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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
multi-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
In accordance with Section 1.2 of REACH Annex XI, testing does not appear to be scientifically necessary as the weight of evidence indicates no concern for reproductive (fertility) effects from sulfur (conclusions from EFSA evaluations on food additives of sulfur-containing substances and EPA assessments for sulfur oxides and Cosmetic Ingredient Review of Sodium Sulfate) and therefore further testing on vertebrate animals is not warranted.

Sulfur is an inorganic element, which in its various forms (elemental, oxidised and reduced) accounts for about 1.9% of the total weight of the earth. Sulfur-deficient environments are rare in nature with chronic exposure to sulfur being the natural state. It is generally recognised as safe (40 CFR §180.2) by the US EPA and "since it does not give rise to metabolites other than such are well known to be intermediary or end products of mammalian metabolic reactions, the intent of chronic testing requirements do not apply to elemental sulfur and its possible metabolites."

In general, sulfur is an essential element in the metabolism of all living organisms, thus chronic exposure to sulfur is the natural state. More specifically, sulfur is unreactive and insoluble. Systemic effects were absent after subacute and subchronic oral exposure and subacute dermal exposure. Although sulfur can be absorbed both dermally and orally, it is mainly expected to be rapidly excreted. In the main, elemental sulfur is expected to be metabolised by plants rather than animals, with human intake of sulfur usually in the form of sulfur-containing amino acids, as well as sulfates and sulfites that may be present in many foods and beverages. Sulfur is only metabolised by intestinal bacteria; there are indications of absorption of metabolites but which are most likely endogenous to the body (e.g. well known to be intermediary or end products of mammalian metabolic reactions). The expectation that no effects on developmental toxic effects will occur as a consequence of sulfur exposure is supported by the long-standing use of sulfur in topically applied, pharmaceutical formulations and as a pesticide and the absence of developmental toxicity.

The weight of evidence looks at the available data on the forms of sulfur expected to be relevant to man, i.e. oxides of sulfur, sulfates and sulfites.

Data source

Reference
Reference Type:
review article or handbook
Title:
Final Amended Safety Assessment of Sodium Sulfate as Used in Cosmetics
Author:
Cosmetic Ingredient Review Expert Panel
Year:
2016
Bibliographic source:
Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200, Washington, DC 20036-4702

Materials and methods

Test guideline
Guideline:
other: review of tests by various methods on different sulphur containing substances
GLP compliance:
no
Remarks:
Review article; GLP not applicable

Test material

Constituent 1
Chemical structure
Reference substance name:
Sulfur
EC Number:
231-722-6
EC Name:
Sulfur
Cas Number:
7704-34-9
Molecular formula:
S
IUPAC Name:
sulfur
Test material form:
solid

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Remarks on result:
other: No adverse effects on reproduction parameters expected for sulfur containing compounds

Results: F1 generation

Effect levels (F1)

Remarks on result:
other: No adverse effects on reproduction parameters expected for sulfur containing compounds

Overall reproductive toxicity

Reproductive effects observed:
no

Applicant's summary and conclusion

Executive summary:

The CIR panel noted that there were no abnormal results for reproductive and developmental endpoints for rats administered Sodium Sulfate by gavage at dose rates up to 1000 mg/kg/day. NOEL for reproductive/developmental toxicity endpoints was 1000 mg/kg/day.  

An OECD guideline 421 screening study was conducted on Wistar rats at doses of 0, 100, 300 and 1000 mg/kg/day administered by oral gavage. Animals (both sexes, 10 rats/sex/group) were dosed for 14 -days pre-pairing, for the duration of parining (up to 14 days) and either 1 day before necropsy after at least 28 days (males) or 4 days post partum (females). No effects on either general toxicity or reproductive parameters (including reproductive function (sperm measures), reproductive performance, fertility index, conception rate, duration of gestation, corpora lutea count, implantation rate, post-implantation loss, duration of gestation, and litter size) were noted and the NOEL was set at 1000 mg/kg/day.