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EC number: 233-296-7 | CAS number: 10108-64-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
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- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
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- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
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- Endpoint summary
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- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on generations indicated in Effect levels (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no information
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: reliable with restrictions. Well documented publication, but some details are missing. Useful for evaluation.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Toxicity, fertility, teratogenicity, and dominant lethal tests in rats administered cadmium subchronically II. Fertility, Teratogenicity, and Dominant Lethal Tests
- Author:
- Sutou S, Yamamoto K, Sendota H and Sugiyama M
- Year:
- 1 980
- Bibliographic source:
- Ecotox. Environ. Saf. 4:51-56
Materials and methods
- Principles of method if other than guideline:
- Method:
Males and females within each treatment group (+ control) were mated 6 d/wk for 3 wk changing partners every week if needed. Cd was
administered during the mating period. Copulation was confirmed by detection of spermatozoa in vaginal smears. Pregnant F were administered
Cd during gestation and killed on Day 20 of gestation for developmental test (fetal examination). Nonpregnant females were killed after a total
administration period of 13 wk.
Additionally: After a total of 9 wk of administration, males were mated with 2 virgin females per male per week for 6 wk. Pregnant F were killed on
Day 13 of gestation for dominant lethal tests (examination of the numbers of corpora lutea, live fetuses, early deaths (no remnants of fetuses), and
late deaths (remnants of fetuses)). One week after the cessation of dominant lethal tests, which represents a recovery period of 50 d, male rats
were killed and examined. - GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Cadmium chloride
- EC Number:
- 233-296-7
- EC Name:
- Cadmium chloride
- Cas Number:
- 10108-64-2
- Molecular formula:
- CdCl2
- IUPAC Name:
- cadmium(2+) dichloride
- Details on test material:
- -Name of test material-CdCl2,
-Source-Wako Pure Chemical Industries, Ltd
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Origin/housing: purchased at age of 4 wk from Shizuoka Agricultural Cooperative Association for Laboratory Animals.
The animals were freely supplied with pelleted dry chow (NMF, Oriental Yeast Co.) and water and kept in wire cages in pairs. The cages were placed in a fully air-conditioned facility where the temperature was regulated at 24 ± 1°C, and the humidity at 55 ± 5%. After a taming period of a week, the test
was started.
- Age at start of study: 5 wk
- Weight at study initiation: no data
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on exposure:
- no information
- Details on mating procedure:
- Method:
Males and females within each treatment group (+ control) were mated 6 d/wk for 3 wk changing partners every week if needed. Cd was
administered during the mating period. Copulation was confirmed by detection of spermatozoa in vaginal smears. Pregnant females were administered Cd during gestation and killed on Day 20 of gestation for developmental test (fetal examination). Nonpregnant females were killed after a total
administration period of 13 wk.
Additionally: After a total of 9 wk of administration, males were mated with 2 virgin females per male per week for 6 wk. Pregnant F were killed on
Day 13 of gestation for dominant lethal tests (examination of the numbers of corpora lutea, live fetuses, early deaths (no remnants of fetuses), and
late deaths (remnants of fetuses)). One week after the cessation of dominant lethal tests, which represents a recovery period of 50 d, male rats
were killed and examined. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no information
- Duration of treatment / exposure:
- Exposure period: 6 wk prior to mating + 3 wk mating period
Premating exposure period (males): 6 wk
Premating exposure period (females): 6 wk - Frequency of treatment:
- Once daily for 9 wk
- Details on study schedule:
- See test method under 'Details on mating procedure'
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 0.1, 1.0 and 10.0 mg Cd/kg bw/d
Basis:
no data
- No. of animals per sex per dose:
- 14 males and 14 females per treatment group (and control)
- Control animals:
- yes
- Details on study design:
- no information
- Positive control:
- none
Examinations
- Parental animals: Observations and examinations:
- reproducitve performance
- Oestrous cyclicity (parental animals):
- no information
- Sperm parameters (parental animals):
- no information
- Litter observations:
- presence of gross anomalies and viability
- Postmortem examinations (parental animals):
- no information
- Postmortem examinations (offspring):
- skeletal anomalies
- Statistics:
- t-test: to determine the significance of differences between average numbers of corpora lutea, total implantations, and live fetuses per female,
average fetal body weight and placental weight per litter, and average length of fetal body and fetal tail per litter for each treatment, compared with thecontrol values. Preimplantation losses were determined by subtracting the number of total implantations from the number of corpora lutea. The
preimplantation losses, early deaths, late deaths, and total death for each female were transformed to the Freeman-Tukey arc sine form, and then
subjected to the t-test to compare values for each treatment with the control value. Fertility indices analyzed were as followes: copulating ability
(copulating males/total males), impregnating ability (impregnating males/total males), copulated ratio (copulated females/total females), pregnant
ratio (pregnant F/total F), and pregnancy efficiency (pregnant F/copulated F).
X2 test: for fertility indices to compare the values of each treatment group with the control value. It was tested whether the fertility indices were
linearly related to arithmetic or logarithmic dose. The proportion of F with one or more dead implantations in each treatment group was compared
with the control value in the same way as for the fertility indices, by X2 and Armitage’s X2 tests.
Regression analysis: to determine whether the average number of implantations per F was related to the arithmetic or logarithmic dose.
The rank sum test: to compare the number of resorbed fetuses per F and the average number of skeletal variations per litter for each treatment
group with the control value. An analysis of variance across 6 weeks was made for the average number of total implantations per F, preimplantation
losses per F (using the Freeman-Tukey arc sine transformation), total deaths per F (using the arc sine transformation), and the ratio of deaths to the total implantations per F (using the arc sine transformation) - Reproductive indices:
- copulating ability and impregnating ability of males and copulated ratio, pregnant ratio, and pregnancy efficiency of females
- Offspring viability indices:
- no information
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not examined
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- effects observed, treatment-related
Details on results (P0)
Parental data: The numbers of copulating and pregnant females decreased at 10 mg Cd/kg bw/d. Consequently, the average numbers of total implantations and live fetuses per female decreased, and the average number of resorbed fetuses increased significantly at the highest dose (10 mg/kg bw/d). The higher the dose levels, the smaller the average number of total implantations and live fetuses, although the differences from the control were not significant in the two lower dose groups (0.1 and 1.0 mg/kg bw/d). For details see table 1 under remarks on results.
In dominant lethal tests, five fertility indices (copulating ability and impregnating ability of males and copulated ratio, pregnant ratio, and pregnant efficiency of females) were statistically analyzed for significant differences from the control values. No difference was observed, indicating that the administration of Cd at oral dose levels of less than 10 mg/kg bw/d for 9 wk did not affect fertility of male rats.
The number of impregnated F1 and the average numbers of corpora lutea, total implantations, preimplantation losses, live fetuses, late deaths, and total deaths per F did not show any significant differences from the control values. The analysis of variance across 6 wk for total implantations, preimplantation losses, total deaths, and the ratio of deaths to the total implantations also showed no differences compared with the control values. The proportions of F with one or more dead implantations in all treatment groups were similar to each other.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 1 mg/kg bw/day
- Sex:
- female
- Dose descriptor:
- NOAEL
- Remarks:
- reproductive
- Effect level:
- 1 mg/kg bw/day
- Sex:
- female
- Dose descriptor:
- LOAEL
- Remarks:
- reproductive
- Effect level:
- 10 mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: >50% fewer copulating and pregnant females
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings:
- not specified
Details on results (F1)
Gross anomalies-
Body weight, body length, and tail length of fetuses from the highest dose showed significant decreases in both males and females, compared to the control values. These fetuses were small and yellowish in color, indicative of anemia and malnutrition. The average weight of the placentas increased significantly in the highest dose. Even in the two lower dose groups placental weight was greater than the control value in both M and F (supposed to be adaptative hypertrophy).
Visceral anomalies-
No marked changes were detected. Hydronephrosis was observed in one rat in each group. Since the number of fetuses examined in the highest dose group was small, the percentage of this anomaly was high, but no definite conclusion can be drawn form these data.
Skeletal anomalies-
As mentioned in table 1, the fetuses from the highest dose group were small and showed growth retardation which was reflected in delayed ossification of the sternebrae and the small number of ossified caudal vertebrae.
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- ca. 1 mg/kg bw/day
- Sex:
- male/female
- Dose descriptor:
- LOAEL
- Generation:
- F1
- Effect level:
- 10 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: delayed ossification, decreased body weight
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
Parental data: see repeat dose tox test
- Table 1: Fertility
Dose (mg/kg/ d) |
n° of animals |
copulating |
Pregnant |
corpora lutea1 |
total implants1 |
live fetuses1 |
macerated |
resorbed |
0 |
14 |
14 |
11 |
15.2 (2.0) |
14.7 (2.0) |
14.2 (2.0) |
0 |
0.55 |
0.1 |
13 |
13 |
10 |
14.2 (2.0) |
13.9 (1.7) |
13.9 (1.7) |
0 |
0.70 |
1.0 |
13 |
12 |
12 |
15.5 (1.8) |
13.6 (1.8) |
13.1 (2.3) |
0 |
0.50 |
10.0 |
13 |
5 |
5 |
13.6 (1.5) |
10.6 (3.1)** |
7.2 (2.4) |
0.8 |
2.6* |
|
|
|
|
|
|
|
|
|
1Mean and (standard deviation)
* significantly different from the control at P < 0.05
**: significantly different from the control at P < 0.01
- Data on fetuses: gross anomalies:
Table 2: Male fetuses
dose (mg Cd/kg/d) |
0 |
0.1 |
1.0 |
10.0 |
N° of fetuses |
71 |
73 |
73 |
15 |
Body weight (g) |
3.63 (0.10) |
3.58 (0.23) |
3.52 (0.27) |
2.41 (0.29)** |
Body length (mm) |
39.1 (0.4) |
39.2 (0.9) |
93.0 (1.1) |
35.2 (1.0)** |
Tail length (mm) |
13.8 (0.3) |
13.7 (0.3) |
14.0 (0.5) |
12.3 (1.1)* |
Placenta (mg) |
502 (25) |
524 (60) |
530 (49) |
548 (46)* |
Table 3: Female fetuses
dose (mg Cd/kg/d) |
0 |
0.1 |
1.0 |
10.0 |
N° of fetuses |
85 |
59 |
84 |
21 |
Body weight (g) |
3.48 (0.16) |
3.40 (0.25) |
3.37 (0.23) |
2.32 (0.23)** |
Body length (mm) |
38.5 (0.5) |
39.4 (3.4) |
38.2 (0.8) |
34.3 (1.2)** |
Tail length (mm) |
14.1 (0.3) |
14.0 (0.5) |
14.3 (0.3) |
12.5 (0.9)* |
Placenta (mg) |
479 (30) |
501 (78) |
500 (57) |
554 (73)* |
Figures are given as mean and (standard deviation)
* significantly different from the control at p < 0.05
** significantly different from the control at p < 0.01
Table 4: Data on fetuses: visceral anomalies
dose (mg Cd/kg/d) |
0 |
0.1 |
1.0 |
10.0 |
N° of fetuses |
53 |
44 |
54 |
12 |
Hemorrhage in facial area (%) |
3 (5.7) |
0 |
4 (7.5) |
0 |
Hemorrhage in adrenal (%) |
3 (5.7) |
1 (2.2) |
0 |
0 |
Hemorrhage in abdominal cavity (%) |
1 (1.9) |
2 (4.5) |
0 |
0 |
Dilatation of renal pelvis (%) |
7 (13.2) |
9 (20.0) |
7 (13.0) |
1 (8.3) |
hydronephrosis |
1 (1.9) |
1 (2.2) |
1 (1.9) |
1 (8.3) |
Table 5: Data on fetuses: skeletal anomalies
dose (mg Cd/kg/d) |
0 |
0.1 |
1.0 |
10.0 |
N° of fetuses |
103 |
88 |
104 |
24 |
Delayed ossificationof: |
|
|
|
|
Os parietale (%) |
0 |
6 (6.8) |
0 |
0 |
Os interparietale (%) |
3 (2.9) |
13 (14.8) |
3 (2.8) |
2 (8.3) |
Os sphenoides (%) |
5 (4.9) |
12 (13.6) |
2 (1.9) |
4 (16.7) |
Cervical vertebrae (%) |
0 |
0 |
0 |
2 (8.3) |
Sternebrae |
|
|
|
|
1st(%) |
0 |
1 (1.1) |
0 |
2 (8.3) |
2nd(%) |
0 |
1 (1.1) |
2 (1.9) |
6 (25.0) |
3rd(%) |
0 |
1 (1.1) |
4 (3.8) |
0 |
4th(%) |
1 (1.0) |
3 (3.4) |
5 (4.8) |
7 (28.0) |
5th(%) |
33 (32.0) |
37 (42.0) |
38 (36.5) |
21 (87.5)** |
6th(%) |
26 (25.2) |
28 (31.8) |
22 (21.2) |
24 (100)** |
Cervical rib(%) |
0 |
0 |
0 |
3 (12.5) |
14thrib(%) |
11 (107) |
14 (15.9) |
1 (1.0) |
0 |
N° of caudal vertebrae |
4.21+/- 0.40 |
3.87+/- 0.33 |
4.09+/-0.47 |
2.13+/-1.18** |
* significantly different from the control at P < 0.05
** significantly different from the control at P < 0.01
Applicant's summary and conclusion
- Conclusions:
- Rats at the dose of 10 mg/kg bw/d exhibited toxic signs. These rats showed reduced fertility but neither teratogenicity nor dominant lethality was observed. As both sexes were treated it was not clear from the fertility studies which sex was more affected. However the negative outcome of dominant lethal tests (treated M and untreated F) suggested that females were more strongly affected than males.
According to the authors, the effects seen in the fertility studies can perhaps be explained mainly in terms of two factors: anemia and hormonal
imbalance. This study with acceptable test design and study reporting appears to be the most critical study related to effects on fertility. - Executive summary:
A study was conducted to evaluate the effects of the test material on the reproductive performance of parental rats and fetal development.
Males and females within each treatment group were mated 6 d/wk for 3 wk and the test material was administered at 0, 0.1, 1.0 and 10.0 mg Cd/kg bw/d during the mating period. Pregnant females were administered Cd during gestation and killed on Day 20 of gestation for developmental test (fetal examination). Nonpregnant females were killed after a total administration period of 13 wk. Additionally after a total of 9 wk of administration, males were mated with 2 virgin females per male per week for 6 wk. Pregnant females were killed on Day 13 of gestation for dominant lethal tests (examination of the numbers of corpora lutea, live fetuses, early deaths (no remnants of fetuses), and late deaths (remnants of fetuses)). One week after the cessation of dominant lethal tests, which represents a recovery period of 50 d, male rats were killed and examined.
A dose of 10 mg/kg bw/d (as CdCl2) for 9 wk did not affect the fertility of male rats in dominant lethal tests. The five analysed fertility indices (copulating ability and impregnating ability of males and copulated ratio, pregnant ratio, and pregnancy efficiency of females) did not reveal a difference with control rats when males were mated with untreated females. When treated males were mated with females having undergone the same Cd treatment, adverse effects were observed in the 10 mg/kg/day group on number of copulation and pregnancies, on the number of implants and live fetuses (NOAEL: 1 mg Cd/kg bw/d).
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