Registration Dossier
Registration Dossier
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EC number: 209-795-0 | CAS number: 593-51-1
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental 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:
- Data is from U.S. Environmental Protection Agency report
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- 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-devp. Screen of Methylamine hydrochloride in rat
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- 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
- Reference substance name:
- Methylamine hydrochloride
- IUPAC Name:
- Methylamine hydrochloride
- Details on test material:
- - Name of test material: Methylamine hydrochloride
- Molecular formula: - CH5N.ClH
Molecular weight: 67.5184 g/mol
- Smiles notation: C[NH3+].[ClH-]
- InChl: 1S/CH5N.ClH/c1-2;/h2H2,1H3;1H
- Substance type: Organic
Constituent 1
Constituent 2
- Specific details on test material used for the study:
- - Name of test material: Methylamine hydrochloride (MAH)
- IUPAC name: Methanaminium chloride
- Molecular formula: CH5NCl H
- Molecular weight: 67.5184 g/mole
- Substance type: Organic
Test animals
- Species:
- rat
- Strain:
- not specified
- Details on species / strain selection:
- No data available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Methylamine hydrochloride was dissolved in water to give a dose of 0, 250, 500 and 1000 mg/Kg bw
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
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 available
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on mating procedure:
- - Length of cohabitation: 2 weeks
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Total:110
Premating period -71 days
Mating period-14 days
Gestation period-21 days
Postpartum day -4. - Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
Doses / concentrations
- Remarks:
- 0, 250, 500 and 1000 mg/kg bw/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 available
- Positive control:
- No data available
Examinations
- Parental animals: Observations and examinations:
- Body weight and food consumption was observed.
- Oestrous cyclicity (parental animals):
- Any irregularity in estrous cycle were observed.
Implantation sites and ovarian corpora lutea also examined. - Sperm parameters (parental animals):
- No data available
- Litter observations:
- Pup viability, individual pup weights, litter sizes.and clinical signs were observed at birth and on lactation day 4.
- Postmortem examinations (parental animals):
- Gross pathology and histopathology were examined.
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 - Postmortem examinations (offspring):
- No data available.
- Statistics:
- No data available.
- Reproductive indices:
- Corpora Luta Counts and Mean Number of Pups/Litter were examined.
- Offspring viability indices:
- Offspring viability indices was observed on day 0 and 4 of lactation.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, non-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:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Body weight: Significant reductions in body weight in P1 animals were observed at 1000 mg/kg/day. Weight gain of pregnant females was less at 1000 mg /kg/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: Significant reductions in food consumption were observed in P1 male and female rats.
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
Details on results (P1)
Reproductive performance: No effect on Number of Pups/Litter were observed in treated female rats.
Effect levels (P1)
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- reproductive function (oestrous cycle)
- reproductive performance
- other: No adverse effect
Target system / organ toxicity (P1)
- Critical effects observed:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- other: No adverse effect
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- no
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Any other information on results incl. tables
MATBRNAL GROUP: |
II-0 |
IV-0 |
VI-0 |
VIII-0 |
DOSAGB{MG/KG/DAY): |
0 |
250 |
500 |
1000 |
CORPORA LUTEA COUNTS |
14.8 |
14.5 |
15.1 |
11.4* |
Standard Deviation(No. in group) |
2.3(12) |
2.1(11) |
1.8 (12) |
3.3(10) |
MEAN NUMBER OF PUPS/LITTER |
|
|
|
|
Born |
12.8 |
13.2 |
13.9 |
9.8 |
Born Alive |
12.8 |
13.0 |
13.9 |
9.8 |
Day 4 |
12.8 |
12.0 |
13.9 |
9.7 |
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 500 mg/kg bw/day for P generation and 1000 mg/kg bw/day for F1 generation when male and female rats were treated with Methylamine hydrochloride (Methanaminium chloride) orally by gavage for 110 days.
- Executive summary:
In a repeated dose reproduction –development toxicity study, male and female rats were treated withMethylaminehydrochloride (Methanaminium chloride) in the concentration of0, 250, 500 and 1000 mg/kg/day orally by gavage in water. Test was conducted as per OECD 422. Significant decrease in body weight of P1 animals were observed at 1000 mg/kg/day. Weight gain of pregnant females was less at 1000 mg /kg/day from gestational day 1 to day 7 (87.5% of control) but similar to the other groups at intervals after gestational day 7. Significant reductions in food consumption were observed in P1 male and female rats. Similarly, reproductive toxicity was observed in treated female rats at 1000 mg/kg bw such as significant decrease in corpora lutea counts and subsequently lower implantation site counts and litter sizes were observed at 1000 mg/kg/day treated female rat. But, No effect on Number of Pups/Litter were observed in treated female rats. In addition, No effect on viability of treated pups were observed till day 4 of lactation as compared to control at 250, 500 and 1000 mg/kg bw/day. Therefore, NOAEL was considered to be 500 mg/kg bw/day for P generation and 1000 mg/kg bw/day for F1 generation whenmale and female rats were treated withMethylaminehydrochloride (Methanaminium chloride) orally by gavage for 110 days.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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