Dibutyl sebacate

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

10 Aug 1987 - 12 Jan 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Reference 2

Reference Type:

secondary source

Title:

Diesters Category of the Aliphatic Esters Chemicals (Test Plan and Robust Summaries for Substances in the HPV Test Plan)

Author:

US-EPA (American Chemistry Council's Aliphatic Esters Panel)

Year:

2010

Bibliographic source:

High Production Volume (HPV) Chemical Challenge Program (201-16837A and 201-16837B)

Reference 3

Reference Type:

secondary source

Title:

Bis(2-ethylhexyl)adipate (DEHA) CAS N°: 103-23-1

Author:

OECD

Year:

2000

Bibliographic source:

SIDS Initial Assessment Report for SIAM 10; Tokyo, Japan, 15-17 March 2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) adipate

EC Number:

203-090-1

EC Name:

Bis(2-ethylhexyl) adipate

Cas Number:

103-23-1

IUPAC Name:

bis(2-ethylhexyl) adipate

Details on test material:

- Name of test material (as cited in study report): Di-(2-ethylhexyl) Adipate (DEHA)
- Physical state: clear liquid
- Analytical purity: 99.2% w/w
- Batch No: Y02259/003/001
- Storage: in a ventilated cupboard at 20 ºC
- Stability: Chemical stability of DEHA in diet was determined on three batches of diet at nominally 300 and 12000 ppm. Satisfactory chemical stability was established for diet stored at room temperature for up to 34 days.

Test animals

Species:

rat

Strain:

other: Alpk:APfSD (WIstar-derived)

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on mating procedure:

- M/F ratio per cage: 1/2
- Length of cohabitation: 10 days
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy
- After 10 days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: no
- After successful mating each pregnant female was caged (how): individually
In all pairings brother sister mating was avoided.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

(P) Males: 10 weeks before mating.
(P) Females: 10 weeks before mating
After 10 weeks, the animals were mated to produce a single litter (F1A) which were reared to day 36 post partum.
Test diets were fed continuously throughout the study.

Frequency of treatment:

continuously

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
300, 1800 and 12000 ppm
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
304, 1038 and 11840 ppm
Basis:
other: analytical

Doses / concentrations 3

Remarks:

Doses / Concentrations:
approx. 52, 178 and 2102 mg/kg bw/day for males and 61, 203 and 2399 mg/kg bw/day for females
Basis:
other: The values were calculated by the mean body weights and the mean food consumption with the analytical compound values

No. of animals per sex per dose:

15 males
30 females

Control animals:

yes, plain diet

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

1

Dose descriptor:

NOAEL

Remarks:

fertility

Effect level:

>= 2 102 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: see 'Remark'

2

Dose descriptor:

NOAEL

Remarks:

fertility

Effect level:

>= 2 399 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: see 'Remark'

3

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

178 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: The nominal dose was 1800 ppm in diet.

4

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

203 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: The nominal dose was 1800 ppm in diet.

5

Dose descriptor:

LOAEL

Remarks:

systemic

Effect level:

2 102 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: The nominal dose was 12000 ppm in diet. An increase in liver weight was observed in both male and female parents receiving 12000 ppm DEHA.

6

Dose descriptor:

LOAEL

Remarks:

systemic

Effect level:

2 399 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: The nominal dose was 12000 ppm in diet. An increase in liver weight was observed in both male and female parents receiving 12000 ppm DEHA. Reduction in bodyweight gain during gestation in the 12000 ppm DEHA group compared with controls.

Results: F1 generation

Effect levels (F1)

1

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

178 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Mean pup weight gain and total litter weight were reduced at the highest dose. Litter size was slightly reduced throughout the post-partum period at the highes dose.

2

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

203 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Mean pup weight gain and total litter weight were reduced at the highest dose. Litter size was slightly reduced throughout the post-partum period at the highest dose.

3

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

2 102 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Mean pup weight gain and total litter weight were reduced. Slighly reduction in litter size throughout the post-partum period.

4

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

2 399 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Mean pup weight gain and total litter weight were reduced. Slighly reduction in litter size throughout the post-partum period.

Overall reproductive toxicity

Reproductive effects observed:

not specified