Calcium sulfate

Endpoint summary

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 for cross-reference:

reference to same study

Qualifier:

according to guideline

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 or test system 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

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 or test system 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	Pregnant^1
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	Pregnant^1
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	Pregnant^1
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 or test system 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, kg^a	30.2	27.5	26.0	41.0	18.6
Avg lactation gain, kg^b	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, kg^b	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.