Dimethyl isophthalate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study, no data on GLP

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl terephthalate

EC Number:

204-411-8

EC Name:

Dimethyl terephthalate

Cas Number:

120-61-6

Molecular formula:

C10H10O4

IUPAC Name:

dimethyl terephthalate

Test material form:

not specified

Test animals

Species:

rat

Strain:

Wistar

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: starch mucilage, 5 ml/kg body weight

Duration of treatment / exposure:

10 days, from gestation day 7 to 16.

Frequency of treatment:

once daily

Duration of test:

through mating and gestation, termination at day 21

Doses / concentrations

Remarks:

Doses / Concentrations:
1000 mg/kg body weight/day
Basis:

No. of animals per sex per dose:

20 females per treatment group

Control animals:

yes, concurrent vehicle

Details on study design:

Behaviour, general condition, food consumption and maternal body weight gain were checked during the study. The dams were sacrificed on day 21 of gestation, and caesarean section was performed and the numbers of corpora lutea, implantations, early and late resorptions, live and dead foetuses were determined. Placental weights and diameters of foetal resorptions were recorded. The pregnant females were necropsied and their organs macroscopically examined. The scope of foetal examinations encompassed determinations of sex, weight, crown-rump length, signs of life, appearance and externally visible abnormalities and, following appropriate preparation and staining, skeletal and visceral anomalies.

Examinations

Maternal examinations:

Behaviour, general condition, food consumption, placental and maternal body weight gain were checked during the study. The pregnant females were necropsied and their organs macroscopically examined.

Ovaries and uterine content:

The numbers of corpora lutea, implantations, early and late resorptions were assessed.

Fetal examinations:

The scope of foetal examinations encompassed determinations of sex, weight, crown-rump length, signs of life, appearance and externally visible abnormalities and, following appropriate preparation and staining, skeletal and visceral anomalies.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

1 000 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:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other:

Remarks on result:

other: No adverse effects were noted in any parameter at the single dose of 1000 mg/kg bw/d.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Foetuses obtained from the treated group were nomally developed and exhibited no externally visible abnormalities or variation or anomalies or variations of the internal organs or skeleton which could have been due to treatment with terephthalic acid dimethyl ester. The NOAEL was 1000 mg/kg body weight/d with regard to maternal toxicity and embryotoxicity/foetoxicity in the rat.

Applicant's summary and conclusion

Conclusions:

Dimethyl terephthalate, at 1000 mg/kg bw/d in a starch vehicle, was administered to female Wistar rats during gestation days 7 to 16. Treatment had no adverse effect on either general maternal health or intrauterine development. The NOAEL was 1000 mg/kg body weight/d for both maternal toxicity and embryotoxicity/fetoxicity. Data can be read-across to dimethyl isophthalate from DMTP, based on common functional groups. The substances are isomers. The similarities in structure are likely to apply to metabolites as well, with DMIP breaking down to isophthalic acid, just as DMTP is known to break down to terephthalic acid; these are isomers. Similar structures and similar break-down products for the two substances is the basis for the reading-across of data for this endpoint. This is adequate to fulfill the information requirements of Annex IX, to be the basis for classification and labelling decisions, and for risk assessment.