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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study does not comply with the specific testing guideline but the documented results are sufficient to be accepted.

Data source

Reference Type:
Effects of in utero or suckling exposure to cerium (citrate) on the postnatal development of the mouse
D'agostino RB, Lown BA, Morganti JB, Massaro EJ
Bibliographic source:
J Toxicol Environ Health 10:449-458

Materials and methods

Test guideline
no guideline followed
Principles of method if other than guideline:
Gravid female mice received a single subcutaneous dose of cerium citrate (80 mg Ce/kg) on day 7 or 12 of gestation, or on day 2 postpartum. Effects on body weight, activity and behavioral measurements were evaluated.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Cerium(3+) 2-hydroxypropane-1,2,3-tricarboxylate
EC Number:
EC Name:
Cerium(3+) 2-hydroxypropane-1,2,3-tricarboxylate
Cas Number:
cerium(3+) citrate
Constituent 2
Reference substance name:
Cerium citrate
Cerium citrate
Details on test material:
Cerium chloride (anhydrous powder, 99.9% pure on a rare-earth oxide basis) was obtained from Alfa products (Ventron Corporation, Danvers, Mass.). Sodium citrate was obtained from J. T. Baker Chemical Co. (Phillipsburg, N.J.). All chemicals were of the hightest grade available commercially. CeCl3 is insoluble at physiological pH. Thus, for purposes of administration, a 1:3 CeCl3:sodium citrate complex was prepared and adjusted to pH 7.4 with NaOH.
Sodium citrate (as the same concentration as in the Ce solution), adjusted to pH 7.4 with HCl, serve as the control solution.
Prior to administration, stock solutions were diluted and sterilized by autoclaving at 121°C at 20 psi for 30 min.

Test animals

Details on test animals or test system and environmental conditions:
Nullliparous Swiss ICR female mice (West Seneca Laboratories, West Seneca, N.Y.), 6 - 8 weeks old, were acclimated to laboratory conditions for a minimum of 2 weeks prior to breading.
All mice were housed in a thermostatically controlled room (22°C) and maintained on a 12h light cycle. Females were given free access to food (Charles River RMH 3000) and water during breeding, gestation and lactation.

Administration / exposure

Route of administration:
Details on exposure:
Experimental subjects received a single intrascapular subcutaneous dose ath the LD level of 80 mg Ce/kg in a constant injection volume (0.2 ml/30g maternal weight). Control animals received a quantity of citrate identical to that of the Ce citrate solution. The solutions were administered on d7 or 12 of gestation or on d2 after parturition.
Details on mating procedure:
Breeding was accomplished by daily housing, for 4h, of five females with a male. Successful matting was determined as the observation of a copulatory plug, which defined day 0 of gestation.
Doses / concentrations
Doses / Concentrations:
80 mg Ce/kg
nominal conc.
No. of animals per sex per dose:
40 females treated with cerium citrate
12 control females
Control animals:
yes, concurrent vehicle
Details on study design:
Immediately after parturition and before nursing occurred, litters were reduced to three males and three females, and distributed among mothers to form experimental groups. This procedure makes possible to differentiate effects on offspring resulting from exposure to Ce in utero, during suckling, or during both prenatal and postnatal development.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:not examined

Effect levels (maternal animals)

Dose descriptor:
Effect level:
80 mg/kg bw (total dose)
Basis for effect level:
other: other:

Results (fetuses)

Fetal abnormalities

not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

The developmental toxicity was evaluated as LOAEC = 80 mg/kg bw (total dose).
Executive summary:

It is postulated that ce is not transmitted to offspring via the milk of mothers exposed to ce citrate on d7 or 12 of gestation and therefore, an indirect effect of maternal intoxication must be considered.

In utero exposure to Ce citrate, administered maternally at the LD of 80 mg/kg on d7 or d12 of gestation, had no consistent effect on the adult behaviour of ce-exposed offspring.

The results of the present study suggest that ce is of relatively low toxicity to the developing organism.

The study reported that offspring of mice intravenously injected on gestation day 12 with a single dose of 80 mg/kg body weight cerium citrate had significantly reduced body weights in offsprings. The only significant behavioral effect in these pups was an increased rearing frequency. Other measures of activity, coordination, and simple learning were not affected, and were not further interpreted. One interesting observation was the decreased retrieval latency of foster mothers for pups exposed in utero relative to unexposed pups.