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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data are reliable but reference lacks details

Data source

Reference
Reference Type:
publication
Title:
Toxicological evaluation of Acetyltributylcitrate
Author:
Larionov AG & Cherkasova TE
Year:
1977
Bibliographic source:
Gig Sanit 4, 102 - 103

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of animals were provided feed containing a milk solution of the test substance (ATBC) at doses of 50 and 250 mg/kg for 12 months
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Name of test material (as cited in study report): Acetyl tributyl citrate (CAS NR 77-90-7)
Analytical purity: Not stated

Test animals

Species:
rat
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Diet (e.g. ad libitum): ad libitum
Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
Groups of animals were provided feed containing a milk solution of the test substance (ATBC) at doses of 50 and 250 mg/kg for 12 months
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
In the 9th month of the study, a cross-mating of the animals was performed, male gonads were evaluated and embryotoxic effects were examined. The following indicators of embryotoxic effects were evaluated:
early and late embryonic death (determined by examining the numbers of corpora lutea and implantation sites)
number of normal, resorptive and deformed tissues
Duration of treatment / exposure:
12 months
Frequency of treatment:
continuously via diet
Duration of test:
12 months
Doses / concentrations
Remarks:
Doses / Concentrations:
50 or 250 mg/kg
Basis:
nominal in diet
No. of animals per sex per dose:
1 replicate per dose, rest not reported
Control animals:
yes, concurrent no treatment

Examinations

Maternal examinations:
Clinical signs, mortality, size and weight of the placenta
Fetal examinations:
early and late embryonic deaths (examining the numbers of corpora lutea and implantation sites)
number of normal, resorptive and deformed tissues
length of newborns
ear and eye openings, appearance of body hair and teeth, behaviour; and body weight
Statistics:
Not reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
50 mg/kg: no adverse effects
250 mg/kg: increases in body weight, length of the progeny and placental weight
No differences concerning fertility rate and number of pups born/pregnant female.
There were no significant effects on male gonads and at 250 mg/kg the spermatogenesis index was comparable with controls.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOEL
Effect level:
50 mg/kg bw/day (nominal)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOEL
Effect level:
250 mg/kg bw/day (nominal)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
No adverse effects on eye and ear opening, body fur and incisor appearance.
No effects on behaviour and body weights.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Dosing with ATBC via diet over 12 months had no effects to male sexual cells, caused no embryotoxic effects and had no impact on the development in offspring.
Executive summary:
A Toxicological evaluation of Acetyltributylcitrate [Larionov AG & Cherkasova TE, 1977; cited in US EPA (2004) High Production Volume (HPV) Chemicals Challenge Program: Assessment of Data Availability and Test Plan for Acetyl Tributyl Citrate (ATBC) (CAS NR 77-90-7)] has been carried out as follows: Groups of rats were dosed with a milk solution of ATBC via diet at nominal doses of 50 and 250 mg/kg over 12 months. A cross-mating of the animals was performed. In the 9th month of the study, gonads were evaluated and the animals were evaluated for embryotoxic effects. The dosing caused no significant effects on male sexual cells, no embryotoxic effects and there also were no adverse effects on growth and foetal/litter development in the offspring. It can be assumed that the same applies to tributyl citrate (CAS 77-94-1) as it is a near analogue to the test substance acetyl tributyl citrate.