Diisodecyl sebacate

Toxicity to reproduction

Administrative data

Endpoint:

multi-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

No data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study on a read-across compound, reported in the secondary literature (limited reporting). Only one (relatively low) dose level tested (about 10 mg/kg bw/day); screening reproduction/developmental screening limit tests use at least 1000 mg/kg bw/day.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1952

Report date:

1952

Reference 2

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1968

Report date:

1968

Reference 3

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Four-generation study, in which rats were treated via the diet with DOS at 200 mg/kg. Only one (relatively low) dose level tested (about 10 mg/kg bw/day). Abnormalities during parturition and nursing, and effects on growth, were assessed in the various generations.

GLP compliance:

no

Remarks:

predates GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dioctyl sebacate

EC Number:

219-411-3

EC Name:

Dioctyl sebacate

Cas Number:

2432-87-3

Molecular formula:

C26H50O4

IUPAC Name:

dioctyl sebacate

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): dioctyl sebacate
- Molecular formula (if other than submission substance): C26-H50-O4
- Molecular weight (if other than submission substance): 426.677
- Smiles notation (if other than submission substance): C(=O)(OCCCCCCCC)CCCCCCCCC(=O)OCCCCCCCC
- InChl (if other than submission substance): InChI=1S/C26H50O4/c1-3-5-7-9-15-19-23-29-25(27)21-17-13-11-12-14-18-22-26(28)30-24-20-16-10-8-6-4-2/h3-24H2,1-2H3
- Structural formula attached as image file (if other than submission substance): see Fig. 1
- Substance type: no data
- Physical state: no data
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on mating procedure:

- M/F ratio per cage: no data in citing sources
- Length of cohabitation: no data in citing sources
- Proof of pregnancy: no data in citing sources
- Further matings after two unsuccessful attempts: no data in citing sources
- After successful mating each pregnant female was caged (how): no data in citing sources
- Any other deviations from standard protocol: no data in citing sources

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4 generations

Frequency of treatment:

Presumably daily (given in the diet)

Details on study schedule:

No data in citing sources

Doses / concentrations

Remarks:

Doses / Concentrations:
200 mg/kg diet
Basis:
nominal in diet
equivalent to about 10 mg/kg bw/day for adult rats, and 20 mg/kg bw/day for young rats

No. of animals per sex per dose:

No data in citing sources

Control animals:

yes, plain diet

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

ca. 10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects seen over the course of the study

Remarks on result:

other: Generation: all generations (migrated information)

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOEL

Generation:

F1

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects observed at dose.

Remarks on result:

not determinable due to absence of adverse toxic effects

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Secondary sources report on a pre-GLP four-generation study on DOS, a structurally-related read-across compound for DIDS. Reproduction, suckling and growth were evidently normal in rats of the various generaitons recieving about 10 mg/kg bw/day from the diet (the study NOAEL).

Executive summary:

A pre-GLP four-generation study has been conducted on DOS, a structurally-related read-across compound for DIDS, and is reported in the secondary literature.

 

Rats were treated with a single (relatively low) dose level of 200 mg/kg diet (about 10 mg/kg bw/day) over four generations [no further details in citing sources; screening developmental/reproductive limit tests use a dose level of at least 1000 mg/kg bw/day].

 

Reproduction was considered normal, and no abnormalities were found during parturition or nursing. Growth was evidently normal in each generation. The no-observed-adverse-effect level for fertility effects can therefore be considered about 10 mg/kg bw/day.