1,18-octadecanedioic acid

Repeated dose toxicity: oral

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

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,18-octadecanedioic acid

EC Number:

442-490-2

EC Name:

1,18-octadecanedioic acid

Cas Number:

871-70-5

Molecular formula:

C18H34O4

IUPAC Name:

octadecanedioic acid

Constituent 2

Reference substance name:

Octadecanedioic acid

EC Number:

617-978-5

IUPAC Name:

Octadecanedioic acid

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

1

Dose descriptor:

NOAEL

Effect level:

> 1 000

Based on:

test mat.

Sex:

female

Basis for effect level:

other: see 'Remark'

2

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.