Glycine, N-methyl-N-(1-oxododecyl)-, 1-methylethyl ester

Endpoint summary

Description of key information

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).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

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

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

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

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

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

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

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

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

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

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

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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In a study with oral dosing of Wistar rats with up to 1000 mg/kg bw/day for 28 days, apart from changes in organ weights (liver, kidneys) no other significant adverse effects were noted (NOEL: 200 mg/kg bw/day). Therefore, there is no need for classification and labelling of the test item according to CLP Regulation 1272/2008/EG.