Potassium hydrogen oxalate

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

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

Test material information

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
Control
Basis:

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1 mM
Basis:
nominal conc.
in culture medium

Doses / concentrations 3

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.