Dibutyl sebacate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Study period:

15 Sep - 16 Oct 1987

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:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

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
- Supplier: ICI France, Department Baleycourt
- Physical state: colourless liquid
- Batch: Y02259/003/003-4
- Analytical purity: 99.2% w/w
- Impurities (identity and concentrations): Phthalate (as DOP) 0.08% w/w

Test animals

Species:

rat

Strain:

other: Alpk:APfSD (Wistar derived)

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: not reported
- Length of cohabitation: overnight
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy

Successfully mated females were delivered to the experimental unit.
A total of 96 mated females was supplied over a two week period.

Duration of treatment / exposure:

days 1-22 of gestation.

Frequency of treatment:

Continuous feeding

Duration of test:

22 days

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 28, 170 and 1080 mg/kg bw/day
Basis:
other: approximately received doses (as given in study report)

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 300, 1800 and 12000 ppm
Basis:
nominal in diet

No. of animals per sex per dose:

24

Control animals:

yes, plain diet

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

ca. 170 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

LOAEL

Effect level:

ca. 1 080 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

3

Dose descriptor:

NOAEL

Effect level:

>= 1 080 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

4

Dose descriptor:

NOEL

Effect level:

ca. 28 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

5

Dose descriptor:

LOEL

Effect level:

ca. 170 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes. Remark: (non-adverse)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Table 1: Foetal defects and variants - Intergroup comparison of foetal defects and variants

	Dietary conc. of DEHA (ppm)
	0	300	1800	12000
No. of litters examined	24	23	24	23
External and visceral defects
No. of foetuses examined	282	263	278	243
No. of foetuses showing major defects	1	2	0	2
No. of foetuses showing minor defects only	7	8	9	3
Variants
No. of foetuses showing variants	69	69	81	78*
Skeletal defects
No. of foetuses examined	282	263	278	243
No. of foetuses showing major defects	7	0	1	1
No. of foetuses showing minor defects only	70	78	97**	120**
Variants
No. of foetuses showing variants	270	257	268	243**

 

Table 2: Summary of the type and incidence of major defects

	Dietary conc. of DEHA (ppm)
	0	300	1800	12000
External/Visceral
Situs inversus totalis	0	0	0	1
Left adrenal, kidney and ureter absent	1	0	0	0
Cysts attached to liver	0	1	0	0
Small right kidney	0	1	0	0
Umbilical hernia	0	0	0	1
Skeletal
Skull: Multiple minor defects	7	0	0	0
3^rdand 7^thribs (left) not ossified0	0	0	0	1
1^strib (right) partially ossified	0	0	1	0

 There was no evidence that the test substance is teratogenic to the rat at any of the dose levels tested (up to 12000 ppm -approximately 1000 mg/kg/day). Administration of 12000 ppm DEHA resulted in slight maternal toxicity and slight foetotoxicity.

At 1800 ppm, there was no evidence of maternal toxicity although minimal foetotoxicity was observed. A dietary level of 300 ppm DEHA was a clear no-effect level for embryonic development.