/kg, equivalent to 8000 mg/kg bw.

No. of animals per sex per dose:

2 males and 2 females were each given one of the four available doses. 16 animals in total were used for the study.

Control animals:

no

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 000 mg/kg bw

Based on:

test mat.

95% CL:

> 2 700 - < 6 000

Mortality:

Mortality was seen in doses of 4.0 g/kg bw and 8.0 g/kw body weight.
At 4.0 g/kg bw, 2 of the 4 rabbits died within 48-72 hours of the study.
At 8.0 g/kg bw, 4 of the 4 rabbits died within 48 hours of the study.

Clinical signs:

At 4.0 g/kg bw, the animals were seen to be severely depressed after 6-8 hours exposure of the test material. Deaths occured 48-72 hours afterwards.
At 8.0 g/kg bw, the animals were comatose within 24 hours of exposure to the test material, and died prior to 48 hours.

Gross pathology:

Gross autopsies were performed on all animals which died during the 14 day observation period. Gross pathological examination revealed nothing remarkable.

Animals exposed to high dose levels of the test material expressed depression, and comatose states. Deaths were also indicated at higher dose levels from 4.0 -8.0 g/kg bw. The LD50 of the test material is estimated to be 4.0 g/kg bw, equivalent to 4000 mg/kg bw.

Interpretation of results:

GHS criteria not met

Remarks:

LD50 > 2000 mg/kg bw.

Conclusions:

The LD50 of the test material in albino rabbits is 4.0 g/kg bw, equivalent to 4000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Quality of whole database:

adequate

Additional information

Adverse effects were observed in rats at all doses administered orally in the acute oral toxicity study. At doses at and above the LD50 (400 mg/kg bw), the animals were comatose after 0.5 hour. At doses below the LD50, the animals displayed lethargy or depression, with diminished weight gain after 14 days. A second study indicated that the LD50 was greater than 500 mg/kg bw.

Justification for classification or non-classification

The substance is classified for acute oral toxicity, Category 4, according to Regulation EC No. 1272/2008, based on the oral LD50 in rats of 400 mg/kg bw (300 < LD50 < 2000 mg/kg bw). The substance does not meet the criteria for classification for acute dermal toxicity, with an LD50 of 4000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).