Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

In a OECD guideline combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (NIER 2002), calcium sulfate, dihydrate was administered by gavage at the dose levels of 0, 100, 300 and 1,000 mg/kg bw/day for more than 35 days and 41~45 days for male and female rats respectively and the pre-mating exposure period was 14 days. No adverse effects were observed in terms of fertility, delivery and nursing in parent animals during the test period. There were no signs of reproduction/developmental toxicity on the body weight gestation index, sex ratio, clinical signs or viability up to 1,000 mg/kg/day (highest dose tested). According to the result of reproductive toxicity screening test, the NOAEL for calcium sulfate dihydrate was the highest dose tested (1000 mg/kg day) which equates to 790 mg/kg bw day for calcium sulfate anhydrous.

Calcium sulfate dihydrate showed no signs of reproduction/developmental toxicity in an OECD 422 reproduction/developmental screening test.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to GLP and guideline
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: 254.2 - 297.8 g (males) and 182.7 - 208.2 g (females)
Route of administration:
oral: gavage
Details on mating procedure:
- M/F ratio per cage: 1:1 (from same test group)
- Length of cohabitation: 4 days
- Proof of pregnancy:sperm in vaginal smear
Duration of treatment / exposure:
Premating exposure period of 2 weeks
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
No. of animals per sex per dose:
60
Control animals:
yes, concurrent no treatment
Details on study design:
A pre-treatment test was conducted with 0, 125, 250, 500 and 1,000 mg/kg/day of test substance for 7 days to determine the appropriate starting dose level.

Parental animals: Observations and examinations:
Clinical observations performed and frequency: Clinical symptoms were observed once a day but were observed once a week in detail; a death rate was observed twice a day; and body weight was observed once a week and just before the necropsy, but in case of pregnant females, it was measured on the day 0, 7, 14, 20 of gestation period, date of delivery, and 4 days after the delivery; consumption rate of fodder was observed once a week except mating period.







Litter observations:
Observation of F1:
The number of survivors and deaths during delivery
Body weight and Survival rate: measured on the day 0 and 4 after the delivery
Postmortem examinations (parental animals):
A number of implantation and corpus luteum: while female animals were necropsied, the number of corpus leteum and implantation were
counted; and the former was measured in the ovary and the latter was measured in the uterus.

Organ weight: testes, epididymider (all males) liver, kidney, adrenals, thymus, spleen, brain, and heart (5 male and female animals from each test group).

- Fixation: 22 kinds of tissues were fixed to do histopathologic tests such as testes, epididymides, ovaries, accessory sex organs for all animals, brain (including cerebrum, cerebellum and pons), spinal cord, stomach, small and large intestines (including peyer’s patches), liver, kidneys, adrenals, spleen, heart, thymus, thyroid, trachea, lungs, uterus, urinary bladder, lymph nodes (cervical mesenteric), peripheral nerve (sciatic or tibial), bone marrow.






Statistics:
Statistical decision tree, but in case of recovery group, either two-side Students t-test or two-side Apsin Welch t-test was used. In case of categorical data, two-sided Fishers exact test was used.
Pregnancy and delivery: There was no significant difference between the treatment groups and the control group in terms of delivery and; the number of corpus luteum and implantation. Some animals in the test groups including the control group had quite higher loss rate of the embryo prior to the implantation and the fetus after the implantation but significant difference was not observed between the treatment group and the control group. These higher loss rate were occurred spontaneously and no dose-response correlation, thus no influence under test substance.


Index of copulation, fertility and gestation: Every test group including control group was succeeded in the mating, but each animal from every group was not succeeded in the gestation. However, all pregnant female animals were succeeded in the delivery. Therefore, no significant difference between the treatment group and the control group was found.

- Clinical signs: In male control group, a case of salivation and bloodylike secretion was observed on the day 11 and 12. In the 1,000 mg/kg/day treatment group, a case of depilation, dcab and pus was observed on the left cheek between the day 25 and the closing day. However, the frequency of occurrence was low and no dose-response correlation. Thus these symptoms were not influenced by test substance. In female control group, a case of genitalia bloody-like secretion was observed at day 29. In the 100 mg/kg/day treatment group, each case of hypoactivity and depilation was observed on the day 8 and 9, and between day 44 and the closing day, respectively. However, these symptoms were disappeared in short, thus these symptoms did not have relationship with test substance.


Necropsy opinions: For male animals, in the control group within the recovery group, a case of left and right caput epididymis cyst was observed and the 1,000 mg/kg/day recovery group had symptom of right caput epididymis cyst. However, its frequency of occurrence was low and it was even observed at the control group within the recovery group, so it did not have relationship with test substance. For female animals, in the 300 mg/kg/day treatment group, each animal was dead on the day 7 and 14 and; each case of lung dark-red discolouration was observed, but white particles in a lobe of the lung was observed just from one of carcasses. A case of spleen white nodule was observed for an animal in the 300 mg/kg/day treatment group. There was a case of right adrenal gland white spots at the 1,000 mg/kg/day treatment group. In the control group within the recovery group, each case of right adrenal gland hemorrhagia and atrophy and liver adhesion with diaphragm was observed. However, their frequencies of occurrence were low and no dose-response correlation, so these did not have relationship with test substance.













Dose descriptor:
NOAEL
Remarks:
reproductive toxicity
Effect level:
790 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: The result has been corrected to calcium sulfate anhydrous
Critical effects observed:
no
Number of pups born, viability and sex ratio: No significant difference was observed between the treatment group and the control group at the time of the delivery and on the day 4 after the delivery. There were reconfirmed of sex ratio at the day 7 after the delivery since total 8 cases of sex were decided again. For instance, each 2 cases of misconfirmation of sex was found at the following three treatment groups such as 100, 300, 1,000 mg/kg/day as their sexes were replaced from male to female; and each case of mis-confirmation of sex was found at the 300 mg/kg/day and 1,000 mg/kg/day, for their sexes were replaced to male.(refer to table 1 for results)


Dose descriptor:
NOAEL
Generation:
F1
Effect level:
790 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: The result has been corrected for calcium sulfate anhydrous
Critical effects observed:
no
Reproductive effects observed:
no

Table 1:

DOSE: (mg/kg)

0

100

300

1000

No. of mated males

Copulation index (%)

Fertility index (%)

No. of mated females

Copulation index (%)

Fertility index (%)

Gestation index (%)

No. of corpora lutea

Mean ± S.D

No. of implantations

Mean ± S.D

Mean % preimplantation loss

No. of embryo/fetal death

No. of live pups born

Mean ± S.D

Mean pregnancy period (day)

Viability index on day at birth(%)

Viability index on day 4 pp (%)

Body weights of pups (g)

Male (at birth)

4 DAY

Female (at birth)

4 DAY

12

100.0

91.7

12

100.0

91.7

100.0

17.2

2.6

15.1

2.5

11.6

1.5

13.5

2.2

21.8

99.0

98.0

 

6.49

9.78

6.19

9.44

12

100.0

91.7

12

100.0

91.7

100.0

17.0

3.4

13.6

4.1

20.2

1.0

12.6

4.0

21.7

99.4

98.3

 

6.42

9.86

6.06

9.13

10

100.0

90.0

10

100.0

90.0

100.0

17.4

3.5

15.7

1.9

9.0

0.7

15.0

1.8

22.0

98.0

97.8

 

6.56

9.70

6.23

9.37

12

100.0

91.7

12

100.0

91.7

100.0

17.2

1.9

15.4

4.3

10.3

0.7

14.6

4.5

22.0

100.0

97.6

 

6.55

9.52

6.26

8.74

Conclusions:
According to the results of the reproductive toxicity test the NOAEL was the highest dose tests (1000 mg/kg) which was corrected to 790 mg/kg for calcium sulfate anhydrous. Calcium sulfate was not considered to be toxic to reproduction or development
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
790 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

In a guideline equivalent teratology study (Morgareidge 1974) mice, rats and rabbits were dosed by oral gavage with calcium sulfate up to 1600 mg/kg. Body weights of live pups were recorded and all foetuses were examined for the presence of external congenital abnormalities. One third of the foetuses for each litter underwent detailed visceral examinations.

Administration of up to 1600 mg/kg bw of calcium sulfate to pregnant mice for 10 consecutive days had no clearly discernable effects on nidation or on maternal or foetal survival.

Administration of up to 1600 mg/kg bw of calcium sulfate to pregnant rats for 10 consecutive days had no clearly discernable effects on nidation or on maternal or foetal survival.

Rabbits: up to 1600 mg/kg bw of calcium sulfate to pregnant rabbits for 13 consecutive days had no clearly discernable effects on nidation or on maternal or foetal survival.

Calcium sulfate had no effects on nidation or on maternal or foetal survival in mice,rats and rabbits at doses up to 1600 mg/kg bw.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is well documented and comparabale to a guideline but not performed to GLP
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Remarks:
Predates GLP
Limit test:
no
Species:
other: mice, rats and rabbits
Strain:
other: Albino CD-1 outbred mice; Wistar derived albino rats; Dutch-belted rabbits
Details on test animals and environmental conditions:
Mice:
Adult virgin mice were gang-housed in disposable plastic cages in temperature and humidty controlled quarters with free access to food and fresh tap water.

Rats:
Adult virgin rats were individually housed in mesh bottom cages in temperature and humidity-controlled quarters with free access to food and fresh tap water.

Rabbits:
Adult virgin rabbits were individually housed in mesh bottom cages in temperature and humidity-controlled quarters with free access to food and fresh tap water.
Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
Mice: beginning on Day 6 and continuing daily through Day 15 of gestation the females were dosed with the indicated doses.

Rats: beginning on Day 6 and continuing daily through Day 15 of gestation the females were dosed with the indicated doses.

Rabbits: beginning on Day 6 and continuing daily through Day 18 the females were dosed.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
None specified
Details on mating procedure:
Mice: mated with young adult males, and observation of the vaginal sperm plug was considered Day 0 of gestation.

Rats: mated with young adult males, and observation of the vaginal sperm plug was considered Day 0 of gestation.

Rabbits: On Day 0, each doe was given an injection of 0.4 mL of human chorionic gonadotrophin (400 IU) via the marginal ear vein. Three hours later, each doe was inseminated artificially with 0.3 mL of diluted semen from a proven donor buck using approximately 20E+06 motile sperm according to the procedure described by Vogin et al.
Duration of treatment / exposure:
Mice: 10 days
Rats: 10 days
Rabbits: 13 days
Frequency of treatment:
Daily
Duration of test:
Mice: 17 days
Rats: 20 days
Rabbits: 29 days
Dose / conc.:
16 mg/kg bw/day
Remarks:
Species: mice, rats, rabbits
Dose / conc.:
74.3 mg/kg bw/day
Remarks:
Species: mice, rats, rabbits
Dose / conc.:
345 mg/kg bw/day
Remarks:
Species: mice, rats, rabbits
Dose / conc.:
1 600 mg/kg bw/day
Remarks:
Species: mice, rats, rabbits
No. of animals per sex per dose:
Mice: Mated animals 24-30
Rats: Mated animals 25
Rabbits: Mated animals 20-22
Refer to tables 3 (mice) table 4 (rats) and table 5 (rabbits)
Control animals:
yes, sham-exposed
other: Asprin was used as the positive control in mice at a dose of 150 mg/kg and in rats at a dose of 250 mg/kg ... (see attached file)
Details on study design:
None specified
Maternal examinations:
Mice:
Body weights were recorded on Days 0, 6, 11, 15 and 17 of gestation.
All animals were observed daily for appearance and behaviour with particular attention to food consumption and weight in order to rule out any abnormalities which may have occurred as a result of anorexic effects in the pregnant female animal. The urogenital tract of each dam was examined in detail for anatomical abnormality.

Rats:
Body weights were recorded on Days 0, 6, 11, 15 and 20 of gestation.
All animals were observed daily for appearance and behaviour with particular attention to food consumption and weight in order to rule out any abnormalities which may have occurred as a result of anorexic effects in the pregnant female animal. The urogenital tract of each dam was examined in detail for anatomical abnormality.

Rabbits:
Body weights were recorded on Days 0, 6, 12, 18 and 29 of gestation.
All animals were observed daily for appearance and behaviour with particular attention to food consumption and weight in order to rule out any abnormalities which may have occurred as a result of anorexic effects in the pregnant female animal. The urogenital tract of each dam was examined in detail for anatomical abnormality.
Ovaries and uterine content:
Mice:
Number of implanation sites, resorption sites and live and dead foetuses were recorded.

Rats:
Number of implanation sites, resorption sites and live and dead foetuses were recorded.

Rabbits:
The number of corpora lutea, implanation sites, resorption sites and live and dead foetuses were recorded.
Fetal examinations:
Mice:
Body weights of live pups were recorded. All foetuses were examined for the presence of external congenital abnormalities. One third of the foetuses for each litter underwent detailed visceral examinations employing the Wilson technique. The remaining two-thirds were cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.

Rats:
Body weights of live pups were recorded. All foetuses were examined for the presence of external congenital abnormalities. One third of the foetuses for each litter underwent detailed visceral examinations employing the Wilson technique. The remaining two-thirds were cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.

Rabbits:
Body weights of live pups were recorded. All foetuses were examined for the presence of external congenital abnormalities. The live foetuses of each litter were then placed in an incubator for 24 h for the evaluation of neonatal survival. All surviving pups were sacrificed and all pups were examined for visceral abnormalities by dissection. All foetuses were then cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.
Statistics:
None specified
Indices:
None specified
Historical control data:
None specified
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
Not applicable
Dose descriptor:
NOAEL
Remarks:
Mice
Effect level:
1 600 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: no clearly discernable effects on nidation or on maternal or foetal survival.
Dose descriptor:
NOAEL
Remarks:
Rats
Effect level:
1 600 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: no clearly discernable effects on nidation or on maternal or foetal survival.
Dose descriptor:
NOAEL
Remarks:
Rabbits
Effect level:
1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: no clearly discernable effects on nidation or on maternal or foetal survival.
Abnormalities:
no effects observed
Reduction in number of live offspring:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Not applicable
Dose descriptor:
NOAEL
Effect level:
1 600 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: no clearly discernable effects on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.
Abnormalities:
no effects observed
Developmental effects observed:
no

Table 6: Fate summary for mice:

Group

Material

Dose**

Total

Surviving at term

Mated

Pregnant

Total

Pregnant1

341

Sham

0.0

25

22

25

22

342

Aspirin

150.0

25

19

25

19

343

FDA71 - 86

16.0

28

22

28

22

344

FDA71 – 86

74.3

24

22

24

22

345

FDA71 – 86

345.0

25

24

25

24

346

FDA71 - 86

1600.0

30

23

29

22

* positive control: 150 mg/kg

** administered as a water solution (10 mL per kg of body weight)

1) includes all dams examined at term

Table 7: Reproduction data for mice:

Group

341

342

343

344

345

346

Dose (mg/kg)

Sham

Aspirin**

16.0

74.3

345.0

1600.0

Pregnancies

Total No.

22

19

22

22

24

23

Died or aborted (before Day 17)

0

0

0

0

0

1

To term (on Day 17)

22

19

22

22

24

22

Live litters

Total No.*

21

19

22

21

24

21

Implant sites

Total No.

251

240

263

283

265

267

Average/dam*

11.4

12.6

12.0

12.9

11.0

12.1

Resorptions

Total No. *

19

8

5

12

21

14

Dams with 1 or more sites resorbed

6

5

4

2

9

7

Dams with all sites resorbed

1

-

-

1

-

1

Percent partial resorptions

27.3

26.3

18.2

9.09

37.5

31.8

Percent complete resorptions

4.55

-

-

4.55

-

4.55

Live foetuses

Total No.

229

224

255

268

243

250

Average/dam*

10.4

11.8

11.6

12.2

10.1

11.4

Sex ratio (M/F)

1.16

1.07

0.90

1.00

0.94

1.02

Dead foetuses

Total*

3

8

3

3

1

3

Dams with 1 or more dead

2

6

2

3

1

3

Dams with all dead

-

-

-

-

-

-

Percent partial dead

9.09

31.6

9.09

13.6

4.17

13.6

Percent all dead

-

-

-

-

-

-

Average Foetus weight, g.

0.89

0.87

0.86

0.87

0.91

0.88

* includes only those dams examined at term

** positive control, 150.0 mg/kg

Table 8: Fate summary for rats:

Group

Material

Dose**

Total

Surviving at term

Mated

Pregnant

Total

Pregnant1

341

Sham

0.0

25

25

25

25

342

Aspirin

250.0

25

23

25

23

343

FDA71 - 86

16.0

25

21

25

21

344

FDA71 – 86

74.3

25

23

25

23

345

FDA71 – 86

345.0

25

23

25

23

346

FDA71 - 86

1600.0

25

21

25

21

* positive control 250 mg/kg

** administered as a water solution

1) includes all dams examined at term

Table 9: Reproduction data for rats.

Group

341

342

343

344

345

346

Dose

Sham

Aspirin**

16.0

74.3

345.0

1600.0

Pregnancies

Total No.

25

23

21

23

23

21

Died or aborted (before Day 20)

0

0

0

0

0

0

To term (on Day 20)

25

23

21

23

23

21

Live litters

Total No.*

25

18

21

23

23

21

Implant sites

Total No.

279

231

229

270

253

233

Average/dam*

11.2

10.0

10.9

11.7

11.0

11.1

Resorptions

Total No. *

4

62

4

7

7

4

Dams with 1 or more sites resorbed

3

11

3

3

2

3

Dams with all sites resorbed

-

4

-

-

-

-

Percent partial resorptions

12.0

47.8

14.3

13.0

8.70

14.3

Percent complete resorptions

-

17.4

-

-

-

-

Live foetuses

Total No.

275

168

224

263

246

229

Average/dam*

11.0

7.30

10.7

11.4

10.7

10.9

Sex ratio (M/F)

1.07

1.06

0.87

1.07

1.18

0.75

Dead foetuses

Total*

-

1

1

-

-

-

Dams with 1 or more dead

-

1

1

-

-

-

Dams with all dead

-

1

-

-

-

-

Percent partial dead

-

4.35

4.76

-

-

-

Percent all dead

-

4.35

-

-

-

-

Average Foetus weight, g.

3.68

2.39

3.92

3.94

3.77

4.04

* includes only those dams examined at term

** positive control: 250 mg/kg

Table 10: Fate summary for rats

Group

Material

Dose**

mg/kg

Total

Surviving at term

Mated

Pregnant

Total

Pregnant1

341

Sham

0.0

18

13

18

13

342

6-AN*

2.5

20

10

19

10

343

FDA71 - 86

16.0

22

14

19

11

344

FDA71 - 86

74.3

22

13

21

13

345

FDA71 - 86

345.0

20

13

19

12

346

FDA71 - 86

1600.0

20

14

15

11

* positive contorl: 2.5 mg/kg of 6 aminonicotinamide dosed on Day 9

** administered as a water solution.

1) includes all dams examined at term.

Table 11: Reproduction data for rabbits

Group

341

342

343

344

345

346

Dose

Sham

6-AN**

16.0

74.3

345.0

1600.0

Pregnancies

Total No.

13

10

14

13

13

14

Died or aborted (before Day 29)

0

1

3

0

1

3

To term (on Day 29)

13

10

11

13

12

11

Corpora lutea

Total No.

174

122

195

173

134

139

Average/dam mated

9.67

6.42

9.29

8.65

7.05

7.72

Live litters

Total No.

12

10

11

13

10

10

Implant sites

Total No.

69

56

60

70

68

62

Average/dam

5.31

5.60

5.45

5.38

5.67

5.64

Resorptions

Total No.*

4

2

4

7

9

4

Dams with 1 or more sites resorbed

3

1

3

3

6

1

Dams with all sites resorbed

1

-

-

-

2

1

Percent partial resorptions

23.1

10.0

27.3

23.1

50.0

9.09

Percent complete resorptions

7.69

-

-

-

16.7

9.09

Live foetuses

Total No.*

65

54

56

63

59

58

Average/dam

5.00

5.40

5.09

4.85

4.92

5.27

Sex ratio (M/F)

0.86

0.74

1.33

1.30

1.36

1.42

Dead foetuses

Total No.*

-

-

-

-

-

-

Dams with 1 or more dead

-

-

-

-

-

-

Dams with all dead

-

-

-

-

-

-

Percent partial dead

-

-

-

-

-

-

Percent all dead

-

-

-

-

-

-

Average foetus weight

38.2

33.8

37.8

38.2

39.9

42.4

* included only those dams examined at term

** positive control: 2.5 mg/kg of 6-aminonicotinamide dosed on Day 9

Conclusions:
Mice:
Administration of up to 1600 mg/kg (body weight) of the test material to pregnant mice for 10 consecutive days had no clearly discernable effects on nidation or on maternal or foetal survival.

Rats:
The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernable effects on nidation or on maternal or foetal survival.

Rabbits:
up to 1600 mg/kg (body weight) of the test material to pregnant rabbits for 13 consecutive days had no clearly discernable effects on nidation or on maternal or foetal survival.

All species: The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 600 mg/kg bw/day
Study duration:
subacute
Species:
other: mice, rat, rabbit
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Toxicity to reproduction: other studies

Description of key information

In a study cited in the available literature (Paterson et al 1979) A reproductive trial involved 31 sows and 27 gilts of Hampshire x Yorkshire x Duroc breeding. Sows and gilts were grouped separately on the basis of ancestry and weight. Outcome groups were randomly assigned to the three treatments. The three treatments consisted of sodium sulfate added to water to give sulfate and total dissolved solids in ppm as follows (1): 320, 620, (2) 1820, 2840 and (3) 3320, 5060.

There were no significant differences in gestation or lactation gains and number or weight of pigs at birth or at weaning. Fecal consistency was normal in all treatments. Water consumption did not differ during gestation but increased during lactation as salt level increased. These results suggest that sulfates up to and including 3320 ppm in water have no significant effect on reproduction in the gilt or sow.

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Supporting study only
Qualifier:
no guideline available
Principles of method if other than guideline:
The experiment was conducted to investigate the effects of high sulphate waters given to swine during gestation and lactation
GLP compliance:
not specified
Type of method:
in vivo
Species:
pig
Sex:
female
Details on test animals and environmental conditions:
During gestation all animals were housed in uninsulated wooden colony type houses located in dry lots. Feed was restricted to 1.8 kg per head daily and fed in individual feeding stalls. Water was availabel ad libitum. Sows were allowed access to feed and water each morning adn evening for 2.0 and 1.5 hr respectively. Saline water was available in the creep area for pigs after 10 days of age
Route of administration:
oral: drinking water
Details on analytical verification of doses or concentrations:
Sulfate content was determined weekly by a turbidimetric method. The average and their standard deviations for the entire experimental period were as follows: control 320 ± 24 ppm; low sulfate, 1790 ± 35 ppm and high sulfate, 3298 ± 139 ppm.
Duration of treatment / exposure:
30 days postbreeding through 28 days lactation
Frequency of treatment:
Water was added ad libitum
Dose / conc.:
320 ppm
Dose / conc.:
620 ppm
Dose / conc.:
1 820 ppm
Dose / conc.:
2 840 ppm
Dose / conc.:
3 320 ppm
Dose / conc.:
5 060 ppm
Details on study design:
The reproductive trial involved 31 sows and 27 gilts of Hampshire x Yorkshire x Duroc breeding. Sows and gilts were grouped separately on the basis of ancestry and weight. Outcome groups were randonly assigned to the three treatments. The three treatments consisted of sodium sulfate added to water to give sulfate and total dissolved solids in ppm as follows (1): 320, 620, (2) 1820, 2840 and (3) 3320, 5060.
Dose descriptor:
NOAEL
Effect level:
3 320 ppm
Remarks on result:
other: Sulfates up to and including 3320 ppm in water have no significant effect on reproduction in the gilt or sow.

Table 1: Effect of sulfate content of water on reproductive performance

Parameter

Added sulfates (ppm)

Gilts

Sows

0

1500

3000

No. litter

12

13

14

16

23

Avg gestation gain, kga

30.2

27.5

26.0

41.0

18.6

Avg lactation gain, kgb

1.5

-5.5

1.7

5.5

-7.0

Water consumption, litters/day

Gestation

13.3

11.2

10.6

15.1

9.2

Lactation

13.6

14.2

16.8

14.4

15.5

Pigs/litter

Total

11.1

10.9

10.0

9.8

11.7

Live

9.6

10.0

8.2

8.7

9.9

Avg pig birth weight, kgb

1.4

1.4

1.5

1.3

1.5

Avg litter birth weight, kg

13.5

13.5

11.8

11.6

14.2

No. pigs at 28 days

6.7

6.9

6.3

6.5

6.8

28-day pig weight, kg

6.1

6.2

6.3

6.1

6.4

28-day litter weight, kg

40.4

42.2

40.2

39.5

42.3

aSignificant difference (P 0.01) between gilts and sows

bSignificant difference (P 0.05) between gilts and sows

Conclusions:
Sulfates up to and including 3320 ppm in water have no significant effect on reproduction in the gilt or sow.

Justification for classification or non-classification

Calcium sulfate is not toxic to reproduction and has no effect on fertility or development. Consequently, it does not warrant classification under CLP.