Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given (with respect to embryotoxic and teratogenic effects)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
A study of embryotoxic and teratogenic action of some industrial substances formed during production of dimethylterephthalate
Author:
Krotov YA & Chetobar NA
Year:
1972
Bibliographic source:
Gig. Truda Prof. Zabol, Vol. 16, 40-43
Report Date:
1972

Materials and methods

Principles of method if other than guideline:
Developmental toxicity study
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: vapour
Details on test material:
- Name of test material (as cited in study report): paratoluic methylate (PTE)

Test animals

Species:
rat
Strain:
other: white

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
no data
Duration of treatment / exposure:
24 h per day for 20 days
Frequency of treatment:
daily
Duration of test:
20 days
Doses / concentrations
Remarks:
Doses / Concentrations:
150 mg/m3
Basis:
nominal conc.
No. of animals per sex per dose:
29 pregnant females
Control animals:
yes, concurrent no treatment

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
LOAEC
Effect level:
150 mg/m³ air (nominal)
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
LOAEC
Effect level:
150 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: embryotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Increased pre- and postimplantation losses (preimplantation losses of 32,9 % and 11.3 %; percentage of postimplantation losses: 49.3 % vs. 4.8 % in controls). The authors considered pre- and postimplatation losses of 20 % and 15 % as normal values.

Few gross and microscopic alterations (e.g. shortened tail, adactylia, cryptorchism, hydronephrosis) were observed, but were considered to be sponaneous effects (only offspring of a single dam was affected, or incidences were comparable to control group)

Maternal effects of the study were not stated, but effects in former examinations at "similar exposure concentrations" were reported: altered activity of cholinesterase, altered chronaxy, blood proteins and histomorphology (no further details)

A further study with single 24 h exposure to 750 mg/m3 on gestation day (GD) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 revealed no embryotoxic or teratogenic effects. A total of 10 maternal animals died on GD 5, 6, 7, 8, 10 and 13.

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, embryotoxic effects were oberved at maternal toxic exposures and are therefore considered to be secondary effects to maternal toxicity. The exposure did not produce other developmental effects including teratogenicity.