1-methyl-3-phenylpropylamine

Endpoint summary

Description of key information

Acute oral toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the toxic nature of the test chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6).The studies are as mentioned below:

1. Acute Oral Toxicity Study of given test chemical was conducted as per OECD No. 423 on 6 female Wistar rats at the concentration of 2000 mg/kg bw. The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were re­corded on day 0 (prior to dosing) 7 and 14.Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild chromodacryorrhea from day 2 to 6 and with moderate to mild lethargy from day 3 to 9 post dosing followed by normal observation till day 14. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period post dosing. Hence the LD50 was considered to be >2000mg/kg bw, when female Wistar rats were treated with test chemical orally.

 2. The acute oral toxicity study was conducted by using test chemical in 40 male and female rats at the concentration of 2510, 3160, 3980 or 5000 mg/kg orally by gavage and observed for 14 days. In preliminary studies, dose levels of 316, 1260 and 5000 mg/kg resulted in mortality in 0/2, 0/2 and 2/2 rats from low to high dose. In main study, all animals were died at 5000 mg/kg bw, 9 animals died at 3980 mg/kg bw, 6 animals died at 3160 mg/kg bw and 4 animals died at 2510 mg/kg. Sedation and tremors were observed in treated rats. No gross pathological alterations were observed in treated male and female rats at necropsy. Therefore, LD50 was considered to be 2850 mg/kg bw, with 95% confidence limit of 2252-3608 mg/kg bw, when male and female rats were treated with test chemical via oral gavage route.

Thus, based on the above summarised studies, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across chemical, 1-methyl-3-phenylpropylamine is not likely to be toxic atleast in the dose range of >2000-2850 mg/Kg bw.

Acute Inhalation Toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the toxic nature of the test chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6). The studies are as mentioned below:

1. The acute inhalation toxicity study was conducted by using test chemical in rats at the concentration of 5000 mg/m3 inhaled as a Single dose. No mortality was observed at 5000 mg/m3. Therefore, LC50 value was considered to be >5000 mg/ m3 (>5 mg/L) when rats were exposed with test chemical by inhalation route.

2. The acute inhalation toxicity study was designed and conducted according to OECD Guideline 403 (Acute Inhalation Toxicity) by using test chemical in 10 (5 males and 5 females) Wistar rats at the concentration of 5 mg/L by inhalation: aerosol via nose only exposure. The aerosol was generated by the used of Nanotek aerosol generator (particle size less than 1 micron). All exposure was conducted in a dynamic nose-only cylindrical chamber built from stainless steel and glass. The chamber had a volume of 8 liters with inner and outer chamber to minimize the fluctuation in concentration and temperature. All the animals uniformly exposed to aerosol drug concentration. For the inhalation purpose the rats were placed in polycarbonate holder tubes positioned   radically around exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol. The chamber was maintained at a slightly negative pressure to prevent leakage of the test atmosphere from the system, as well as its dilution with outside air. The exhaust air was decontaminated by subsequent passage through 1% NaOH solution, silica gel and activated charcoal filters. In limit test, 10 healthy Wistar albino rats of both sex body weight 200±20 gm were selected for study after acclimatization. The test groups of animals were exposed to aerosol at the concentration of 5 mg/L for period of 4 hrs. After exposure all the animals were closely observed for any clinical signs of toxicity at various intervals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days. The necropsy was performed on all the animals at termination of experiment. All the albino rats exposed to aerosol at the concentration of 5 mg/L did not show any clinical signs of intoxication. Furthermore, no mortality was observed throughout the period of observation. After 72 hrs, the result obtained from limit test was confirmed in another 10 animal of both sex at similar concentration following same guideline. No mortality at the tested dose level of 5.0 mg/L throughout the period of observation after exposure. The test compound did not elicit any clinical signs of intoxication at the tested aerosol concentration of 5 mg/L observed for the period of 14 days. The body weight of all the animals recorded individually on day 7th and 14th (post treatment) showed normal gain as compared to day 0th. No gross pathological changes were observed. Therefore, LC50 was considered to be >5 mg/L (>5000 mg/m3), when male and female Wistar rats were exposed with test chemical via inhalation route by nose only exposure for 4 hours.

Thus, based on the above summarised studies for the Target chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) and it’s structurally similar read across substances, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) cannot be classified for acute inhalation toxicity. Hence, based on the data available for the structurally similar read across chemical, 1-methyl-3-phenylpropylamine is not likely to be toxic at least in the dose of >5 mg/L.

Acute Dermal toxicity: 

The study need not be conducted because the substance is a strong acid (pH<=2.0) or strong base (pH=> 11.5). The experimental pH of 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) was 11.6. Hence this endpoint was considered for waiver.

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 2 acute oral toxicity studies as- WoE-2 and WoE-3.
Acute Oral toxicity test was carried out to study the effects of the test chemicals on rodents.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

other: 1. Wistar 2. not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. TEST ANIMALS
- Source:Bharat Serum and Vaccines Limited, India.
- Age at study initiation:8- 11 weeks at the time of dosing.
- Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
- Weight at study initiation:Minimum: 181 g and Maximum: 213 g (Individual body weights were within ± 6% prior to treatment after overnight fasting)- Fasting period:Wistar rats were fasted for 16-18 hrs.
- Housing:The animals were housed individually in polycarbonate cages.
- Bedding:All cages were provided with corn cobs.
- Room Sanitation:The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle:All the cages and water bottles were changed at least twice every week.
- Diet (e.g. ad libitum):All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum.
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period:Animal nos. 1-3 were acclimatized for five days and 4-6 for seven days prior to administration of the test item.
ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 20.40°C and Maximum: 23.10°C
- Humidity (%):Minimum: 38.40 % and Maximum: 58.70 %
- Air changes (per hr):More than 12 changes per hour.
- Photoperiod (hrs dark / hrs light):12:12
2. not specified

Route of administration:

oral: gavage

Vehicle:

other: 1. corn oil 2. not specified

Details on oral exposure:

1. VEHICLE - Amount of vehicle (if gavage):10 ml
- Lot/batch no. (if required):MKBD4650
MAXIMUM DOSE VOLUME APPLIED:10 ml/kg body weight.
2. not specified

Doses:

1. 2000 mg/kg bw
2. 2510, 3160, 3980 and 5000 mg/kg

No. of animals per sex per dose:

1. 6 female rats
2. Total:40
2510 mg/kg bw: 5 male, 5 female
3160 mg/kg bw: 5 male, 5 female
3980 mg/kg bw: 5 male, 5 female
5000 mg/kg bw: 5 male, 5 female

Control animals:

other: 1. not specified 2. not specified

Details on study design:

1. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Daily
- Necropsy of survivors performed: yes
At the end of 14 day observation period, all the survived rats were euthanised by overdose of CO2 for external and internal observations.
- Other examinations performed: Clinical Observation - After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all the surviving animals were observed once a day during the 14 day observation period.
Body weight - All surviving rats were weighed on days 0 (prior to dosing), 7 and 14. Animals were weighed immediately after found dead.
other: Mortality - All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
2. - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and gross pathology were observed.

Statistics:

1. not specified
2. not specified

Preliminary study:

1. not specified
2. not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 850 mg/kg bw

Based on:

test mat.

95% CL:

2 252 - 3 608

Remarks on result:

other: 50% mortality was observed

Mortality:

1. No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period post dosing.
2. When treated with 5000 mg/kg bw, all animals were died, at 3980 mg/kg bw, 9 animals were died, at 3160 mg/kg bw, 6 animals were died and at 2510 mg/kg 4 animals were died.

Clinical signs:

other: 1. At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild ch

Gross pathology:

1. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice.
2. No gross pathological alterations were observed in treated male and female rats at necropsy.

Other findings:

1. No data available
2. No data available

Interpretation of results:

other: Not classified

Conclusions:

The test chemcial 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) is not likely to be toxic atleast in the dose range of >2000 - 2850 mg/Kg bw.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the toxic nature of the test chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6). The studies are as mentioned below:

1. Acute Oral Toxicity Study of given test chemical was conducted as per OECD No. 423 on 6 female Wistar rats at the concentration of 2000 mg/kg bw. The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were re­corded on day 0 (prior to dosing) 7 and 14.Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild chromodacryorrhea from day 2 to 6 and with moderate to mild lethargy from day 3 to 9 post dosing followed by normal observation till day 14. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period post dosing. Hence the LD50 was considered to be >2000mg/kg bw, when female Wistar rats were treated with test chemical orally.

2. The acute oral toxicity study was conducted by using test chemcial in 40 male and female rats at the concentration of 2510, 3160, 3980 or 5000 mg/kg orally by gavage and observed for 14 days. In preliminary studies, dose levels of 316, 1260 and 5000 mg/kg resulted in mortality in 0/2, 0/2 and 2/2 rats from low to high dose. In main study, all animals were died at 5000 mg/kg bw, 9 animals died at 3980 mg/kg bw, 6 animals died at 3160 mg/kg bw and 4 animals died at 2510 mg/kg. Sedation and tremors were observed in treated rats. No gross pathological alterations were observed in treated male and female rats at necropsy. Therefore, LD50 was considered to be 2850 mg/kg bw, with 95% confidence limit of 2252-3608 mg/kg bw, when male and female rats were treated with test chemical via oral gavage route.

Thus, based on the above summarised studies for the Target chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across chemical, 1-methyl-3-phenylpropylamine is not likely to be toxic atleast in the dose range of >2000-2850 mg/Kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 850 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from Peer-reviewed journal.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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 2 acute inhalation toxicity studies as- WoE-2 and WoE-3.
Acute Inhalation toxicity test was carried out to study the effects of the test chemicals on rodents.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

other: 1. not specified 2. Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

1. not specified
2. TEST ANIMALS
- Source: Institute for Industrial Research & Toxicology
- Age at study initiation: 7 to 9 weeks
- Weight at study initiation: Range of 200 ±20g
- Housing:Groups of 5 animals of similar sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
- Diet (e.g. ad libitum): conventional Laboratory diets, Pelleted feed supplied
- Water (e.g. ad libitum):Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad-libitum
- Acclimation period:20 healthy albino rats were selected and acclimatized for standard laboratory condition for period of 1 week in experimental room under veterinary examination.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 degree C
- Humidity (%): 30-60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.

Route of administration:

other: 1. inhalation 2. inhalation: aerosol

Type of inhalation exposure:

other: 1. not specified 2. nose only

Vehicle:

other: 1. not specified 2. Distilled water

Details on inhalation exposure:

1. not specified
2. GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:cylindrical chamber built from stainless steel and glass
- Exposure chamber volume: 8 liters
- Method of holding animals in test chamber:For the inhalation purpose the rats were placed in polycarbonate holder tubes positioned radically around exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol.
- Source and rate of air:The aerosol was generated by the used of Nanotek aerosol generator (particle size less than 1 micron)
- Method of conditioning air:The chamber was maintained at a slightly negative pressure to prevent leakage of the test atmosphere from the system, as well as its dilution with outside air.
- System of generating particulates/aerosols:Nanotek aerosol generator
- Treatment of exhaust air:The exhaust air was decontaminated by subsequent passage through 1% NaOH solution, silica gel and activated charcoal filters.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

not specified

Concentrations:

1. 5 mg/l in air (5000 mg/m3)
2. 5 mg/L (5000 mg/m3)

No. of animals per sex per dose:

1. not specified
2. 10 (5 males and 5 females)

Control animals:

not specified

Details on study design:

1. not specified
2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The body weight of all the animals was observed weekly on day 0 (Before treatment), 7th and 14th (post treatment)
- Necropsy of survivors performed: yes, Necropsy was carried out on all the animals that died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.
- Other examinations performed: All the animals were observed for mortality and signs of intoxication at various intervals for first 6 hours on the day of dosing and thereafter twice a day for 14 days.

Statistics:

1. not specified
2. not specified

Preliminary study:

1. not specified
2. not specified

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality was observed

Mortality:

1. No mortality was observed at dose 5 mg/l in air in treated rats
2. No mortality at the tested dose level of 5.0 mg/L throughout the period of observation after exposure.

Clinical signs:

other: 1. not specified 2. The test compound did not elicit any clinical signs of intoxication at the tested aerosol concentration of 5 mg/L observed for the period of 14 days

Body weight:

1. not specified
2. The body weight of all the animals recorded individually on day 7th and 14th (post treatment) showed normal gain as compared to day 0th.

Gross pathology:

1. not specified
2. No gross pathological changes were observed

Other findings:

1. not specified
2. not specified

Interpretation of results:

other: Not classified

Conclusions:

The test chemcial 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) is not likely to be toxic atleast in the dose of >5 mg/L (>5000 mg/m3) for acute inhalation toxicity.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the toxic nature of the test chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6). The studies are as mentioned below:

1. The acute inhalation toxicity study was conducted by using test chemical in rats at the concentration of 5000 mg/m3 inhaled as a Single dose. No mortality was observed at 5000 mg/m3. Therefore, LC50 value was considered to be >5000 mg/ m3 (>5 mg/L) when rats were exposed with test chemical by inhalation route.

2. The acute inhalation toxicity study was designed and conducted according to OECD Guideline 403 (Acute Inhalation Toxicity) by using test chemical in 10 (5 males and 5 females) Wistar rats at the concentration of 5 mg/L by inhalation: aerosol via nose only exposure. The aerosol was generated by the used of Nanotek aerosol generator (particle size less than 1 micron). All exposure was conducted in a dynamic nose-only cylindrical chamber built from stainless steel and glass. The chamber had a volume of 8 liters with inner and outer chamber to minimize the fluctuation in concentration and temperature. All the animals uniformly exposed to aerosol drug concentration. For the inhalation purpose the rats were placed in polycarbonate holder tubes positioned   radically around exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol. The chamber was maintained at a slightly negative pressure to prevent leakage of the test atmosphere from the system, as well as its dilution with outside air. The exhaust air was decontaminated by subsequent passage through 1% NaOH solution, silica gel and activated charcoal filters. In limit test, 10 healthy Wistar albino rats of both sex body weight 200±20 gm were selected for study after acclimatization. The test groups of animals were exposed to aerosol at the concentration of 5 mg/L for period of 4 hrs. After exposure all the animals were closely observed for any clinical signs of toxicity at various intervals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days. The necropsy was performed on all the animals at termination of experiment. All the albino rats exposed to aerosol at the concentration of 5 mg/L did not show any clinical signs of intoxication. Furthermore, no mortality was observed throughout the period of observation. After 72 hrs, the result obtained from limit test was confirmed in another 10 animal of both sex at similar concentration following same guideline. No mortality at the tested dose level of 5.0 mg/L throughout the period of observation after exposure. The test compound did not elicit any clinical signs of intoxication at the tested aerosol concentration of 5 mg/L observed for the period of 14 days. The body weight of all the animals recorded individually on day 7th and 14th (post treatment) showed normal gain as compared to day 0th. No gross pathological changes were observed. Therefore, LC50 was considered to be >5 mg/L (>5000 mg/m3), when male and female Wistar rats were exposed with test chemical via inhalation route by nose only exposure for 4 hours.

Thus, based on the above summarised studies for the Target chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) and it’s structurally similar read across substances, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) cannot be classified for acute inhalation toxicity. Hence, based on the data available for the structurally similar read across chemical, 1-methyl-3-phenylpropylamine is not likely to be toxic atleast in the dose of >5 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from study report.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Justification for type of information:

The study need not be conducted because the substance is a strong acid (pH<=2.0) or strong base (pH=> 11.5). The experimental pH of 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) was 11.6. Hence this endpoint was considered for waiver.

Endpoint conclusion

Quality of whole database:

Waiver

Additional information

Acute oral toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the toxic nature of the test chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6).The studies are as mentioned below:

1. Acute Oral Toxicity Study of given test chemical was conducted as per OECD No. 423 on 6 female Wistar rats at the concentration of 2000 mg/kg bw. The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were re­corded on day 0 (prior to dosing) 7 and 14.Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild chromodacryorrhea from day 2 to 6 and with moderate to mild lethargy from day 3 to 9 post dosing followed by normal observation till day 14. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period post dosing. Hence the LD50 was considered to be >2000mg/kg bw, when female Wistar rats were treated with test chemical orally.

 2. The acute oral toxicity study was conducted by using test chemical in 40 male and female rats at the concentration of 2510, 3160, 3980 or 5000 mg/kg orally by gavage and observed for 14 days. In preliminary studies, dose levels of 316, 1260 and 5000 mg/kg resulted in mortality in 0/2, 0/2 and 2/2 rats from low to high dose. In main study, all animals were died at 5000 mg/kg bw, 9 animals died at 3980 mg/kg bw, 6 animals died at 3160 mg/kg bw and 4 animals died at 2510 mg/kg. Sedation and tremors were observed in treated rats. No gross pathological alterations were observed in treated male and female rats at necropsy. Therefore, LD50 was considered to be 2850 mg/kg bw, with 95% confidence limit of 2252-3608 mg/kg bw, when male and female rats were treated with test chemical via oral gavage route.

Thus, based on the above summarised studies, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) cannot be classified for acute oral toxicity. Hence, based on the data available for the structurally similar read across chemical, 1-methyl-3-phenylpropylamine is not likely to be toxic atleast in the dose range of >2000-2850 mg/Kg bw.

Acute Inhalation Toxicity:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the toxic nature of the test chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6). The studies are as mentioned below:

1. The acute inhalation toxicity study was conducted by using test chemical in rats at the concentration of 5000 mg/m3 inhaled as a Single dose. No mortality was observed at 5000 mg/m3. Therefore, LC50 value was considered to be >5000 mg/ m3 (>5 mg/L) when rats were exposed with test chemical by inhalation route.

2. The acute inhalation toxicity study was designed and conducted according to OECD Guideline 403 (Acute Inhalation Toxicity) by using test chemical in 10 (5 males and 5 females) Wistar rats at the concentration of 5 mg/L by inhalation: aerosol via nose only exposure. The aerosol was generated by the used of Nanotek aerosol generator (particle size less than 1 micron). All exposure was conducted in a dynamic nose-only cylindrical chamber built from stainless steel and glass. The chamber had a volume of 8 liters with inner and outer chamber to minimize the fluctuation in concentration and temperature. All the animals uniformly exposed to aerosol drug concentration. For the inhalation purpose the rats were placed in polycarbonate holder tubes positioned   radically around exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol. The chamber was maintained at a slightly negative pressure to prevent leakage of the test atmosphere from the system, as well as its dilution with outside air. The exhaust air was decontaminated by subsequent passage through 1% NaOH solution, silica gel and activated charcoal filters. In limit test, 10 healthy Wistar albino rats of both sex body weight 200±20 gm were selected for study after acclimatization. The test groups of animals were exposed to aerosol at the concentration of 5 mg/L for period of 4 hrs. After exposure all the animals were closely observed for any clinical signs of toxicity at various intervals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days. The necropsy was performed on all the animals at termination of experiment. All the albino rats exposed to aerosol at the concentration of 5 mg/L did not show any clinical signs of intoxication. Furthermore, no mortality was observed throughout the period of observation. After 72 hrs, the result obtained from limit test was confirmed in another 10 animal of both sex at similar concentration following same guideline. No mortality at the tested dose level of 5.0 mg/L throughout the period of observation after exposure. The test compound did not elicit any clinical signs of intoxication at the tested aerosol concentration of 5 mg/L observed for the period of 14 days. The body weight of all the animals recorded individually on day 7th and 14th (post treatment) showed normal gain as compared to day 0th. No gross pathological changes were observed. Therefore, LC50 was considered to be >5 mg/L (>5000 mg/m3), when male and female Wistar rats were exposed with test chemical via inhalation route by nose only exposure for 4 hours.

Thus, based on the above summarised studies for the Target chemical 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) and it’s structurally similar read across substances, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) cannot be classified for acute inhalation toxicity. Hence, based on the data available for the structurally similar read across chemical, 1-methyl-3-phenylpropylamine is not likely to be toxic at least in the dose of >5 mg/L.

Acute Dermal toxicity: 

The study need not be conducted because the substance is a strong acid (pH<=2.0) or strong base (pH=> 11.5). The experimental pH of 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) was 11.6. Hence this endpoint was considered for waiver.

Justification for classification or non-classification

Based on the above experimental studies on 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) and it’s structurally similar and closely related read across substances, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity and LC50 value is >5 mg/L for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, 1-methyl-3-phenylpropylamine (CAS no.: 22374-89-6) cannot be classified for acute oral and inhalation toxicity. For acute dermal toxicity wavier was added so, not possible to classify.