Lime (chemical), hydraulic

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well-documented publication. When administered via the oral route, lime (chemical) hydraulic, namely the main constituent calcium hydroxide, will be neutralised in the GI tract. Other main constituents or major impurities (calcium carbonate, calcium silicate, calcined clay minerals) are not identified as hazardous substances and therefore considered not to be of toxicological concern. Therefore, calcium will remain as the only substance of potential toxicological relevance. Under physiological conditions the hydroxyl-ions released from the test substance calcium oxide are neutralised e.g. in the GI tract and are therefore not relevant for consideration of systemic toxicity. Therefore the objective of the study was the evaluation of any effects of calcium. In view of the limited relevance of the anionic counter-ions discussed here, calcium released both from calcium oxide and lime (chemical) hydraulic can be considered as equivalent, and the results of the study can be used by read-across. The study allows the derivation of a NOAEL value for effects of Ca regarding developmental toxicity in rats and mice.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Calcium oxide

EC Number:

215-138-9

EC Name:

Calcium oxide

Cas Number:

1305-78-8

Molecular formula:

CaO

IUPAC Name:

Calcium oxide

Details on test material:

- Name of test material (as cited in study report): FDA 73-41 (calcium oxide)
- Physical state: solid
No further details are given.

Test animals

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: Mice were housed in groups in disposable plastic cages.
- Diet: ad libitum
- Water: ad libitum; tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-27
- Humidity (%): 64-78

No further details are given.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

no detailed data given

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no detailed data given

Details on mating procedure:

The female mice were mated with young adult males.
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1; one male was not permitted to impregnate more than one female per group.
- Length of cohabitation: no data
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
No further details are given.

Duration of treatment / exposure:

Day 6 to 15 of gestation.

Frequency of treatment:

Once daily.

Duration of test:

Until day 17 of pregnancy.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
4.4 mg/kg
Basis:
nominal in water

Doses / concentrations 2

Remarks:

Doses / Concentrations:
20.4 mg/kg
Basis:
nominal in water

Doses / concentrations 3

Remarks:

Doses / Concentrations:
94.8 mg/kg
Basis:
nominal in water

Doses / concentrations 4

Remarks:

Doses / Concentrations:
440 mg/kg
Basis:
nominal in water

No. of animals per sex per dose:

mated: 25 to 26 mice
pregnant: 17 to 21 mice

Control animals:

yes

yes, sham-exposed

Details on study design:

no data available

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All animals were observed daily for appearance and behaviour.

BODY WEIGHT: Yes
- Time schedule for examinations: Average body weight was determined on days 0, 6, 11, 15 and 17

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes; however, compound intake occurred by gavage.
- Time schedule: All animals were observed daily with particular attention to food consumption and weight.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data; not applicable

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 17
- Organs examined: The urogential tract of each dam was examined in detail for anatomical normality.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: Yes

Statistics:

no data given

Indices:

no data given

Historical control data:

no data given

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Administration of up to 440 mg/kg bw/d of CaO to pregnant mice for 10 consecutive days had no clearly discernible effect on maternal survival.

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

>= 440 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

2

Dose descriptor:

NOAEL

Effect level:

>= 315 mg/kg bw/day

Based on:

element

Remarks:

Ca

Basis for effect level:

other: developmental toxicity

3

Dose descriptor:

NOAEL

Effect level:

>= 440 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

4

Dose descriptor:

NOAEL

Effect level:

>= 315 mg/kg bw/day

Based on:

element

Remarks:

Ca

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Administration of up to 440 mg/kg bw/d of CaO (= 315 mg Ca/kg bw/d) to pregnant mice for 10 consecutive days had no clearly discernible effect on foetal survival.
The number of abnormalities seen in either soft or skeletal tissues of test groups did not differ from the number occuring spontaneously in sham-treated controls.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Administration of up to 440 mg/kg bw/d of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of test groups did not differ from the number occuring spontaneously in sham-treated controls.