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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:
supporting study
Study period:
1971
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Minimally-documented study of effects on foetal development after strontium exposure. Experimental information in the publication is limited. Number of animals is low (n=3), although 4 concentrations were included. No information on presence of maternal toxicity. Rats were only exposed during day 9-19 of pregnancy. Study performed with the substance analogue Strontium dinitrate. The rationale for the analogue approach is attached in section 13.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1971

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no
Remarks:
Study performed before GLP principles were in place.
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: no data
- Diet: standard diet (0.9% calcium, negligible quantities of strontium)
- Water: ad libitum, distilled water

ENVIRONMENTAL CONDITIONS
- No data

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
water
Details on exposure:
No further data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Details on mating procedure:
Virgin female rats were mated with proven males.
Duration of treatment / exposure:
Days 9 to 19 of pregnancy
Frequency of treatment:
daily
Duration of test:
Female rats were killed at day 19 of pregnancy.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 25, 50, 100, 200 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
3
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
No data.
Ovaries and uterine content:
- Number of foetuses recorded
- Number of resorptions recorded
Fetal examinations:
- External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- 3 foetuses from mothers given 50 and 200 mg/kg bw/day were ashed and analysed for their calcium and strontium content.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no data

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Dose descriptor:
NOAEL
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
- Progeny from treated mothers did not differ from the controls in size or body weight.
- Litter sizes and the number of resorption sites were similar to those of the control group.
- Skeletons of exposed foetuses were normal and the zones of calcification in the bones were of normal proportions.
- No histological changes were detected in the soft tissues and the skeletal tissues exhibited the characteristic degree of ossification for 19-day-old rats foetuses.
- Histochemical staining of strontium was observed in ossifying regions and not in soft tissues.
- No difference detected in Sr content of foetuses from rats exposed to 50 or 200 mg/ kg bw/day (approx. 5.4 ppm and 4.6 ppm; no unexposed foetuses included). Calcium content decreased with increased dosing of maternal animal (approx. 215 ppm and 82 ppm for foetuses from rats exposed to 50 or 200 mg/ kg bw/day resp.). It was not investigated which effect this had on pup development, the effect of Sr on developmental toxicity is inconclusive.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
>= 200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Based on the absence of effects on foetuses after exposure of the mothers to 0, 25, 50, 100 or 200 mg strontium dinitrate/ kg bw/ day from days 9 to 19 of pregnancy (subcutaneously), a NOAEL for teratogenicity was established at 200 mg/kg bw/day.
Executive summary:

Female rats were exposed subcutaneously to 0, 25, 50, 100 or 200 mg strontium dinitrate/ kg bw/ day from days 9 to 19 of pregnancy. No data are given on maternal toxicity. After sacrifice, the foetuses were analysed histologically. Total numbers of foetuses and resorption sites were not altered after exposure. The progeny from treated mothers did not differ from the controls in size or body weight. Skeletons of exposed foetuses were normal and the zones of calcification in the bones were of normal proportions. No histological changes were detected in the soft tissues and the skeletal tissues exhibited the characteristic degree of ossification for 19-day-old rats foetuses. Strontium was detected in ossifying regions and not in soft tissues of exposed foetuses. A substance-related decrease of Ca was detected at 200 mg/kg bw/day, however this finding did not coincide with soft tissue or skeletal effects. Based on these data, a NOAEL for teratogenicity was established at 200 mg/kg bw/day. According to the rationale attached in section 13, the observations can be read-across to Strontium hydrogenphosphate. However, since it was not investigated which effect the decreased Ca levels had on pup development, the effect of Sr on developmental toxicity is inconclusive.