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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Principles of method if other than guideline:
- Short description of test conditions: The teratogenic effects of N-acetyl-L-tryptophan was investigated in JCL-ICR mouse.
The test substance was orally administered to pregnant mice at doses of 2.5 and 5 g/kg bw/day from GD 6 to 15. All F0-dams were autopsied to assess foetal parameters on GD 18.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
mouse
Strain:
ICR
Remarks:
JCR-ICR
Details on species / strain selection:
TEST ANIMALS
- Source: CLEA Japan, Meguro, Japan
- Age at study initiation: 12 - 13 weeks
- Diet: MF except for gestation and lactation period and NMF for gestation and lactation period, purchased by Oriental Yeast Co., Ltd, Japan, were given ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 5
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Justification for use and choice of vehicle (if other than water): Due to the low water solubility, CMC was used as vehicle for oral application.
- Concentration in vehicle: 1%
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
females: 10 days (from Day 6 to 15 of gestation (GD))
Frequency of treatment:
once a day
Doses / concentrationsopen allclose all
Dose / conc.:
5 000 mg/kg bw/day (nominal)
Dose / conc.:
2 500 mg/kg bw/day (nominal)
No. of animals per sex per dose:
20 females (control)
23 females (2500 mg/kg bw/day)
20 females (5000 mg/kg bw/day)
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: Doses were selected based on range-finding tests.
gavage: Based on a LD50 of 12500 mg/kg bw, a dose of 5000 mg/kg bw/day was selected as highest applied dose.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: every other day

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: every other day

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

Sacrifice and pathology:
GROSS PATHOLOGY and ORGAN WEIGHT: Yes. The animals were sacrificed on GD 18.
- Organs examined: brain, pituitary, thymus, heart, lungs, liver, kidneys, spleen, adrenals, ovaries

HISTOPATHOLOGY: No
Statistics:
Wilcoxon test: fetal mortality, number of fetus with external abnormalities, number of fetus with skeletal abnormalities except for ossification, number of fetus with visceral abnormallities, number of offspring with malformation and variation, number of live offspring, and postnatal differentiation
Chi-squared test: sex ratio, copulation ratio, pregnancy rate, delivering rate, and mortality
t test: other items

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
5 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: no adverse effects observed up to and including the highest dose level

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion