Registration Dossier

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 23 May 2007 and 27 November 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study (OECD TG421)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: white crystalline solid
- Supplier: Yuki Gosei Kogyo Co. Ltd.
- Lot No.: 075008
- Purity: 99.8%
- Impurities (identity and concentrations): ammonia (%): <0.1, Chloride (%): <0.02, Sulfates (%): <0.05, Residue on ignition (%): 0.02

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: (P) x 8 wks
- Weight at study initiation: (P) Males: 283 - 361 g; Females: 169 - 219 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 ℃
- Humidity (%): 55 ± 15 %
- Air changes (per hr): 15 air changes/hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark /12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: 14 days (maximum)
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
(P) Male: 42 days (from 14 days before mating to the day before sacrifice through the mating period)
(P) Female: 42 - 45 days (from 14 days before mating to 4 days after delivery through the mating and gestation periods)
Frequency of treatment:
once per day
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 40, 200, 1000 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
10 animals/sex/dose
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
Estrous cyclicity (parental animals):
No
Sperm parameters (parental animals):
Parameters examined in P male parental generations:
testis weight, epididymis weight
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: No

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number of pups, sex ratio, live births index, viability index, clinical condition, body weights, surface righting reflex

GROSS EXAMINATION OF DEAD PUPS: Yes
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals
- Maternal animals: All surviving animals

GROSS NECROPSY: Yes

HISTOPATHOLOGY: Yes (control and 1000 mg/kg/day groups)
- Histopathological examined organ:
Coagulating gland, Epididymides, Ovaries, Pituitary, Prostate, Seminal vesicles, Testes, Uterus/Cerivix, Vagina

ORGAN WEIGHTS: Yes (All groups of the male)
- Weighted organ:
Epididymides, Testes
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring were sacrificed on PND 5.
- These animals were subjected to macroscopic examination as follows:

GROSS NECROPSY: Yes
- Gross necropsy consisted of external and internal examinations.

HISTOPATHOLOGY / ORGAN WEIGTHS: No
Statistics:
Statistical analyses were conducted by Levene's test, one-way ANOVA, Dunnett’s test, Kruskal-Wallis ANOVA ,and Mann-Whitney U-test
Reproductive indices:
- Pre-coital interval (days)
- Mating index (%) = (Number of animals mated/number of animals paired) x 100
- Pregnancy index (%) = (Number of pregnant females/ Number of animals mated) x 100
- Gestation length
- Parturition index(%)= (Number of females delivering live offspring/ number of pregnant females) x 100
- % pre-implantation loss = (Number of corpora lutea - number of implantation sites/ number of corpora lutea) x 100
- % post - implantation loss = (Number of implantation sites - total number of offspring born/number of implantation sites) x 100
- Live birth index(%) = (Number of offspring alive on day 1/number of offspring born) x 100
- Sex ratio = (Number of male offspring/number of offspring of determined sex) x 100
Offspring viability indices:
Viability index (%) = (Number of offspring alive on day 4/number of offspring alive on day 1) x 100

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Reproductive function / performance (P0)

Reproductive function: estrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: The oral administration of beta-alanine to rats for a period of up to forty-five days at dose levels of up to 1000 mg/kg/day did not show any treatment-related effects at any dose level.

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not examined

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion