Cobalt(2+) hydrogen citrate

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented study which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Effects of Cobalt on Postnatal Development and Late gestation in Rats Upon Oral Administration

Author:

Domingo, J.L. et al.

Year:

1985

Bibliographic source:

Revista Espanola de Fisiologia 41: 293-298

Materials and methods

Principles of method if other than guideline:

4 groups of pregnant rats are administered different doses of the test substance from gestation day 14 to day 21 of lactation. The dams, the offspring and litter parameters are examined to determine the effect of the test substance on late fetal development, labour and delivery, lactation, neonatal viability, and growth and development of the newborn.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

cobalt (II) chloride

IUPAC Name:

cobalt (II) chloride

Details on test material:

- Name of test material (as cited in study report): cobalt (II) chloride
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Biocentre (Barcelona, Spain)
- Housing: before study initiation 5 females and 2 males were kept per cage
- Diet: Panlab-diet, Barcelona, Spain; ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Humidity (%): 55 ± 5

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 5/2
- Length of cohabitation: no data
- Proof of pregnancy: sperm in vaginal smear day 0 of pregnancy

Duration of treatment / exposure:

day 14 of gestation to day 21 of lactation
(overall approx. 28 days)

Frequency of treatment:

daily

Duration of test:

sacrifice on day 21 of lactation

Doses / concentrations

Remarks:

Doses / Concentrations:
12, 24, 48 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

15 pregnant females

Control animals:

not specified

Details on study design:

- Dose selection rationale: The doses correspond to 1/10, 1/20 and 1/40 of the oral LD50 value.

Examinations

Maternal examinations:

no data

Ovaries and uterine content:

Parameters examined:
- Number of litters
- Number of living and dead young
- Male-female ratio
- Average body weight by litter

Fetal examinations:

Offspring examinations:
- Survival ratio
- Mortality, body weight gain and general symptoms: day 1, 4 and 21
- Examination for external malformations, body and tail length: day 1, 4 and 21
- Gross pathology: gross external and internal examination at the end of the study (postnatal day 21)
- Organ weights: heart, lungs, spleen, liver, and kidneys
- Haematology: haematocrit, haemoglobin
- Clinical chemistry: GOT, GPT, bilirubin, total protein, urea, uric acid, glucose, cholesterol, and creatinine

Statistics:

The significance of the differences in the results was determined by the t-Studens-Fischer test. A difference is considered significant when P <= 0.05.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no data

Details on maternal toxic effects:
no data

Effect levels (maternal animals)

1

Dose descriptor:

LOEL

Effect level:

12 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

2

Dose descriptor:

LOEL

Effect level:

22.9 mg/kg bw/day (actual dose received)

Based on:

other: CoC6H6O7

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
- The number of litters was decreased
- Ratio living/dead was decreased; significant decrease in living young/litter at 48 mg/kg bw at day 4 and 21.
- Average body weight by litter was decreased (dose-dependent)

Body weight (to 59% and 69% of the control value in males and females, respectively), body length (to 83% and 82% of the control value in males and females, respectively) and tail length (to 78% and 77% of the control value in males and females, respectively) in all dose groups were significantly decreased in males and females compared to control (dose-dependent).
No external malformations were observed in any case.

Organ weights: In males, the relative liver weight were decreased in the low and high dose groups compared to control. The weights of lungs and kidneys were only decreased in the low dose group.
In females, the relative liver and spleen weights were significantly decreased in all dose groups.
As no dose-dependency was detected, the effects cannot be clearly considered treatment-related.

Haematology/Clinical chemistry: All paramters examined were within the normal range.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Based on the result of this study it was concluded that cobalt administration to pregnant rats from gestation day 14 until day 21 of lactation, produces toxic effects on the mothers, which have a repercussion on the late gestation. A delay in growth on the living young is observed. However, no signs of general toxicity were seen in the offspring.