(S)-2,3-dihydro-1H-indole-2-carboxylic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Adequacy of study:

other information

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Version / remarks:

(Directive 84/449/EEC)

GLP compliance:

yes

Limit test:

no

Test animals

Species:

other: Rat, Wistar

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

propylene glycol

Duration of treatment / exposure:

Test duration: 90 days
Method of administration : gavage

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 5 mg/kg bw/day
Male: 5 animals at 25 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 600 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 5 mg/kg bw/day
Female: 5 animals at 25 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 600 mg/kg bw/day

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day

2

Dose descriptor:

NOEL

Effect level:

25 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Clinical observations:

- at 5, 25 and 50 mg/kg, no dose related clinical effects were observed.

- at 150 and 600 mg/kg: alopecia and rough coat, low body weight and body weigh gain, low food consumption during the first 2 weeks.

Laboratory findings:

- at 600 mg/kg: decreased albumin in males and females, increased gamma-glutamyl-transferase (CGT) in females only, increased alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) in males only.

- at 600 and 150 mg/kg: increaseed mean cell volume (MCV) in females only at 600 mg/kg, in males and females at 150 mg/kg, increased serum phosphate and decreased serum total protein in males and females.

- at 150 and 50 kg/mg: decreased red blood celle (RBC) in males and females.

- at 25 and 5 mg/kg: deviations from the normal values were not observed.

Effects in organs:

- at 600 mg/kg: macroscopic findings of a pale and discoloured appearance of the liver in 2/5 males, increased liver weights in males and females and decreased testes weights in males. Testicular changes of unhibited spermatogenesis, peripheral spermatid accumulation and the presence of multinucleated gaint cells in the tubular luminar.

- at 600 and 150 mg/kg: microscopic findings of hypertrophy of hepatocytes with associated diffuse fine vacuolation (at 150 mg/kg: males only). Congestion of the red pulp of the spleen was noted in 3/5 males at 600 mg/kg.

- at 600, 150 and 50 mg/kg: extramedullary haemopoiesis and increased heomosiderin pigment deposition in the spleen of males and females.

- at 25 and 5 mg/kg, no dose related effects to the spleen could be observed.

Applicant's summary and conclusion

Conclusions:

Classified as: Xn - Harmful