Trimanganese tetraoxide

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A well documented study with a clearly defined scope and with sufficiently detailed materials and methods. However, there is no statement on impurity profile of the test material.

Data source

Reference

Reference Type:

publication

Title:

Assessment of the male reproductive system in the preweanling rat following Mn3O4 exposure

Author:

Laskey JW, Rehnberg GL, Hein JF, Laws SC & Edens FW

Year:

1985

Bibliographic source:

Journal of Toxicology and Environmental Health, 15: 339-350

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Long-Evans rat pups were dosed orally from birth to 21 days with particulate Mn3O4 at 0, 71 or 214 mg Mn/kg body weight/day. Hypothalamic, pituitary or testicular functions were determined by measuring the endogenous or stimulated serum concentration of follicle-stimulating hormone, luteinising hormone, and/or testosterone at 21 or 28 days of age were assessed. Body, testes, and seminal vesicles weight and tissue concentrations of Mn were also evaluated.

GLP compliance:

no

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Trimanganese tetraoxide

EC Number:

215-266-5

EC Name:

Trimanganese tetraoxide

Cas Number:

1317-35-7

Molecular formula:

Mn3O4

IUPAC Name:

trimanganese tetraoxide

Details on test material:

- Name of test material : Particulate Mn3O4
- Analytical purity: Not reported

Test animals

Species:

rat

Strain:

Long-Evans

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Blue Spruce Farms, Altmont, NY, USA

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 50 % sucrose solution

Details on exposure:

DOSE ADMINISTRATION
Animals were dosed at the rate of 1 µL/g body weight.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Animals were dosed once a day from day 1 to day 21 in both studies.

Frequency of treatment:

Animals were dosed daily

Duration of test:

21 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

71 other: µg Mn/g bodyweight

Remarks:

Nominal conc. (Study 1)

Doses / concentrations 2

Dose / conc.:

71 other: µg Mn/g body weights

Remarks:

Nominal conc. (Study 2)

Doses / concentrations 3

Dose / conc.:

214 other: µg Mn/g body weights

Remarks:

Nominal conc. (Study 2)

No. of animals per sex per dose:

Not reported

Control animals:

yes, concurrent vehicle

Details on study design:

Pregnant rats were received on day 1 of gestation. On day 1 postpartum litters were normalised to 8 pups/litter with at least 1 female per litter.

Statistics:

Data were analysed, where appropriate, by one- or two-way analysis of variance, linear regression, or Duncan's multiple comparison procedures.

Results and discussion

Any other information on results incl. tables

Study 1

No Mn-treatment-related effects were seen in bodyweights at 21 of 28 days of age. There was significant depression in testes weight at 21 days in animals receiving 71 µg Mn/g bodyweight, but this difference was not present at day 28. Mn concentrations in the liver and hypothalamus were 150 and 63% higher in the Mn-treated castrated rats when compared to the Mn-treated non-castrated rats.

No Mn-treatment-related effects were seen in the endogenous T, FSH, or LH serum concentrations. No treatment effects were seen in the serum FSH or LH concentrations following castration, in the serum FSH or T concentrations following 2 -hour LH-RH stimulation, or in the 2 -hour hCG-stimulated serum T concentration. Following 7 days of hCG stimulation, however, serum T concentration was significantly lower in the Mn-treated animals. Additionally, the 7 -day hCG treatment resulted in significant and comparable increases in body, testes, and seminal vesicles weight.

Study 2

Significant Mn dose-related depressions in bodyweight were noted at 28 days of age. Testicular growth in animals that received 7 days of hCG stimulation following 214 µg Mn/g bodyweight for 21 days was less that either control animals or animals that received 71 µg Mn/g bodyweight. Mn treatment (214 µg Mn/g bodyweight) resulted in depressed serum T concentration in animals following 7 days hCG stimulation. Neither FSH nor LH serum concentrations showed any Mn-treatment-related differences with any of the assessment procedures.

Applicant's summary and conclusion

Conclusions:

Excess oral exposure of test material, to the preweanling rat was found to cause subtle alterations in the reproductive axis and appeared to interfere with the synthesis of T. These effects are not thought to interfere with rodent fertility at chronic dietary levels up to 1100 ppm Mn.

Executive summary:

Rats were dosed orally from birth to 21 days with test material at 0, 71 or 214 µg Mn/g body weight/day. Hypothalamic, pituitary or testicular functions were determined by measuring the endogenous or stimulated serum concentration of follicle-stimulating hormone, luteinising hormone, and/or testosterone at 21 or 28 days of age were assessed. Body, testes, and seminal vesicles weight and tissue concentrations of Mn were also evaluated.

Only slight Mn treatment effects were seen in body and testes weights. No effects were seen either on unstimulated or stimulated FSH or LH serum concentrations. Although no Mn treatment effects were seen on endogenous or 2 hour human chorionic gonadotropin (hCG) stimulate serum T concentrations, there was a reduction in the serum T following 7 days of hCG stimulation. The hypothalamic Mn concentrations in animals with these reproductive effects were three times those where alterations in the dopaminergic pathway have been reported. However, no indication of hypothalamic or pituitary malfunction was found. These results suggest that the site of Mn damage that causes depression of sustained serum T concentrations is in the testicular Leydig cell.