3,4-dimethoxyphenethylamine

Endpoint summary

Description of key information

- oral LD50 in rat = 720.0 mg/kg

- inhalatory LC50 in rat > 5.5 mg/l; no mortality occured

- dermal LD50 in rabbit = 2800 mg/kg

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:

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

BASF-Test

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- doses: 1,470; 1,000; 681 and 464 mg/kg bw.
- concentrations [%]: 14.70; 10.00; 6.81 and 4.64
- appl. vol [mg/kg bw]: 10

Doses:

464; 681; 1,000 and 1,470 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: shortly before and 1 h; 1; 2, 7 and 14 adys after application; body weights: before; 2-4; 7 and 13 days after administration.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

720 mg/kg bw

Mortality:

Male animals:
At the highest dose level of 1470 mg/kg 1 animal was dead already 1 hour after administration and all had died after 24 hours.
At the levels of 1000 and 681 mg/kg 3 and 2 animals were dead after 24 hours, respectively.
At the lowest dose level no mortality was observed.

Female animals:
At the highest dose level of 1470 mg/kg 1 animal was dead already 1 hour after administration and all had died after 24 hours.
At the levels of 1000 and 681 mg/kg 3 animals were dead after 24 hours, respectively.
At the lowest dose level 2 animals were found dead after 24 hours.

Clinical signs:

other: Dyspnoea, apathy, abnormal body position, staggering, tremor, muscle-twitching, spasms, trismus, ruffled fur, erythema, cyanosis, salivation, bad general condition.

Gross pathology:

The animals which had died during the course of the study showed the following findings at necropsy: heart with acute dilatation at the right side and acute venous hyperemia; Liver with yellow broadened peripheral lobules; atonic intestines with strong mucosal erythema, diarrhoeic contents; atonic stomach with white gastric mucous membrane. The animals which survived until the end of the study showed no abnormalities at necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 was 720.0 mg/kg bw, with test substance homoveratrylamin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

720 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

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 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Method: BASF-test

GLP compliance:

no

Test type:

acute toxic class method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA Versuchstierzuchtanstalt, Sulzfeld
- Weight at study initiation: 185 +/- 15 g
- Fasting period before study:
- Diet (e.g. ad libitum): Herilan MRH, H. Eggersmann KG, Rinteln/Weseer, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

- inhalation period: 4 h
- observation period: 14 days
- Exposure system: head-to-nose inhalation system (animals were fixed in tubes, only their snouts were in the area of exposure).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5,53 mg/L; maximal attainable concentration.

No. of animals per sex per dose:

10

Control animals:

no

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.5 mg/L air

Exp. duration:

4 h

Mortality:

No mortalities.

Clinical signs:

other: Reddish secretion from eyes and nose, intermittent respiration, paddling movements, ruffled agglutinated fur.

Body weight:

Absolute body weights in males before inhalation/days after inhalation/14 days after inhalation: 187/213/259
Absolute body weights in females before inhalation/days after inhalation/14 days after inhalation: 181/197/217

Gross pathology:

No abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was > 5.5 mg/l with test substance homoveratrylamin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 500 mg/m³ air

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:

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)

Principles of method if other than guideline:

Method: other: BASF-test

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- source: SPF-Zucht, Hagemann, Externtal and WIGA, Sulzfeld, Germany
- mean body weights: 193 g (males) and 180 g (females).
- diet: Herilan MRH-Kraftfutter, H. Eggersmann, Rinteln/Weser, ad libitum
- water: ad libitum

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 cm²
- Type of wrap if used: inhert plastic film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1,000; 1,470; 2,000; 2,610 mg/kg bw.
- For solids, paste formed: no

Duration of exposure:

24 h

Doses:

1,000; 1,470; 2,000; 2,610 mg/kg bw.

No. of animals per sex per dose:

- 5 animals per sex at the 2,610 and 1,470 mg/kg bw dose level.
- 3 animals per sex at the 1,000 mg/kg bw dose level.
- 6 animals per sex at the 2,000 mg/kg bw dose level.

Control animals:

other: Untreated part of the skin.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 800 mg/kg bw

Mortality:

- dead male animals at the 2,610 mg/kg bw dose level after 1 h/ 24 h/48 h/7 days/14 days: 0/1/1/1/1
- dead female animals at the 2,610 mg/kg bw dose level after 1 h/ 24 h/48 h/7 days/14 days: 0/1/1/3/3
- dead male animals at the 2,000 mg/kg bw dose level after 1 h/ 24 h/48 h/7 days/14 days: 0/1/2/2/2
- dead female animals at the 2,000 mg/kg bw dose level after 1 h/ 24 h/48 h/7 days/14 days: 0/2/2/2/2
- dead male animals at the 1,470 mg/kg bw dose level after 1 h/ 24 h/48 h/7 days/14 days: 0/0/0/0/0
- dead female animals at the 1,470 mg/kg bw dose level after 1 h/ 24 h/48 h/7 days/14 days: 0/1/1/1/1
- dead male animals at the 1,000 mg/kg bw dose level after 1 h/ 24 h/48 h/7 days/14 days: 0/0/0/0/0
- dead female animals at the 1,000 mg/kg bw dose level after 1 h/ 24 h/48 h/7 days/14 days: 0/0/0/0/0

Clinical signs:

other: dyspnoe, apathy, excitation, aggressivness, staggering, tremor, twitch, spasmic gait, convulsions, deep yellow urine, piloerection, lacrimation, clotted eyes, vocalisation of pain, poor general state. Necroses at all dose levels.

Gross pathology:

- Animals that died in the course of the study: a) Heart: acute dilatation and acute venous hyperemia; b) Liver with slightly pale peripheral lobules; c) Kidney: grey-brown light-coloured kidneys (nephron necrosis).
- Animals that were sacrificed after the end of the study: no abnormalities detected.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was ca. 2800 mg/kg bw with the test substance homoveratrylamin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 800 mg/kg bw

Additional information

Acute oral toxicity:

In an acute oral toxicity study, groups of fasted young Wistar rats (5/sex) were given a single oral dose of the test substance at doses of 464, 681, 1000 and 1470 mg/kg. Animals were observed for 14 days. All animals died in the highest dosing group. At the lowest dosing group two female was found dead after 24 hours. At 1000 mg/kg three males and three females were found dead after 24 hours. At 681 mg/kg two male and three females were found dead after 24 hours. In all dosing groups dyspnoea, apathy, abnormal body position, staggering, tremor, muscle-twitching, spasms, trismus, ruffled fur, erythema, cyanosis, salivation, bad general condition was observed. The animals which had died during the course of the study showed the following findings at necropsy: heart with acute dilatation at the right side and acute venous hyperemia; Liver with yellow broadened peripheral lobules; atonic intestines with strong mucosal erythema, diarrhoeic contents; atonic stomach with white gastric mucous membrane. The animals which survived until the end of the study showed no abnormalities at necropsy. Based on the results of this study an LD50 of 720.0 mg/kg bw was determined (1978, reliability score: 2).

Acute inhalation toxicity:

In an acute inhalation toxicity study (comparable to OECD guideline 403) 20 Sprague-Dawley rats/dose (10/sex) were exposed head and nose only by the inhalation route to aerosols of the test substance in air for 4 hours at a saturated air concentration of 5.5 mg/L. Animals were then observed for 14 days. No mortality was observed within the 14 day observation period. Reddish secretion from eyes and nose, intermittent respiration, paddling movements and ruffled agglutinated fur was observed. No gross pathological findings were noted. The LD50 was > 5.5 mg/l with the test substance (1978, relability score: 2).

In an inhalation hazard test, 12 young adult rats per sex were exposed for 7 hours with the test substance. No mortalities observed, accelerated respiration was observed (1978, reliability score: 2).

Acute dermal toxicity:

In an acute dermal toxicity study equivalent to OECD guideline 402, groups of young adult Wistar rats (5/sex) were dermally exposed to the unchanged test substance at concentration of 1000, 1470, 2000 and 2610 mg/kg bw for 24 hours. Animals were then observed for 14 days.

At 2610 mg/kg and 2000 mg/kg 4 animals died. At 1470 mg/kg one animal died, in the low dose no animal died. Based on these findings an LD50 of ca. 2800 mg/kg bw was determined. In all dosing groups dyspnoe, apathy, excitation, aggressivness, staggering, tremor, twitch, spasmic gait, convulsions, deep yellow urine, piloerection, lacrimation, clotted eyes, vocalisation of pain, poor general state was observed. Necroses at all dose levels. Animals that died in the course of the study: a) Heart: acute dilatation and acute venous hyperemia; b) Liver with slightly pale peripheral lobules; c) Kidney: grey-brown light-coloured kidneys (nephron necrosis). Animals that were sacrificed after the end of the study: no abnormalities detected. Based on these findings an LD50 of ca. 2800 mg/kg bw was determined (1978, reliability score: 2).

Justification for classification or non-classification

Based on the results of the acute toxicity testing, the test item is classified as harmful if swallowed cat. 4 (H302) according to Regulation (EC) No 1272/2008 (CLP).