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Administrative data

Description of key information

Oral, (10-day developmental toxicity study): LD50 > 5000 mg/kg bw

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
The dose administered for ten consecutive days was higher than the limit dose recommended in the current OECD guideline. Therefore it is considered justified to use the available data and avoid generating additional in vivo data.
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
Short description of test conditions: The developmental toxicity study of N-acetyl-L-tryptophan was conducted in Wistar rats. N-acetyl-L-tryptophan was administered orally at doses of 2500 and 5000 mg/kg bw/day from GD 7 to 17. The animals were observed for mortality/morbidity and evidence of clinical signs. For all animals, the body weights were recorded and a necropsy was performed.
GLP compliance:
no
Test type:
other: Developmental toxicity study
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): due to the low water solubility, CMC was used as the vehicle
- Concentration in vehicle: 1%
Doses:
2500 and 5000 mg/kg bw/day
No. of animals per sex per dose:
21, 22 and 20 females (control, 2500 and 5000 mg/kg bw/day)
Control animals:
yes
Details on study design:
N-acetyl-L-tryptophan was administered orally at doses of 2500 and 5000 mg/kg bw/day from GD 7 to 17.
- Frequency of observations and weighing: Animals were observed for clinical signs or morbidity every second day. The body weight was recorded on GD 0, 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20. The food consumption was recorded on GD 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20.
- Necropsy of survivors performed: On day 20 of gestation the animals were sacrificed.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
5000 mg/kg bw/day: 1/20 dams died from pneumonia. This is considered to be an incidental occurrence.
Clinical signs:
No clinical signs of toxicity were observed during the study period.
Body weight:
The body weight gain during gestation was significantly decreased (35%) in the 5000 mg/kg bw/day group compared with the control group. Food consumption was significantly decreased in the 2500 and 5000 mg/kg bw/day dose groups (9 and 15%, respectively).
Gross pathology:
The necropsy revealed no treatment-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study from a reference substance with the same structure and similar intrinsic properties. Read-across is justified based on stereoisomerism. Source and target substance differ only in the three-dimensional orientations of their atoms in space (refer to analogue justification for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

There are no available data assessing the acute oral, inhalation and dermal toxicity potential of N-acetyl-DL-tryptophan (CAS 87-32-1). The assessment of acute toxicity was therefore based on studies conducted with a source substance (N-acetyl-L-tryptophan (CAS 1218-34-4)) as part of a read across approach, which is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.5. Structural similarities and comparable toxicokinetic properties of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute Oral toxicity

CAS 1218-34-4

There is no available acute oral toxicity data on the source substance. Therefore, available data from a, developmental toxicity study performed with N-acetyl-L-tryptophan was used to cover the endpoint. The dose administered for 10 consecutive days was higher than the limit dose recommended in the current OECD guideline and it is therefore considered justified to use the available data, and avoid generating additional in vivo data. Twenty pregnant female rats/dose were administered test substance in 1% carboxymethylcellulose at doses levels of 2500 and 5000 mg/kg bw/d from day 7 to 17 of gestation. The control group received the vehicle only. On gestation day 20, the dams were sacrificed. One dam in the 5000 mg/kg bw/day dose group died of pneumonia. This is considered to be an incidental occurrence. No clinical signs were observed during the study period. A decrease (35%) in body weight gain was observed in the 5000 mg/kg bw/day group when compared with the control group. The food consumption was significantly decreased in the 2500 and 5000 mg/kg bw/day dose groups compared with the control group (9 and 15%, respectively). Based on these results, the LD50 value was > 5000 mg/kg bw.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to N-acetyl-DL-tryptophan, data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

 

Therefore the available target and source substance data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

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