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Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity – Effects on fertility

In a chronic feeding study, male and female F344/N rats were given doses of 1500, 5000, and 15000 ppm of manganese (II) sulfate monohydrate (actual dose received: 60, 200, and 615 mg/kg/day for males and 70, 230, and 715 mg/kg/day for females, respectively). No adverse effects in male or female reproductive organs were reported. Based on the absence of any adverse effects related to the test substance, a No Observed Adverse Effect Level (NOAEL) for test item of 15000 ppm (actual dose received: 615 mg/kg/day for males and 715 mg/kg/day for females (200 and 233 mg Mn/kg/day, respectively) was concluded for male and female rats.

In a chronic feeding study, male and female B6C3F1 mice were given doses of 1500, 5000, and 15000 ppm of manganese (II) sulfate monohydrate (actual dose received: 160, 540, and 1800 mg/kg/day for males and 200, 700, and 2250 mg/kg/day for females, respectively). No adverse effects in male or female reproductive organs were reported. Based on the histopathological findings in the thyroid (follicular dilatation and focal hyperplasia), decreased final body weight in females, and haematological findings in the male mice at the 15000 ppm dose level, a No Observed Adverse Effect Level (NOAEL) for test item of 5000 ppm (actual dose received: 540 mg/kg/day for males and 700 mg/kg/day for females (172.8 and 224 mg Mn/kg/day, respectively)) was concluded for male and female mice.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity – Developmental toxicity

In a supporting study female weanling Sprague-Dawley rats were randomly divided in six groups with 17 animals per group and fed manganese sulfate in the diet at 0, 4, 24, 54, 154, 504 and 1004 mg/kg dry diet (Järvinen & Ahlström, 1975). After 8 weeks they were mated with males of the same strain and after 21 days the animals and fetuses were killed and examined. No treatment related effects were seen on number and percent of live and dead foetuses, resorptions and pre- and post-implantation losses. No gross malformation, bone structure abnormality or altered fetal weight was observed. No information on the sex ratio given. An increase in fetal manganese concentration could only be seen in the highest dose (1004 mg/kg). There was no maternal toxicity.

In accordance with regulation 1907/2006 (EC), Annex XI, Section 1, the standard testing regime of Annexes VII-X may be adopted in case testing does not appear scientifically necessary. Specifically, a weight-of-evidence evaluation can be performed to demonstrate that evidence from several independent sources of information leading to the assumption/conclusion that a substance either has or has not a particular dangerous property, while the information from each single source alone is regarded insufficient to support this notion.

In the case of manganese phosphate, the registrant is of the opinion that sufficient weight-of-evidence is available to demonstrate an absence of reproductive toxicity (developmental toxicity screening assay) and that any further testing on vertebrate animals should be omitted.

Manganese shows a low toxicological activity (i) in the two 2-year oral repeated dose toxicity studies with manganese sulfate in rats and mice indicated absolutely no effects whatsoever on reproduction up to doses of 700 mg/kg bw/day respectively, (ii) low order of toxicity is manifested in an absence of concern in a developmental toxicity study in rats with manganese sulfate.

Overall, the conduct of a reproductive toxicity study (developmental toxicity screening assay) cannot be expected to contribute any relevant information to the assessment of (otherwise negative) information on reproduction toxicity. As a result, the need for such testing is waived in accordance with regulation (EC) 1907/2008, Annex XI, Section 1.2.

Justification for classification or non-classification

There is no reliable equivocal animal evidence to link MnSO4 with reproductive toxicity via relevant routes of exposure. The NTP (1993) report (see IUCLID section 7.5.1) showed no effect on the testes of rats exposed orally for up to 2 years. A study on workers (Lauwerys et al., 1985) showed no effects on reproductive performance. There is no reliable evidence to suggest that MnSO4 is a developmental toxicant.Järvinen R & Ahlström A (1975) found no adverse developmental effects via the oral route in a rat study