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Diss Factsheets

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001 - 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Version / remarks:
27-07-1995
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Specific details on test material used for the study:
Identity: ISOPROPYL N-LAUROYLSARCOSINATE
Description: pale yellow liquid
Batch number: 002013
Purity: 92.9 %
Stability of test item: stable under storage conditions
Expiry date: 31-03-2003

Test animals

Species:
rat
Strain:
Wistar
Remarks:
HanBrl:WIST (SPF)
Details on species / strain selection:
Rationale: Recognized by the international guidelines as a recommended test system
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test system: Rat, HanBrl: Wist (SPF)
Source: RCC Ltd., Füllinsdorf / Switzerland
Number of animals: 5 m / 5 f per group
Age when treated: ca. 7 weeks
Body weight: 112 - 159 g
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Husbandry
Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with target ranges for temperature 22 +/- 3°C and for relative humidity between 30-70 %. 12 hours fluorescent light/12 hours dark, music during the light period.
Accommodation: Groups of five in Makrolon type-4 cages
Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet ad libitum
Water: Community tap-water

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
Dosing volume: 5 mL/kg bw
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on oral exposure:
The test item formulations were prepared weekly and the test item was weighed into a glass beaker on a tared Mettler balance and the vehicle added. The mixtures were prepared using a magnetic stirrer and stored at room temperature (17-23°C). Homogeneity of the test item in the vehicle was maintained during the daily administration period using a magnetic stirrer.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Concentration, homogeneity and stability (after 2 hours and 7 days) of the dose formulations were determined in samples taken after experimental start. Concentration and homogeneity of the dose formulations were determined in samples taken during week 3 of the treatment.
Duration of treatment / exposure:
28 days
Frequency of treatment:
Once per day on 7 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (actual dose received)
Dose / conc.:
50 mg/kg bw/day (actual dose received)
Dose / conc.:
200 mg/kg bw/day (actual dose received)
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
5 m / 5 f per dose group
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
Mortality / Viability: twice daily
General cage-side observations: once before commencement of administration, twice daily on days 1-3 as well as once daily on days 4-28
Detailed clinical observations: in random sequence once before commencement of administration and once weekly (weeks 1-3) thereafter
Food consumption: once during the pre-test period and weekly thereafter
Body weights: weekly during pretest, treatment and before necropsy
Functional observational battery: during week 4
Clinical chemistry: at study termination
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Dunnett-test, Steel-test, Student's t-test and Fisher's exact-test

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:
no effects observed
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Test item-related changes in organ weight were noted as increased kidney weights in females treated with 1000 mg/kg/day and livers of both sexes treated with 1000 mg/kg/day. The weights of the all other organs were considered to be unaffected.
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels

Key result
Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
organ weights and organ / body weight ratios

Target system / organ toxicity

Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
1 000 mg/kg bw/day (actual dose received)
System:
hepatobiliary
Organ:
other: increased liver weights in high-dosed males and females
Treatment related:
yes
Dose response relationship:
no
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
From a study with oral administration of the test item to Wistar rats over 28 days, 200 mg/kg bw/day was established as the no-observed-effect-level (NOEL).
Executive summary:

Oral administration of the test item to Wistar rats at doses of 0, 50, 200 or 1000 mg/kg bw/day for 28 days resulted in no changes in mortality rates, no clinical signs, no changes in the parameters of the functional observation battery (including grip strength and locomotor activity), no differences in food consumption or body weight, no effects upon haematology or clinical biochemistry parameters, no macroscopic findings and no microscopic findings.

Treatment-related findings were generally restricted to increases in liver weights of males and females treated with 1000 mg/kg bw/day and increases in kidney weights of females treated with 1000 mg/kg bw/day.

Based on the results of this study, 200 mg/kg bw/day was established as the no-observed-effect-level (NOEL).