Methoxyammonium chloride

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: Screening for reproductive toxicity (fertility)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Results on reproductive organs are part of a 3 month repeated dose study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Principles of method if other than guideline:

Examination of male and female reproductive organs was part of a 3 month repeated dose study.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(hydroxylammonium) sulphate

EC Number:

233-118-8

EC Name:

Bis(hydroxylammonium) sulphate

Cas Number:

10039-54-0

Molecular formula:

H3NO.1/2H2O4S

IUPAC Name:

bis(hydroxyammonium) sulfate

Details on test material:

- Name of test material (as cited in study report): Hydroxylammoniumsulfat (HAS)
- Analytical purity: >= 99 %
- Lot/batch No.: 84/389
- Stability under test conditions: was ensured during the study period

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach a.d. Riss, Germany
- Age at study initiation: 42 days
- Average weight at study initiation: males ca. 117 g; females ca. 136 g
- Housing: individually in V2A wire mesh cages, type DK III (Becker & Co. Castrop-Rauxel, Germany)
- Diet: Kliba-Haltungsdiaet Ratte/Maus/Hamster 343 Mehl (Klingentalmuehle AG, Kaiseraugst, Switzerland), ad libitum
- Water: Milli-Q-Reinstwasser, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70 %
- Air changes: fully air-conditioned rooms
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

other: Mili-Q extra pure water

Details on exposure:

Wistar rats (10 animals/sex/dose group) had been exposed via drinking water for over 3 months at concentrations of 10, 50, and 250 ppm according to dose levels of about 0.9, 4, and 21 mg/kg bw/d.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

For homogeneity and concentration control analyses, each samples of all concentrations were drawn at the start of the study, after 6 weeks and towards at the end of the administration period after 12 weeks of the study. The analysis of the amount of the test material in the drinking water was determined by photometry.

Duration of treatment / exposure:

Exposure period: 90 d

Frequency of treatment:

ad libitum

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

250 mg/L drinking water

Remarks:

ca. 21 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

50 mg/L drinking water

Remarks:

ca. 4 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

10 mg/L drinking water

Remarks:

ca. 0.9 mg/kg bw/day

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: pretests

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

Sperm parameters (parental animals):

Parameters examined in male parental generations: testis weight

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Endocrine findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

Details on results (P0)

The test substance does not interfere with reproductive organ weights and morphological integrity at dose levels of up to and including 250 ppm according to a daily intake of approximately 21 mg/kg bw/day . The NOAEL for systemic adverse effects of this study was 0.9 mg/kg bw/d for both sexes based on findings of hemolytic anemia with methemoglobinemia and changes in organ weight as well as histopathological changes in spleen and liver at higher dosages.

Effect levels (P0)

1

Dose descriptor:

NOAEL

Remarks:

general toxicity

Effect level:

0.9 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

haematology

organ weights and organ / body weight ratios

histopathology: non-neoplastic

2

Dose descriptor:

NOAEL

Remarks:

reproductive organs

Effect level:

>= 21 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: No interference of the test material with reproductive organ weights and morphological integrity

Results: F1 generation

Effect levels (F1)

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Within the scope of a 90 days study, absolute and relative weights of testes were examined. In treated animals, they were not different from the control, while there was a distinct morphologic response in the spleen, indicating that critical doses were exceeded. There were no treatment-related macroscopic changes in the testes. Ovaries were not considered.

Applicant's summary and conclusion

Conclusions:

The test substance does not interfere with reproductive organ weights and morphological integrity at dose levels of up to and including 250 ppm according to a daily intake of approximately 21 mg/kg bw/day . The NOAEL for systemic adverse effects of this study was 0.9 mg/kg bw/d for both sexes based on findings of hemolytic anemia with methemoglobinemia and changes in organ weight as well as histopathological changes in spleen and liver at higher dosages.

Executive summary:

Informations related to reproductive organs can be derived from the data of this repeated dose toxicity study, during which Wistar rats (10 animals/sex/dose group) had been exposed to hydroxylammonium sulfate (purity > 99%) via drinking water for over 3 months at concentrations of 10, 50, and 250 ppm according to dose levels of about 0.9, 4, and 21 mg/kg bw/d . Organ weight determinations of testes at all dose levels as well as macro- and microscopic evaluations of the testes at the highest dose level (250 ppm) had been performed for the male sex, whereas with females only macro- and microscopic evaluations had been performed for the uterus and the ovary at the highest dose level (250 ppm). At the end of the study for neither of these parameters any substance related changes could be detected. It is concluded from this study that the test substance does not interfere with reproductive organ weights and morphological integrity at dose levels of up to and including 250 ppm according to a daily intake of approximately 21 mg/kg bw (NOAEL). The NOAEL for systemic adverse effects of this study was 0.9 mg/kg bw/d for both sexes based on findings of hemolytic anemia with methemoglobinemia and changes in organ weight as well as histopathological changes in spleen and liver at higher dosages.