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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from publication.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats.
Author:
H. P. Til, H. E. Falke, M. K. Prinsen, and M. I. Willems
Year:
1997
Bibliographic source:
Food and Chemical Toxicology, Volume 35, Issues 3–4, March–April 1997, Pages 337-348
Reference Type:
review article or handbook
Title:
Aliphatic and aromatic amines and amides
Author:
World Health Organization
Year:
2006
Bibliographic source:
WHO Food Additives Series No. 56, pg. 327-395, 2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Acute oral toxicity study of 4-hydroxyphenethylammonium chloride (CAS no: 60-19-5) in rat.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-hydroxyphenethylammonium chloride
EC Number:
200-462-5
EC Name:
4-hydroxyphenethylammonium chloride
Cas Number:
60-19-5
Molecular formula:
C8H11NO.ClH
IUPAC Name:
4-hydroxyphenethylammonium chloride
Details on test material:
- IUPAC Name: 4-hydroxyphenethylammonium chloride
- Common Name: Tyramine
- InChI: 1S/C8H11NO.ClH/c9-6-5-7-1-3-8(10)4-2-7;/h1-4,10H,5-6,9H2;1H
- Smiles: c1cc(CCN)ccc1O.Cl
- Molecular formula:C8H12ClNO
- Molecular weight:173.642 g/mole
- Substance type:Organic
- Physical state:No data
- Purity: 99%
- Impurities:1%
Specific details on test material used for the study:
- IUPAC Name: 4-hydroxyphenethylammonium chloride
- Common Name: Tyramine
- InChI: 1S/C8H11NO.ClH/c9-6-5-7-1-3-8(10)4-2-7;/h1-4,10H,5-6,9H2;1H
- Smiles: c1cc(CCN)ccc1O.Cl
- Molecular formula:C8H12ClNO
- Molecular weight:173.642 g/mole
- Substance type:Organic
- Physical state:No data
- Purity: 99%
- Impurities:1%

Test animals

Species:
rat
Strain:
other: Cpb:WU; Wistar random, SPF-bred rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: The rats were obtained from TNO
Central Institute for the Breeding of Laboratory
Animals, Zeist, The Netherlands.
- Age at study initiation: 8-13 week old
- Weight at study initiation: Rats weighing 184-390g (males) and 130-232 g (females).
- Fasting period before study: Rats were fasted overnight, prior to dosing.
- Housing: Rats were housed conventionally under barrier conditions, in suspended stainless-steel cages fitted with wire mesh floor and front, two rats per cage.
- Diet (e.g. ad libitum): Rats were fed the Institute's basal diet, which is a cereal-based open formula diet.
- Water (e.g. ad libitum):
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%):55 ± 15%.
- Air changes (per hr): The number of air changes was about 10/hr.
- Photoperiod (hrs dark / hrs light): Artificial light
was provided continuously, for 12 hr/day from 07.30 hr until 19.30 hr.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqueous dilution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25%
Doses:
125 mg/kg, 250 mg/kg, 500 mg/kg , 1000 mg/kg and 2000 mg/kg bw
No. of animals per sex per dose:
Total = 20
Groups of 2 male and 2 female rats
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes, the animals that died and the survivors killed after 14 days.
- Other examinations performed: Animals were observed for mortality and clinical signs.
Statistics:
not specified

Results and discussion

Preliminary study:
not specified
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
No mortality was observed at 2000 mg/kg bw
Clinical signs:
other: Most of the animals showed sluggishness and Piloerection. Exophthalmus was seen in the 1000 and 2000 mg/kg groups.
Gross pathology:
not specified
Other findings:
not specified

Any other information on results incl. tables

Table: Mortality figures and 'approximate LD50' values of male and female rats administered single oral doses of five biogenic amines.

Dose levels

(mg/kg)

No. of rats that died in the various groups+

Tyramine

M

F

125

0

0

250

0

0

500

0

0

1000

0

0

2000

0

0

Approximate LD50 value (mg/kg)          >2000

 

+ No. of deaths in groups, which initially consisted of two male (m) and two female (f) rats per group.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
The acute oral toxicity dose (LD50) was considered to be >2000 mg/kg bw, when male and female Cpb:WU; Wistar random, SPF-bred rats were treated with 4-hydroxyphenethylammonium chloride (CAS no: 60-19-5) via oral gavage route.
Executive summary:

The oral toxicity study was conducted by using 4-hydroxyphenethylammonium chloride (CAS no: 60-19-5) in 20 male and femaleCpb:WU; Wistar random, SPF-bred rats at the dose concentration of 125 mg/kg, 250 mg/kg, 500 mg/kg , 1000 mg/kg and 2000 mg/kg bw. The given test chemical (purity 99%, obtained from E. Merck AG, Darmstadt, Germany)administered orally as a 25% aqueous dilution at various dose levels to groups of 2 male and 2 female rats.The exact amount of the test substances to be dosed in mg/kg was calculated for each animal and administered by gavage. The rats were observed for mortality and clinical signs for 14 days. The animals that died and the survivors killed after 14 days were examined for pathological changes.No mortality was observed at 2000 mg/kg bw. Most of the animals showed sluggishness and Piloerection. Exophthalmus was seen in the 1000 and 2000 mg/kg groups. Therefore, LD50 was considered to be >2000 mg/kg bw, when male and female Cpb:WU; Wistar random, SPF-bred rats were treated with 4-hydroxyphenethylammonium chloride via oral gavage route.