Sodium sulphate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

The study R. Ceccatelli 2010, is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item Sodium Sulphate to rats. Sodium Sulphate was administered in highly purified water as vehicle at dosages of 100, 300, and 1000 mg/kg body weight/day, and controls received the vehicle only. Sodium Sulphate was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. In absence of any effect the general NOEL (No Observed Effect Level) was established at 1000 mg/kg/day. As no effects were observed, the NOEL (No Observed Effect Level) for reproduction/ developmental toxicity was considered to be 1000 mg/kg/day.

Short description of key information:

Based on OECD 421 As no effects were observed, the NOEL (No Observed Effect Level) for reproduction/ developmental toxicity was considered to be 1000 mg/kg/day.

Effects on developmental toxicity

Description of key information

Based on OECD 421 as no effects were observed, the NOEL (No Observed Effect Level) for reproduction/ developmental toxicity was considered to be 1000 mg/kg/day.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

The study R. Ceccatelli 2010 is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item Sodium Sulphate to rats. Sodium Sulphate was administered in highly purified water as vehicle at dosages of 100, 300, and 1000 mg/kg body weight/day, and controls received the vehicle only. Sodium Sulphate was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. In absence of any effect the general NOEL (No Observed Effect Level) was established at 1000 mg/kg/day. As no effects were observed, the NOEL (No Observed Effect Level) for reproduction/ developmental toxicity was considered to be 1000 mg/kg/day.

Seidenberg et al., 1986 examined the developmental effects of sodium sulfate in the mouse as part of a validation effort of a developmental screening test. The test substance was administered (2800 mg/kg/day) by gavage on gestation days 8 through 12. No mortality, an unchanged average weight gain, and normal number of litters and neonates/litter were found. A 100 % perinatal survival was found, with an increased postnatal weight at day 1, normal weight at day 3 in the absence of externally visible abnormalities. In second paper of Seidenberg et al, 1987 the results are summarised of this validation test, the outcome of the screening test was considered positive for sodium sulfate, based solely on the increased postnatal weight on day 1 post-partum. However, the significance of such an effect, in the absence of any other effect, is unclear and the reasons for taking this as a positive result are not given.

A developmental / teratogenicity study from P&G (1976) was designed to evaluate the embryotoxic and teratogenic potential of sodium sulphate and a mixture with sodium sulphate. The two test substances when administered to albino rats by oral intubation from Day 6 through Day 12 (13 day sacrifice) or through Day 15 (19 day sacrifice) of gestation at levels of 160 mg/kg bw per day of the test substance of concern (test substance 1, sodium sulphate) and at levels of 50, 100, and 200 mg/kg bw per day of the other tested substance (test substance 2, mixture).

Criteria evaluated for compound effect included maternal body weights, weight gain, food consumption, appearance and behavior, survival rates, pregnancy rates, and reproduction data; and embryo and fetal viability and development.

No effects attributable to the administration of either test substance were noted in comparisons of maternal body weight and food consumption values, appearance and behavior, survival rates, pregancy rates, or implantation efficiencies. In addition, no compound-related differences were noted in evaluations of embryo or fetal viability, or fetal size, sex, and development. Therefore, test substance 1 (Sodium sulphate), when administered to rats at a level of 160 mg/kg, and test substance 2 (mixture with sodium sulphate), when administered to rats at a level up to 200 mg/kg, were considered to be non-teratogenic and non-embryotoxic.

In the study of Arcuri and Gautieri 1973 reported teratogenic effects of morphine sulfate, atropine sulfate and physostigmine sulfate, sodium sulfate served as anion control, with sodium chloride as negative control. The study was well documented, with various endpoints (clinical observations, maternal weight ratio, uterine left/right horn fetal ratio and resorption ration, fetal weight, sex ratio, skeletal abnormalities, soft tissue abnormalities, more specifically exencephaly, cryptorchid test and axial skeletal fusions, but covered only the 8-9 day period of gestation for exposure and the dose of 60 mg/kg was relatively small. There was a statistically significant increase in skeletal abnormalities, described as delayed ossification in the phalanges, sternebrae and skull. Such variations are quite common in tests with rodents and, in the absence of skeletal malformations, generally not regarded as indicative of developmental toxicity. No abnormalities for any of the other endpoints were reported.

Justification for classification or non-classification

The available data give no indication that sodium sulfate is toxic for reproduction. With regard to the natural occurrence of the substance in the body, developmental toxicity is also very unlikely. Sodium sulphate should not be classified for reproduction and developmental toxicity.

Based on the results of the reproduction/developmental screenings test and the developmental toxicity/teratogenicity studies, sodium sulphate does not need to be classified for toxic to reproduction according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.