N-ethyl-p-methoxy-α-methylphenethylamine

Endpoint summary

Description of key information

Data available for the structurally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5).The studies are as mentioned below:

1.Acute oral toxicity study was performed in male Royal Hart Wistar rats using test chemical.50% mortality was observed at dose 130 mg/kg bw. Hence,LD50 value was considered to be 130 mg/kg bw,when rats were treated with test chemical orally.

2.Acute oral toxicity study was performed in six groups of five Male albino rats of the Charles River strain using test chemical at dose level of 100 ,215 ,464 ,1000 ,2150 and 4640 mg/kg bw.50% mortality was observed at dose 171 mg/kg bw (95% CI Limits:126-233 mg/kg bw).The animals were observed for mortality and pharmacotoxic signs at the following intervals: continuously for 5 hours, at 24 hours, and once daily thereafter for 13 days.Necropsies were performed on those animals which succumbed during the observation period. Clinical signs likepulse rate increase without fall in Bp, Slight dyspnea, salivation, ataxia, moderate hypoactivity ,slight sedation, tremors , clonic convulsions were observed at different doses.In necropsy findings,congestion of lungs , stomach and small intestine,edema of lungs,petechiae in the stomach,a clear fluid in the thoracic cavity,hemorrhages in the stomach were observed at different doses.Hence,LD50 value was considered to be 171 mg/kg bw,when rats were treated with test chemical orally.

Thus, based on the above summarised studies,N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5)and it’s structurally similar read across substance, it can be concluded that LD50 value is between 50-300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5)can be classified as “Category III” for acute oral toxicity.Hence,based on the data available for the structurally similar read across, test chemical N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5) is toxic in the dose range of 130-171 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:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

WoE report is based on two acute oral toxicity studies as-
1.and 2. Acute Oral toxicity test was carried out to study the effects of the test chemicals on rodents

GLP compliance:

not specified

Test type:

other: no data available

Limit test:

no

Specific details on test material used for the study:

- Name of test material: N-ethyl-p-methoxy-α-methylphenethylamine
- IUPAC name: N-ethyl-1-(4-methoxyphenyl)propan-2-amine
- Molecular formula: C12H19NO
- Molecular weight: 193.2881 g/mole
- Smiles : CCNC(C)Cc1ccc(OC)cc1
- Inchl: 1S/C12H19NO/c1-4-13-10(2)9-11-5-7-12(14-3)8-6-11/h5-8,10,13H,4,9H2,1-3H3
- Substance type: Organic
- Physical state: Liquid (Colorless to pale yellow)

Species:

rat

Strain:

other: 1.Royal Hart Wistar 2.Albino Charles River

Sex:

male

Details on test animals or test system and environmental conditions:

1.Details on test animal
TEST ANIMALS
- Weight at study initiation:136-160 g
- Housing:animals were placed in 7 x 7 x 14 in wire cages.

2.Details on test animal
TEST ANIMALS
- Weight at study initiation:158-328 g
- Fasting period before study: Food was withheld from all of the rats for 16 hours prior to the administration of the compound.
- Housing:The animals were group-housed by dosage level in metal cages suspended above the droppings with food and water available ad libitum.
- Diet (e.g. ad libitum):food was provided ad libitum
- Water (e.g. ad libitum): water was provided ad libitum

Route of administration:

other: 1.oral: unspecified 2.oral: gavage

Vehicle:

other: 1.not specified 2.methylcellulose

Details on oral exposure:

1.No data available
2.Details on exposure
VEHICLE
- Concentration in vehicle: 100 ,215 ,464 ,1000 ,2150 and 4640 mg/kg bw
- Amount of vehicle (if gavage):1.0 ml/100 g
- Justification for choice of vehicle: Test chemical was soluble in vehicle.

MAXIMUM DOSE VOLUME APPLIED:4640 mg/kg bw

DOSAGE PREPARATION (if unusual): The compound was orally administered in dilution in a 0.5 per cent aqueous dispersion of methylcellulose (Methocel).Each dosage level was individually prepared in a concentration which enabled the delivery of a constant volume of 1.0 ml/100 g.

Doses:

1. 130 mg/kg bw
2.100 ,215 ,464 ,1000 ,2150 and 4640 mg/kg bw

No. of animals per sex per dose:

1.Total:20 animals
2.Total:30 animals
100 mg/kg bw: 5 males
215 mg/kg bw: 5 males
464 mg/kg bw: 5 males
1000 mg/kg bw: 5 males
2150 mg/kg bw: 5 males
4640 mg/kg bw: 5 males

Control animals:

not specified

Details on study design:

1.No data available
2.Details on study design
- Duration of observation period following administration: 13 days
- Frequency of observations: The animals were observed for mortality and pharmacotoxic signs at the following intervals: continuously for 5 hours, at 24 hours, and once daily thereafter for 13 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

1.The LD50 values were obtained 72 hr post -administration of test chemical using 20 rats and estimated by Probit analysis.
2.No data available

Preliminary study:

No data available

Sex:

male

Dose descriptor:

LD50

Effect level:

130 - 171

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

1.50% mortality was observed at dose 130 mg/kg bw in treated rats
2.50% mortality was observed at dose 171 mg/kg bw

Clinical signs:

1.No data available
2.I. pharmacotoxic Signs and Necropsy Findings:
a. 100 mg/kg :
Within 30 minutes following compound administration slightly increased cardiac and respiratory rates were observed. Slight dyspnea, salivation, and ataxia were also observed. These signs continued through the first hour of observation. One-to-three hours following oral intubation of test chemical, the slight salivation and ataxia continued accompanied by slight piloerection and slight sedation.Other signs noted previously were absent at this time. Three-to-five hoursafter administration a decrease in cardiac rate was noted accompanied by slight dyspnea, moderate hypoactivity and slight sedation. At 24 hours all of the animals in this group had returned to normal and remained so for the balance of the 14-day observation period.

b. 215 mg/kg:
Those signs noted at 100 mg/kg were also observed at this Level, accompanied by tremors and clonic convulsions within 30 minutes following oral administration. These signs continued during the first hour. One rat succumbed during the first 30 minutes, 2 rats at one hour, and a 4th rat at 2 hours. At 3 hours, the one animal. Remaining exhibited dyspnea, salivation, and ataxia.

c. 464. 1000, 2150, and 4640 mg/kg bw:
All of the animals at those dosage levels succumbed within 60 minutes following oral intubation of test chemical and exhibited those signs noted at 100 and 215 mg/kg prior to death.

Body weight:

1.No data available
2.No data available

Gross pathology:

1.No data available
2.At dose 215 mg/g bw, Four-of-four animals which succumbed exhibited congestion and/or edema of the lungs. One-of-four showed mild congestion of the stomach, petechiae in the stomach and a clear fluid in the thoracic cavity.
At 464 mg/kg edema of the lungs, congestion of the lungs,congestion of the stomach and small intestine and hemorrhages in the stomach were observed at necropsy. These signs were also observed at the 1000, 2150 and 4640 mg/kg dosage levels. One animal in the 2150 mg/kg group also exhibited 2-3 mm. hemorrhages in the lung.

Other findings:

1.No data available
2.No data available

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The test chemical N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5) is toxic in the dose range of >300-526 mg/kg bw.

Executive summary:

Data available for the structurally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5).The studies are as mentioned below:

1.Acute oral toxicity study was performed in male Royal Hart Wistar rats using test chemical.50% mortality was observed at dose 130 mg/kg bw. Hence,LD50 value was considered to be 130 mg/kg bw,when rats were treated with test chemical orally.

2.Acute oral toxicity study was performed in six groups of five Male albino rats of the Charles River strain using test chemical at dose level of 100 ,215 ,464 ,1000 ,2150 and 4640 mg/kg bw.50% mortality was observed at dose 171 mg/kg bw (95% CI Limits:126-233 mg/kg bw).The animals were observed for mortality and pharmacotoxic signs at the following intervals: continuously for 5 hours, at 24 hours, and once daily thereafter for 13 days.Necropsies were performed on those animals which succumbed during the observation period. Clinical signs likepulse rate increase without fall in Bp, Slight dyspnea, salivation, ataxia, moderate hypoactivity ,slight sedation, tremors , clonic convulsions were observed at different doses.In necropsy findings,congestion of lungs , stomach and small intestine,edema of lungs,petechiae in the stomach,a clear fluid in the thoracic cavity,hemorrhages in the stomach were observed at different doses.Hence,LD50 value was considered to be 171 mg/kg bw,when rats were treated with test chemical orally.

Thus, based on the above summarised studies,N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5)and it’s structurally similar read across substance, it can be concluded that LD50 value is between 50-300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5)can be classified as “Category III” for acute oral toxicity.Hence,based on the data available for the structurally similar read across, test chemical N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5) is toxic in the dose range of 130-171mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

171 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from authoritative database

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

Data available for the structurally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5).The studies are as mentioned below:

1.Acute oral toxicity study was performed in male Royal Hart Wistar rats using test chemical.50% mortality was observed at dose 130 mg/kg bw. Hence,LD50 value was considered to be 130 mg/kg bw,when rats were treated with test chemical orally.

2.Acute oral toxicity study was performed in six groups of five Male albino rats of the Charles River strain using test chemical at dose level of 100 ,215 ,464 ,1000 ,2150 and 4640 mg/kg bw.50% mortality was observed at dose 171 mg/kg bw (95% CI Limits:126-233 mg/kg bw).The animals were observed for mortality and pharmacotoxic signs at the following intervals: continuously for 5 hours, at 24 hours, and once daily thereafter for 13 days.Necropsies were performed on those animals which succumbed during the observation period. Clinical signs likepulse rate increase without fall in Bp, Slight dyspnea, salivation, ataxia, moderate hypoactivity ,slight sedation, tremors , clonic convulsions were observed at different doses.In necropsy findings,congestion of lungs , stomach and small intestine,edema of lungs,petechiae in the stomach,a clear fluid in the thoracic cavity,hemorrhages in the stomach were observed at different doses.Hence,LD50 value was considered to be 171 mg/kg bw,when rats were treated with test chemical orally.

Thus, based on the above summarised studies,N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5)and it’s structurally similar read across substance, it can be concluded that LD50 value is between 50-300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5)can be classified as “Category III” for acute oral toxicity.Hence,based on the data available for the structurally similar read across, test chemical N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5) is toxic in the dose range of 130-171mg/kg bw.

Justification for classification or non-classification

Based on the above experimental studies on N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5)and it’s structurally similar read across substances, it can be concluded that LD50 value is between 50-300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,N-ethyl-p-methoxy-α-methylphenethylamine (14367-46-5)can be classified as “Category III” for acute oral toxicity.