Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented study according to international accepted guidelines and GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Test item: Tryptamine
CAS No.: 61-54-1
Batch No.: S37020N
Physical state: solid, amorphous powder
Colour: yellowish-brown
Active ingredient content: 99 %
Storage: 8-15 °C, protected from light and moisture

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Species and strain: Crl:(WI)Br rats
Source: TOXI COOP ZRT.
Hygienic level at arrival: SPF
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8 weeks old in first, second and third step
Body weight range: at starting (first step): 165 - 169 g
Body weight range: at starting (second step): 162 - 168 g
Body weight range: at starting (third step): 155 - 168 g
Housing: Group caging (3 animals/cage)
Light: Artificial light, from 6 a.m. to 6 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: 10-15 air exchanges/hour by central air-condition system.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Helianthi annui oleum raffinatum
Details on oral exposure:
A single oral administration - followed by a fourteen-day observation period - was performed by gavage.
Starting dose was selected on the basis of the available information about the test item. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. Since two female animals died on the treatment day and one animal died on Day 3, the test was continued at 300 mg/kg bw dose level on further three female rats.
No animal died in the second step at 300 mg/kg bw dose level, three further female rats were treated with the same (300 mg/kg bw) dose.

All doses were formulated in the vehicle. Concentration of formulations was adjusted to maintain a treatment volume of 10 mL/kg bw. The test item was applied in a concentration of 200 and 30 mg/mL. Formulations were prepared just before the administration and stirred continuously during the treatment.

The day before treatment the animals were fasted. The food but not water was withheld overnight. The food was given back 3 hours after the treatment.
Doses:
2000, 300 mg/kg bw
No. of animals per sex per dose:
3 female/dose
Control animals:
no
Details on study design:
The observation period was 14 days. Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, 5 h and 6 h after the treatment and twice each day for 14 days thereafter.
The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.
At the end of the observation period the survivor rats were sacrificed and necropsy were performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Two rats dosed at 2000 mg/kg bw TRYPTAMINE (CAS 61-54-1) died on the treatment day 1 hour after the treatment and one animal died on Day 3. All deaths seemed to be consequences of systemic toxic effect of the test item.
No death occurred at 300 mg/kg single oral dose of the test item. All female rats in step 2 and step 3 survived until the end of the 14-day observation period.
Clinical signs:
In group 1 treated with 2000 mg/kg dose:
Decreased activity (score -1; -3; -4), tremor (score +1; +2; +3), tonic convulsion (score +1), clonic convulsion (score +1; +2) abnormal gait (score +1; +4), lateral position (score +3; +4), decreased righting reflex (score -2; -3; -4), decreased grip- and limb tone (score -2; -3; -4), decreased abdominal tone (score -2; -3; -4), decreased skin turgor (score -2; -3; -4), decreased ear reflex (score -2; -3; -4), decreased plantar reflex (score -3; -4), blood around the nose (score +1; +2; +3), cyanosis (score +1; +2; +3; +4), piloerection (score +2; +3) and dyspnoea (score +2; +3) occurred in all animals. Decreased body tone (score -2; -3; -4) was observed in two animals. Pain reaction (score +1), vocalisation (score +1) were recorded in one animal. Increased body tone (score +2) was detected in one animal. The symptoms were observed between treatment day and Day 2.
In group 2 treated with 300 mg/kg bw dose:
Increased activity (score +1), restlessness (score +1) and abnormal gait (score +1) occurred in all animals. Increased respiration rate (score +1) was detected in one animal. Blood around the nose (score +1) and piloerection (score +1) were recorded in two animals. Decreased activity (score -1) was observed in one animal. The symptoms were observed between treatment day and Day 2.
In group 3 treated with 300 mg/kg bw dose:
Abnormal gait (score +1) and piloerection (score +1) occurred in all animals. Increased activity (score +1) was observed in two animals. All animals were free of symptoms on the treatment day and between Day 2 and Day 14.
Body weight:
The body weight and body weight gain data of group 1 (2000 mg/kg bw) could not be evaluated, because of mortalities. In group 2 and 3 (300 mg/kg bw) the mean body weight of the animals corresponded to their species and age throughout the study.
Gross pathology:
All rats treated with 2000 mg/kg bw dose of the test item spontaneously died during the study. Internal necropsy finding as bloody content in the intestines was observed in two animals of group 1. This alteration could be related to the test item toxic effect. An internal necropsy finding as autolysis was observed in one animal. It is normal physiological process after death.
All animals treated with 300 mg/kg bw dose survived until the scheduled necropsy on Day 15. Internal necropsy finding as pale kidneys was observed in one animal of group 2 and in an other animal of group 3. This alteration could not be related to the test item toxic effect, but was regarded an individual variation. Most likely the observation is a congenital anomaly. Slight hydrometra was detected in one animal of group 2 and in an other animal of group 3, as well as moderate hydrometra was observed in one female of the group 2. The hydrometra is physiological finding and connected to the cycle of the animal.

Any other information on results incl. tables

Groups

Treatment

Lethality

Test item

Dose (mg/kgbw)

Females

1

tryptamine
Step1

2000

3/3

2

tryptamine
Step2

300

0/3

3

tryptamine
Step3

300

0/3

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The method used, was not intended for the precise calculation of a precise LD50 value.
The test item was ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423.
Hazard Category: Acute Tox. 4
Executive summary:
   Dose (mg/kg bw)  Mortality (dead/treated)  LD50 (mg/kg bw)  GHS category
 300  0/6  between 300 and 2000  4