Reaction products of tetrabromophthalic anhydride with 2,2'-oxydiethanol and methyloxirane

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

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

Adequacy of study:

key study

Study period:

1979 - 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Experimental data from published sources and summaries from the OECD SIDS program are available for read-across.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Tetrabromophthalic anhydride [CASRN 632-79-1] Review of the toxicological literature.

Author:

Tice

Year:

1999

Bibliographic source:

http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Tetrabromophthalic.pdf, pp. 1-15

Reference 2

Reference Type:

publication

Title:

Bioassay of phthalic anhydride for possible carcinogenicity CAS No. 85-44-9

Author:

Anonymous

Year:

1979

Bibliographic source:

National Cancer Institute, Carcinogenesis, Technical Report Series No. 159, pp. 1-107

Reference 3

Reference Type:

publication

Title:

Toxicokinetics of phthalic acid: the common final metabolite of phthalic acid esters in rats

Author:

Lim et al.

Year:

2007

Bibliographic source:

JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, PART A, Vol. 70, pp. 1344-1349

Reference 4

Reference Type:

publication

Title:

NTP Technical Report on the Toxicology and Carcinogenesis Studies of Diallylphthalate (CAS No. 131-17-9) in F344/N Rats (Gavage Studies)

Author:

Anonymous

Year:

1985

Bibliographic source:

NATIONAL TOXICOLOGY PROGRAM TECHNICAL REPORT SERIES NO. 284, pp. 1-154

Reference 5

Reference Type:

publication

Title:

OECD SIDS 1,2-Dihydroxypropane CAS: 57-55-6

Author:

Anonymous

Year:

2001

Bibliographic source:

UNEP PUBLICATIONS, pp. 1-166.

Reference 6

Reference Type:

publication

Title:

OECD SIDS Initial Assessment Profile for Ethylene Glycols Category, pp. 1-4.

Author:

Anonymous

Year:

2004

Bibliographic source:

http://cs3-hq.oecd.org/scripts/hpv/ChemGroup.asp

Reference 7

Reference Type:

publication

Title:

Toxicological profile for di(2-ethylhexyl) phthalate

Author:

Anonymous

Year:

2002

Bibliographic source:

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, PUBLIC HEALTH SERVICE, AGENCY FOR TOXIC SUBSTANCES AND DISEASE REGISTRY, pp. 1-291

Reference 8

Reference Type:

publication

Title:

Proposed OPPTS science policy: PPARa-mediated hepatocarcinogenesis in rodents and relevance to human health risk assessments

Author:

Anonymous

Year:

2003

Bibliographic source:

OFFICE OF PREVENTION, PESTICIDES & TOXIC SUBSTANCES, U.S. ENVIRONMENTAL PROTECTION AGENCY, Washington, D.C. 20460, pp. 1-39.

Reference 9

Reference Type:

publication

Title:

Peroxisome proliferation and its role in carcinogenesis: Views and expert opinions of an IARC working group, Lyon, 7-11 December 1994,

Author:

Anonymous

Year:

1994

Bibliographic source:

IARC TECHNICAL PUBLICATION NO. 24, http://monographs.iarc.fr/ENG/Publications/techrep24/IARCrep24.pdf

Reference 10

Reference Type:

publication

Title:

OECD SIDS Initial Assessment Profile for High Molecular Weight Phthalate Esters (HMWPE) Category, pp. 1-6

Author:

Anonymous

Year:

2004

Bibliographic source:

http://cs3-hq.oecd.org/scripts/hpv/ChemGroup.asp

Materials and methods

Type of study / information:

See attached background material.

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: see attached document

Principles of method if other than guideline:

See attached background material.

GLP compliance:

yes

Remarks:

for certain of the studies

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-hydroxyethoxy)ethyl 2-hydroxypropyl 3,4,5,6-tetrabromophthalate

EC Number:

243-885-0

EC Name:

2-(2-hydroxyethoxy)ethyl 2-hydroxypropyl 3,4,5,6-tetrabromophthalate

Cas Number:

20566-35-2

Molecular formula:

C15H15Br4O7 (one ring component) C8 H2 Br4 O4 . C4 H10 O3 . C3 H8 O2 Unspecified reaction product of the three components

IUPAC Name:

2-(2-hydroxyethoxy)ethyl 2-hydroxypropyl 3,4,5,6-tetrabromophthalate

Details on test material:

See attached background material for the identities of the structural analogues.

Results and discussion

Any other information on results incl. tables

See attached background material.

Applicant's summary and conclusion

Conclusions:

The registered UCVB substance is not acutely toxic or irritating to the skin or eyes. Repeated dose studies on structural analogues show a lack of toxicity by the oral, dermal and inhalation routes. Neither prenatal developmental toxicity nor effects on reproductive organs was seen. A carcinogenicity study was negative.

Executive summary:

Acute mammalian data on the UVCB substance indicates it is not acutely toxic or irritating to the skin or eyes. Repeated dose toxicity was estimated from structural analogs, tetrabromophthalic anhydride, phthalic anhydride, and 1,2 -benzendedicarboxylic acid, 3,4,5,6 -tetrabromo-,bis(2 -ethylhexyl) ester.

Tetrabromophthalic anhydride, rapidly hydrolyzed to tetrabromphtalic acid following ingestion, did not cause developmental toxicity to rats at doses up to 3000 mg/kg/d adminstered from gestation days 6 -15. Tetrabomophthalic anhydride did not induce systemic toxicity at doses of 5000 mg/kg dermally, 5 d/wk, for 4 wks. Inhalation exposures up to 8 mg/L for 4 hr/d, 5 d/wk, 3wk, did not induce systemic toxicity.

The 7 wk NOAEL for phthalic anhydride in the rat and mouse was 12500 ppm in the diet. Phthalic anydride produced no evidence of carcinogenicity in rats and mice at doses up to 12500 ppm in the diet. No effect on reproductive organs was observed.

The 28-d NOAEL for 1,2 -benzendedicarboxylic acid, 3,4,5,6 -tetrabromo-,bis(2 -ethylhexyl) ester in the rat was 2000 ppm in the diet.