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Description of key information

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:
2006-11-27 to 2007-02-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 423 (adopted 2001)
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Strain: Hsd:Sprague-Dawley SD
Source: Harlan Italy S.r.l.
Body weight: 176 – 200 g
Age: ca. 6 - 8 weeks
Acclimatisation period: at least 5 days
Housing: in groups of 3, polycarbonate cages, equipped with a stainless steel mesh lid and floor
Diet: laboratory rodent diet (4 RF 18) ad libitum throughout the study except for an overnight fast prior to dosing and a period of approximately 4 hours after dosing
Water: ad libitum

Environmental conditions
Temperature (°C): 22 ± 2
Relative humidity (%): 55 ± 15
Photoperiod (hrs dark / hrs light): 12 / 12 by fluorescent tubes
Air changes (per hr): 15-20
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5%
Details on oral exposure:
The test item was formulated for dosing by suspension in 0.5% aqueous solution of carboxymethylcellulose to give a concentration of 200 mg/mL.
Dose volume: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Two groups with 3 females each were tested
Control animals:
no
Details on study design:
Animals were fasted overnight prior to dosing and food was made available approximately 4 hours after dosing.
Mortality and morbidity: Throughout the study all animals were checked twice daily.
Clinical signs: Animals were observed for clinical signs immediately upon dosing, approximately 30 min, 2 and 4 hours after dosing and daily thereafter for a total of 14 days.
Body weight: All animals were weighed at allocation to the study (day -1), immediately prior to dosing (day 1) and on days 2, 8 and 15.

All animals were killed on day 15 and were subjected to a gross necropsy examination for both external and internal abnormalities. The cranial, thoracic and abdominal cavities were opened to allow examination of their contents. Larger organs were sectioned. Both the stomach and representative sections of the gastro-intestinal tract were opened for examination of the mucosal surfaces.
Statistics:
not further specified
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
In trial 1, clinical signs were limited to piloerection seen on the day of dosing at the 2 and 4 hour post-dose observations.
In trial 2, piloerection, hunched posture and reduced activity were observed in the animals on the day of dosing.
Complete recovery occurred by day 2.
Body weight:
No adverse effects in both trials
Gross pathology:
No abnormalities found at termination
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of L-tryptophan feed grade was investigated in a GLP study according to OECD guideline 423. Two groups of 3 female Sprague-Dawley rats were dosed with 2000 mg/kg bw and observed for a period of 14 days. No mortality occurred. In trial 1, clinical signs were limited to piloerection seen on the day of dosing at the 2 and 4 hour post-dose observations. In trial 2, piloerection, hunched posture and reduced activity were observed in the animals on the day of dosing. Complete recovery occurred by day 2. Changes in body weight were within the expected range for this strain and age of animals. No abnormalities were observed at necropsy examination at termination of the study. From this study a LD50 value of > 2000 mg/kg bw can be derived.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
LD50 value: > 2000 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:
2008-03-12 to 2008-04-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 403 (adopted 1981)
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
traditional inhalation LC50 study
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Source: Charles River Deutschland GmbH, Sulzfeld, Germany
Age at study initiation: 8 – 9 weeks at time of administration
Body weight: 229 - 322 g before exposure
Housing: single caging in Makrolon type III cages; wire mesh lids
Diet: Ssniff R/M-H maintenance diet ad libitum
Water: tap water, ad libitum
Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
Temperature (°C): 21.7-24.3
Humidity (%): 46.2-64.9
Air changes (per hr): 12
Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposure apparatus: exposure chamber from TSE, Technical & Scientific Equipment GmbH, Germany
Exposure chamber volume: 19 L
System of dust generating: dust generator Technical & Scientific Equipment GmbH, Germany
Method of particle size determination: cascade impactor
Rate of air: 700 L/h
MMAD: 3.1 um
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Measurement by gravimetric analysis. Dust was collected 12 times during exposure period. The exact amount of collected air was measured by a gas meter.
Duration of exposure:
4 h
Concentrations:
Target concentration: 5 mg/L
Actual concentration of the dust: 5.17 mg/L
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: 1 - 6 hours after the start of exposure and daily thereafter
Frequency of weighing: day 0 and on days 7 and 14 following administration
Necropsy of survivors performed: yes
Other examinations performed: clinical signs, body weight
Statistics:
Means and standard deviations of each test group were calculated for body weight and body weight gain. Median was calculated for environmental condition in the animal room. The particle size distribution was statistically evaluated based on probit analysis. As a limit test was performed, no calculation of the LC50 was possible.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.17 mg/L air
Exp. duration:
4 h
Mortality:
No mortality.
Clinical signs:
other: All animals were normal during the whole 14-day observation period
Body weight:
Mean body weights: Prior to study: 322 g (males) and 229 g (females); End of study: 407 g (males) and 252 g (females)
Mean weight gain: days 0-7: 38.4 g (males) and 5.4 g (females); days 7-14: 45.8 g (males) and 18.0 g (females)
Two females lost weight in the first week after exposure
Gross pathology:
Nothing abnormal was seen in any of the animals
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
L-tryptophan feed grade was tested in a GLP study according to OECD guideline 403. The 4h-inhalation exposure of male and female Sprague-Dawley rats at a concentration of 5.17 mg/L gave no indications for adverse effects. Therefore, the 4h-LC50 is greater than 5.17 mg/L air.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 170 mg/m³
Quality of whole database:
LC50 value: > 5170 mg/m3

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The acute oral toxicity of L-tryptophan was investigated in a GLP study according to OECD guideline 423. Two groups of 3 female Sprague-Dawley rats were dosed with 2000 mg/kg bw and observed for a period of 14 days. No mortality occurred. In trial 1, clinical signs were limited to piloerection seen on the day of dosing at the 2 and 4 hour post-dose observations. In trial 2, piloerection, hunched posture and reduced activity were observed in the animals on the day of dosing. Complete recovery occurred by day 2. Changes in body weight were within the expected range for this strain and age of animals. No abnormalities were observed at necropsy examination at termination of the study. From this study a LD50 value of > 2000 mg/kg bw can be derived.

L-tryptophan feed grade was tested in a GLP study according to OECD guideline 403. The 4h-inhalation exposure of male and female Sprague-Dawley rats at a concentration of 5.17 mg/L gave no indications for adverse effects. Therefore, the 4h-LC50 is greater than 5.17 mg/L air.

Justification for classification or non-classification

Due to the effect levels obtained in the acute toxicity studies, no classification according to EU and GHS criteria is required.