L-Tyrosine, N-(aminocarbonyl)-3-methoxy-O,.alpha.-dimethyl-

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1990-1991

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Dust in air concentration determination is not reliable. Exact animal exposure can not be determined.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Principles of method if other than guideline:

Deviation from guideline: granulometry was not determined from the sample powder. Dust concentration in air was not measured by an approriate analitical method.

GLP compliance:

no

Test type:

other: acute inhalation toxicity sudy

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tyrosine, N-(aminocarbonyl)-3-methoxy-O,α-dimethyl-

EC Number:

608-271-2

Cas Number:

28861-00-9

Molecular formula:

C13H18N2O5

IUPAC Name:

Tyrosine, N-(aminocarbonyl)-3-methoxy-O,α-dimethyl-

Details on test material:

Name of test material (as cited in study report): Ureido-karbonsav
- Substance type: organic
- Physical state: white crystalline powder
- Stability under test conditions: stable
- Storage condition of test material: room temperature
- Other: sparingly soluble in water

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study: 12h
- Housing: 5-5 animals/cages
- Diet (e.g. ad libitum): LATI
- Water (e.g. ad libitum): ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 40-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12h/12 h

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
- Exposure chamber volume: 0.3 m3
- Method of holding animals in test chamber: connecting to glass tubes in a 40 cm wall
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols:
- Method of particle size determination:
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: calculation
- Samples taken from breathing zone: yes/no

VEHICLE
- Composition of vehicle (if applicable): DMSO
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not determined
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not determined

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

no

Remarks:

only calculation

Duration of exposure:

4 h

Concentrations:

ALC
29.2 mg/m3;
84.4 mg/m3;
136.7 mg/m3;

LC50
27.7 mg/m3;
83.3 mg/m3;
133.8 mg/m3

No. of animals per sex per dose:

10 males/10 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0; 1; 2; 3; 4; 7; 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, relative organ weights, histopathology

Results and discussion

Mortality:

No.

Clinical signs:

other: No.

Body weight:

Body weight gain of treated animals was smaller, than the untreated animals.

Gross pathology:

Slight changes in lungs.
Treated females liver and kidney relative organ weight was decreased.

Any other information on results incl. tables

Body weight change after treatment in gramm (g)

Males (average value, n = 10)

Dose (mg/m3)	0	1 day	2 day	3 day	4 day	7 day	14 day	Body weight increase (g)
133.8	245.0 +/-16.0	255.0 +/-13.0	270.6 +/- 13.7	275.0 +/- 13.0	276.0 +/- 8.4	293.7 +/- 13.0	300.6 +/- 11.4	+55.6
83.3	247.5 +/-26.9	247.5 +/-23.7	252.5 +/- 26.3	263.7 +/-15.4	278.1 +/- 24.0	294.3 +/- 24.1	300.6 +/- 24.7	+53.1
27.7	245.0 +/-16.4	243.1 +/-14.6	248.1 +/- 14.6	252.5 +/- 15.5	261.8 +/- 13.8	280.0 +/- 16.6	301.2 +/- 15.7	+56.2
Control	242.5 +/- 10.0	236.8 +/- 10.9	241.8 +/-10.3	254.3 +/- 11.7	259.3 +/- 12.0	288.7 +/- 12.4	303.1 +/- 13.6	+60.6
Control (untreated)	241.7 +/- 14.2	243.7 +/- 16.4	254.2 +/- 14.2	258.9 +/- 12.7	270.2 +/- 14.6	281.4 +/- 16.2	303.0 +/- 14.2	+61.3

Females (average value, n =10)

Dose (mg/m3)	0	1 day	2 day	3 day	4 day	7 day	14 day	Body weight increase (g)
133.8	199.3 +/-12.0	196.8 +/-13.8	208.9 +/- 14.8	208.1+/- 13.3	212.5 +/- 13.3	223.7 +/- 15.0	234.3 +/- 13.9	+35.0
83.3	187.5 +/-11.0	187.5 +/-12.8	186.6 +/- 12.2	185.6 +/-12.0	185.6 +/- 11.1	202.5 +/- 18.3	219.3 +/- 15.9	+31.2
27.7	188.1 +/-13.8	188.1 +/-13.8	191.8 +/- 14.3	198.7 +/- 13.8	201.8 +/- 12.7	219.3 +/- 13.7	227.5 +/- 12.2	+39.3
Control	194.3 +/- 15.6	201.8 +/- 11.3	201.8 +/-14.1	201.8 +/- 16.0	203.1 +/- 17.1	223.7 +/- 20.4	234.3 +/- 17.4	+40.0
Control (untreated)	192.4+/- 12.4	193.2 +/- 14.2	198.3 +/- 12.7	206.4 +/- 14.6	214.3 +/- 13.7	226.4 +/- 16.2	233.7 +/- 14.2	+41.3

 

Relative organ weight (100 g body weight) of male rats (average, n= 10)

Dose (mg/m3)	Brain	Liver	Kidney	Lung	Heart	Spleen	Thymus	Adrenal
133.8	0.51 +/-0.06	3.66 +/- 0.71	0.65 +/- 0.08	0.52 +/- 0.04	0.27 +/- 0.04	0.21 +/- 0.04	0.14 +/- 0.05	0.01 +/- 0.003
83.3	0.54 +/- 0.06	3.57 +/- 0.74	0.68 +/- 0.12	0.52 +/- 0.05	0.27 +/- 0.05	0.22 +/- 0.06	0.16 +/- 0.03	0.01 +/- 0.001
27.7	0.56 +/-0.04	3.68 +/- 0.36	0.64 +/- 0.03	0.52 +/-0.06	0.26 +/- 0.03	0.21 +/- 0.02	0.14 +/- 0.02	0.01 +/- 0.001
Control	0.62 +/-0.04	4.01 +/- 0.26	0.72 +/-0.02	0.51 +/-0.04	0.28 +/-0.01	0.26 +/-0.02	0.22 +/-0.03	0.002 +/-0.002
Control (untreated)	0.61 +/-0.05	4.05 +/- 0.19	0.72 +/-0.04	0.50 +/-0.03	0.28 +/-0.01	0.23 +/-0.02	0.17 +/-0.02	0.01 +/-0.001

Relative organ weight (100 g body weight) of female rats (average, n= 10)

Dose (mg/m3)	Brain	Liver	Kidney	Lung	Heart	Spleen	Thymus	Adrenal
133.8	0.61 +/-0.05	3.43 +/- 0.61	0.60 +/- 0.10	0.56 +/- 0.09	0.34 +/- 0.05	0.32 +/- 0.09	0.15 +/- 0.04	0.02 +/- 0.003
83.3	0.68 +/- 0.19	3.18 +/- 1.08	0.70+/- 0.05	0.67 +/- 0.15	0.31 +/- 0.06	0.24 +/- 0.05	0.16 +/- 0.06	0.03 +/- 0.001
27.7	0.63 +/-0.06	3.96 +/- 0.32	0.61 +/- 0.03	0.54 +/-0.05	0.29 +/- 0.02	0.24 +/- 0.03	0.13 +/- 0.02	0.03 +/- 0.001
Control	0.65 +/-0.06	4.15 +/- 0.45	0.68 +/-0.04	0.53 +/-0.06	0.28 +/-0.02	0.25 +/-0.04	0.20 +/-0.05	0.002 +/-0.001
Control (untreated)	0.66 +/-0.05	4.12 +/- 0.36	0.67 +/-0.04	0.52 +/-0.05	0.28 +/-0.02	0.23 +/-0.04	0.17 +/-0.03	0.01 +/-0.001

Applicant's summary and conclusion

Interpretation of results:

other: toxic effects can not be excluded

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The inhalation acute toxicity was not determined, because of analitycal problems of the test materials.
According to the observation of the animal studies inhalation toxicity can not be excluded.