Registration Dossier

Administrative data

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

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: flakes
Details on test material:
Purity: 100% active matter
Remarks: White, solid.
Solubility: Poorly soluble (=< 2 mg/L in test medium).
Carbon chain length distribution: C16 2,98%, C18 92,9%, C18:1 1,04%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 mg test substance/kg bw
Basis:

No. of animals per sex per dose:
5
Control animals:
yes

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 1 000
Based on:
test mat.
Sex:
female
Basis for effect level:
other: see 'Remark'
Dose descriptor:
LOEL
Effect level:
> 1 000
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Practically nontoxic. The 28-day NOAEL for 1,18-octadecanedioic acid in rats is 1,000 mg/kg bw.

No significant differences in weight gain between the test- and controlgroups could be detected in female animals, on the 95% confidential level.
For the male HD group a marked reduced weight gain was observed, which also showed significant difference, on the 95% confidential level. This
finding is assumed to be compound-related. This finding was neither confirmed by histopathology nor any of the other evaluated parameters.
The mean weight gain in all groups was less as expected according to the standard growth curve for this strain. These diminished weight gains are due
to the daily treatment which is combined with mechanical manipulation and therefore with increased stress for the animals.
Upon histopathology the following treatment related findings were recorded:
Results:
There were no treatment-related changes.

Commentary:
There were two treated male rats with mild tubular degeneration of the kidneys and none in controls. The change was present unilaterally in both cases suggesting that these were fortuitous observations, not associated with treatment. The other occasional changes are those that are commonplace in young laboratory rats. The determination of clinical chemical pararneters revealed that all mean and mostindividual values (GOT, GPT, AP, TP, Urea, Crea, Na, K) were within the expected range. Single deviations are deemed to be of no toxicological relevance. There were no toxicologically relevant results in relative and absolute organ weight for both sexes and any ofthe groups.
In the assessment of the haematology-values (Hct, Hb, RBC, WBC, Platelets, aPTT) no changes of toxicological relevance were found. Compound-relation was not detectable.