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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 based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to OECD guideline study used for read-across purposes

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Method: other
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
Calcium chloride
EC Number:
233-140-8
EC Name:
Calcium chloride
Cas Number:
10043-52-4
IUPAC Name:
calcium dichloride
Details on test material:
Test substance: Fine white granular material marked with FDA 71-87.

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
6th to 15th day of pregnancy
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
1.76, 8.18, 38.0, 176 mg/kg/day
Basis:

Control animals:
other: sham-treated
Details on study design:
Sex: female
Duration of test: up to the last day of pregnancy

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
> 176 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
> 176 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

- Table 1: Fate Summary
-------------------------------------------------------
Group Material Dose*** Total Surviving at
Term
---------------------------
mg/kg Mated Pregnant Total Pregnant*
--------------------------------------------------------
341 Sham 0.0 25 25 25 25
342 Aspirin** 250.0 25 23 25 23
347 CaCl2 1.76 25 22 25 22
348 CaCl2 8.18 25 24 25 24
349 CaCl2 38.0 25 22 25 22
350 CaCl2 176.0 25 24 24 23
--------------------------------------------------------
* Includes all dams examined at term
** Positive Control: 250.0 mg/kg
*** Administered as a water solution
- Table 2: Reproduction Data
--------------------------------------------------------
Group 341 342 347 348 349 350
Dose (mg/kg) sham Aspirin* 1.76 8.18 38.0 176.0
--------------------------------------------------------
-----Pregnancies-----
Total No. 25 23 22 24 22 24
Died or Aborted
(before Day 20) 0 0 0 0 0 1
To term (on Day 20) 25 23 22 24 22 23
-----Live Litters-----
Total No.** 25 18 22 24 22 23
-----Implant Sites-----
Total No. 279 231 234 261 254 246
Average/dam** 11.2 10.0 10.6 10.9 11.6 10.7
-----Resorptions-----
Total No.** 4 62 3 1 1 2
Dams with 1 or more
sites resorbed 3 1 2 1 1 2
Dams with all
sites resorbed - 4 - - - -
% partial resorptions
12.0 47.8 9.09 4.17 4.55 8.70
% complete resorptions
- 17.4 - - - -
-----Live Fetuses-----
Total No. 275 168 231 260 253 244
Average/dam** 11.0 7.30 10.5 10.8 11.5 10.6
Sex ratio (M/F) 1.07 1.06 1.10 0.95 0.90 0.89
-----Dead Fetuses-----
Total** - 1 - - - -
Dams with 1 or
more dead - 1 - - - -
Dams with all dead - 1 - - - -
% partial dead - 4.35 - - - -
% all dead - 4.35 - - - -
-----Average Fetus Weight (g)-----
3.68 2.39 4.13 3.80 3.84 3.72
----------------------------------------------------------
* Positive Control: Aspirin 250.0 mg/kg
** Includes only those dams examined at term.

- Table 3: Summary of Skeletal Findings**
---------------------------------------------------------
Group No. 341 342 347 348 349 350
Dose (mg/kg) Sham Aspirin* 1.76 8.18 38.0 176.0
---------------------------------------------------------
Live Fetuses Examined
(at term)
191/25 120/18 161/22 180/2 176/22 173/23
-----Sternebrae-----
Incomplete oss.
86/22 44/15 34/13 53/14 51/16 47/17
Scrambled
Bipartite 1/1 2/2 - 1/1 - 1/1
Fused
Extra
Missing 34/17 103/18 15/9 19/10 18/9 12/7
Other
-----Rids-----
Incomplete oss.
- 15/9 1/1 3/2 - 1/1
Fused/split
Wavy 22/10 41/16 13/9 11/6 34/17 19/10
Less than 12 - 1/1 - 3/1 - -
More than 13 - 95/17 - 4/3 1/1 2/2
Other
-----Vertebrae-----
Incomplete oss.
24/14 76/18 23/10 12/7 34/13 20/9
Scrambled
Fused
Extra ctrs. oss.
Scoliosis - 1/1 - - - -
Tail defects
Other; spina bifida
- 1/1 - - - -
-----Skull-----
Incomplete closure
36/13 54/17 25/11 54/19 40/17 31/13

Missing - 2/2 - - - -
Craniostosis
Other
-----Extremities-----
Incomplete oss. - 3/3 - - - -
Missing
Extra
-----Miscellaneous-----
Hyoid;
missing 26/14 57/17 14/9 9/7 25/9 15/9
Hyoid;
reduced 17/12 8/4 18/7 33/17 23/12 16/10
----------------------------------------------------------
* Positive Control: 250.0 mg/kg
** Numerator = Number of fetuses affected;
Denominator = Numbre of litters affected.
- Table 4: Summary of Soft Tissue Abnormalities
---------------------------------------------------------
Group Material Dose Level Dam Number Description
(mg/kg) of Pups
---------------------------------------------------------
342 Aspirin* 250.0 A7088 1 Meningoencephalocele
A7093 3 Encephalomyelocele;
umbilical hernia
1 Hydrocephalus;
exophthalmos;
gastroschisis
A7107 1 Meningoencephalocele;
umbilical hernia
347 CaCl2 1.76 N6016 1 Gastroschisis
---------------------------------------------------------
* Positive Control: 250.0 mg/kg

- Table 5: Average Body Weights*** (g)
---------------------------------------------------------
Group Material Dose Day0 Day6 Day11 Day15 Day20**
Level
(mg/kg)
---------------------------------------------------------
341 Sham 0.0 232 252 268 295 353
(25)
342 Aspirin* 250.0 226 247 253 268 311
(23)
347 CaCl2 1.76 229 248 265 286 353
(22)
348 CaCl2 8.18 226 246 261 279 345
(24)
349 CaCl2 38.0 226 247 264 285 357
(22)
350 CaCl2 176.0 231 251 262 280 346
(23)
---------------------------------------------------------
* Positive Control: 250.0 mg/kg
** Number of surviving dams in parentheses (c.f. Table 1)
*** Of pregnant dams


Applicant's summary and conclusion

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