Methylammonium chloride

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

Combined repeated dose repro-devp. Screen

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from NTRL report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

Combined repeated dose repro-developmental toxicity study was performed to determine the toxic nature of Methylamine hydrochloride upon repeated administration by oral route.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methylammonium chloride

EC Number:

209-795-0

EC Name:

Methylammonium chloride

Cas Number:

593-51-1

Molecular formula:

CH5N.ClH

IUPAC Name:

methanamine

Constituent 2

Reference substance name:

Methylamine hydrochloride

IUPAC Name:

Methylamine hydrochloride

Details on test material:

- Name of test material (as cited in study report): Methylamine hydrochloride
- Molecular formula (if other than submission substance): CH5N.Cl H

- Molecular weight (if other than submission substance): 67.5184 g/mol
- Substance type: Organic
- Physical state:
Purity No data available.

Specific details on test material used for the study:

- Name of test material: Methylamine hydrochloride (MAH)
- IUPAC name: Methanaminium chloride
- Molecular formula: CH5NClH
- Molecular weight: 67.5184 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: No data
- Impurities (identity and concentrations): No data

Test animals

Species:

rat

Strain:

not specified

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

No data

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The chemical was dissolved in water to give a dose range of 0, 250, 500 or 1000 mg/Kg bw

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Water
- Concentration in vehicle: 0, 250, 500, or 1000 mg/kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

Total: 110 days
Premating period -71 days
Mating period-14 days
Gestation period-21 days
Postpartum day -4

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

0, 250, 500, or 1000 mg/kg/day

No. of animals per sex per dose:

Total no of animals-96
0 mg/kg/day - 12 male and 12 female
250 mg/kg/day- 12 male and 12 female
500 mg/kg/day- 12 male and 12 female
1000 mg/kg/day- 12 male and 12 female

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Not specified
- Time schedule: Not specified
- Cage side observations checked in table [No.?] were included. Not specified

DETAILED CLINICAL OBSERVATIONS: Not specified
- Time schedule: Not specified

BODY WEIGHT: Yes
- Time schedule for examinations: Not specified

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations: Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified

HAEMATOLOGY: Not specified
- Time schedule for collection of blood: Not specified
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined. Not specified

CLINICAL CHEMISTRY: Not specified
- Time schedule for collection of blood: Not specified
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined. Not specified

URINALYSIS: Not specified
- Time schedule for collection of urine: Not specified
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined. Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not specified

IMMUNOLOGY: Not specified
- Time schedule for examinations: Not specified
- How many animals: Not specified
- Dose groups that were examined: Not specified
- Parameters checked in table [No.?] were examined. Not specified

OTHER: Not specified

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, Gross pathological examination was performed at terminal sacrifice.

HISTOPATHOLOGY: Yes, Uterine implantation sites and ovarian corpora lutea were counted in P1 females. A histological examination of all tissues saved was conducted for all animals in the control and 1000 mg/kg/day group. Tissue examination in the other groups was limited to relevant gross lesions and tissues demonstrating treatment-related histological effects at 1000 mg/kg/day.

Other examinations:

No data

Statistics:

Standard Deviation

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

Clinical signs and mortality: No data available

Body weight and weight gain: Significant reductions in body weight in P1

Animals was observed at 1000 mg/kg/day. Weight gain of pregnant females was less for the high-dose group (1000 mg /k g/day) from gestational day 1 to day 7 (87.5% of control) but similar to the other groups at intervals after gestational day 7.

Food consumption and compound intake: Significant reductions in food consumption parameters in P1 animals at 1000 mg/Kg day.

Food efficiency: No data available

Water consumption and compound intake: No data available

Opthalmoscopic examination: No data available

Haematology: No data available

Clinical chemistry: No data available

Urinanalysis: No data available

Neurobehaviour: No data available

Organ weights: No data available

Gross pathology: Significantly reduced corpora lutea counts and subsequently lower implantation site counts and litter sizes at 1000 mg/kg/day was observed

Histopathology: No data available

Effect levels

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant change was observed in body weight, food consumption, corpora lutea counts, implantation site counts and litter sizes.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The No Observed Adverse Effect Level (NOAEL) is considered to be 500 mg/kg/day for Methylamine hydrochloride in male and female rats by oral gavage.

Executive summary:

Combined repeated dose repro-developmental toxicity study was performed (NTRL, 2006) to determine the toxic nature of Methylamine hydrochloride ( IUPAC name: Methanaminium chloride) upon repeated administration by oral route. Groups of 12 rats of each sex per dose level were dosed with methylamine hydrochloride in water once daily by gavage at dose levels of 0, 250, 500, or 1000 mg/kg/day. Following a 71-day premating period, P1 males and females were co-housed for up to 2 weeks within their respective treatment groups to produce F1 litters. Dams were allowed to deliver and rear their offspring until postpartum day 4.  All P1 rats were given a gross pathological examination at terminal sacrifice. Uterine implantation sites and ovarian corpora lutea were counted in PI females. A histological examination of all tissues saved was conducted for all animals in the control and 1000 mg /kg /day group. Tissue examination in the other groups was limited to relevant gross lesions and tissues demonstrating treatment-related histological effects at 1000 mg/kg/day. Significant changes in body weight and food consumtion were observed at 1000 mg/kg/day. Significantly reduced corpora lutea counts and subsequently lower implantation site counts and litter sizes at 1000 mg/kg/day was observed. No significant changes were observed at 0, 250, or 500 mg/kg/day. The No Observed Adverse Effect Level (NOAEL) is considered to be 500 mg/kg/day for Methylamine hydrochloride in male and female rats by oral gavage.