Registration Dossier

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes (incl. QA statement)
Remarks:
testing lab.
Limit test:
no

Test material

Constituent 1
Reference substance name:
Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide
EC Number:
600-026-8
Cas Number:
1000817-22-0
Molecular formula:
Unspecified
IUPAC Name:
Fatty acids, C8-18 and C18-unsatd., reaction products with diethanolamine and propylene oxide
Details on test material:
Name of test substance: Kerocom FM 38
Batch identification 2008250
Purity: 100% condensation product (BASF Project No. 08L00358)
Homogeneity: Homogeneous
Stability: The stability of the test substance under storage conditions over the test period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Physical state/appearance: liquid/yellow to brown, clear
Storage conditions: ambient (room temperature)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Age (at supplied); sex: 32-34 days; males and females
Identification: The rats were identified clearly by ear tattoo.
The rats were housed together (5 animals per cage) in H-Temp polysulfonate cages supplied by TECNIPLAST, Hohenpeißenberg, Germany (floor area about 2065 cm2). Bedding in the cages were Type Lignocel PS 14, dust-free bedding, supplied by SSNIFF, Soest, Germany. Motor activity measurements were conducted in polycarbonate cages with wire covers from Ehret, Emmendingen, Germany (floor area about 800 cm2) and small amounts of bedding material (Type Lignocel PS 14, see above). For enrichment, wooden gnawing blocks (Typ NGM E-022) were added, supplied by Abedd® Lab. and Vet. Service GmbH, Vienna, Austria.
The animals were accommodated in fully air-conditioned rooms in which central air conditioning guaranteed a range of temperature of 20-24 °C, a range of relative humidity of 30-70% and 15 air changes per hour. The day/night cycle was 12 hours (12 hours light from 06.00 h-18.00 h, 12 hours dark
from 18.00 h-06.00 h). The animal room was completely disinfected prior to the study using a disinfector ("AUTEX", fully automatic, formalin-ammonia-based terminal disinfector). The floor and the walls were cleaned once a week with water containing an appropriate disinfectant.
The food used was ground Kliba maintenance diet mouse/rat “GLP” meal, supplied by Provimi Kliba SA, Kaiseraugst, Switzerland. Food and drinking water (from water bottles) were available ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test substance was applied as a emulsion. To prepare this emusion, the appropriate amount of test substance was weighed out depending on the desired concentration. Then, drinking water was filled up to the desired volume and mixed by a magnetic stirrer. During administration of the test substance, preparations were kept homogeneous by stirring with a magnetic stirrer. The test-substance preparations were produced at least every 4th day a week.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 300, 1000 mg/kg b.w.
Basis:

No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
Food consumption and body weights were determined weekly. The animals were examined for signs of toxicity or mortality at least once a day. In addition, the animals were examined daily for any clinically abnormal signs before and after treatment. Detailed clinical examinations in an open field were conducted prior to the start of the administration period and weekly thereafter. Clinicochemical and hematological examinations as well as urinalyses were performed towards the end of the administration period.
Sacrifice and pathology:
After the administration period all animals were sacrificed and assessed by gross pathology, followed by histopathological examinations.
Other examinations:
A functional observational battery (FOB) as well as motor activity measurements were carried out at the end of the administration period.

Results and discussion

Results of examinations

Details on results:
Test group 3: 1000 mg/kg bw/d
Clinical Examinations
• Salivation after treatment was observed in all animals of both sexes on several days of the study.
Clinical Pathology
• No test substance-related findings were observed.
Pathology
• Focal squamous hyperplasia was observed in the forestomach of 1 male.
• Erosion/ulcer was observed in the forestomach (margo plicatus) of 1 male and 1 female.
• Minimal focal inflammation was observed in the forestomach (margo plicatus) of 1 male.

Test group 2: 300 mg/kg bw/d
Clinical Examinations
• Salivation after treatment was observed in all male and 3 female animals on several days of the study
Clinical Pathology
• No test substance-related findings were observed.
Pathology
• No test substance-related findings were observed.

Test group 1: 100 mg/kg bw/d
Clinical Examinations
• Salivation after treatment was observed in 1 male animal on study day 3.
Clinical Pathology
• No test substance-related findings were observed.
Pathology
• No test substance-related findings were observed.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
systemic effects
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: systemic toxicity (no systemic toxicity observed, highest dose tested)
Dose descriptor:
NOAEL
Remarks:
local effects
Effect level:
300 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: local effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In conclusion, with regard to pathological findings in the forestomach the oral administration of Kerocom FM 38 by gavage over a period of 4 weeks revealed only locally signs of toxicity in male and female Wistar rats at dose levels of 1000 mg/kg bw/d. This finding was related to the irritating potential of the test substance. Salivation was considered to be related to either the bad taste of the test substance or local affection of the upper digestive tract. This finding was not considered to be an adverse and toxicologically relevant effect.