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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:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Effects of ethylene glycol and metabolites on in vitro development of rat embryos during organogenesis
Author:
Klug, S., Merker, H.-J., Jäckh, R.
Year:
2001
Bibliographic source:
Toxicology in Vitro, Vol 15, p 635-642

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: WEC test (Whole Embryo Culture)
Principles of method if other than guideline:
Rat whole embryos were exposed to ethylene glycol and its metabolites, among which oxalic acid, for 48 hr (day 9.5-11.5 of gestation). Yolk sac diameter, crown-rump length, number of somites, and protein content of each embryo were evaluated. Additionally, embryos were assessed with help of a scoring system for the degree of differentiation, photographed and histologically examined.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Oxalic acid
EC Number:
205-634-3
EC Name:
Oxalic acid
Cas Number:
144-62-7
IUPAC Name:
oxalic acid
Details on test material:
Oxalic acid was obtained (as solid) from Merck-Schuchardt

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
other: in vitro (in the culture medium)
Vehicle:
other: culture medium
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Not applicable
Duration of treatment / exposure:
48 hr
Frequency of treatment:
continuous treatment
Duration of test:
48 hr
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
Control
Basis:

Remarks:
Doses / Concentrations:
1 mM
Basis:
nominal conc.
in culture medium
Remarks:
Doses / Concentrations:
2 mM
Basis:
nominal conc.
in culture medium
No. of animals per sex per dose:
Control: 38 embryos
1 mM: 16 embryos
2 mM: 19 embryos
Control animals:
yes, concurrent no treatment

Results and discussion

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Effect levels (fetuses)

Dose descriptor:
NOEC
Effect level:
< 1 other: mM
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

The following table is reproduced from the publication.

n

Yolk sac (mm)

Crown-rump length (mm)

Somites (n)

Protein (µg/E)

Score

%Dys

Control

38

4.70

3.74

27

214

37

0

4.47

3.57

26

188

36

4.31

3.42

25

165

35

1 mM

16

4.73

3.60

26

234

38

6

4.68

3.42*

26

193

36

4.23

3.32

25

178

35

2 mM

16

4.01

3.23

24

146

28

100

3.90**

3.00**

23***

136**

25**

3.60

2.61

22

120

22

At 1 mM, a significant reduction in the value for the crown-rump length was recorded. The 6% rate of dysmorphogenesis was within the range of historical controls. 2 mM oxalic acid induced severe dysmorphogenesis in 100% of the cultured embryos. Furthermore, all variables for growth and differentiation were significantly lower when compared to controls. The authors approximate the NOEC to be rather close to 1 mM.

Applicant's summary and conclusion

Conclusions:
Oxalic acid showed embryotoxic effects in vitro at a dose level of 2 mM, inducing severe dysmorphogenesis in 100% of the embryos and significantly lower growth and differentiation variables. At 1 mM, a significant reduction in the value for the crown-rump length was recorded, whereas all other variables were unaffected. The NOEC<1 mM, but based on these results, the authors approximate the NOEC to be rather close to 1 mM.
Executive summary:

Rat whole embryos were exposed to ethylene glycol and its metabolites, among which oxalic acid, for 48 hr (day 9.5-11.5 of gestation). Yolk sac diameter, crown-rump length, number of somites, and protein content of each embryo were evaluated. Additionally, embryos were assessed with help of a scoring system for the degree of differentiation, photographed and histologically examined.

Oxalic acid showed embryotoxic effects in vitro at a dose level of 2 mM, inducing severe dysmorphogenesis in 100% of the embryos and significantly lower growth and differentiation variables. At 1 mM, a significant reduction in the value for the crown-rump length was recorded, whereas all other variables were unaffected. The NOEC<1 mM, but based on these results, the authors approximate the NOEC to be rather close to 1 mM.