Methylammonium chloride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL was considered to be 500 mg/kg bw/day for P1 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.

Link to relevant study records

Reference

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

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

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

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

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

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

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.

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: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

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: oestrous cycle:

effects observed, treatment-related

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Reproductive function: estrous cycle: 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.

Reproductive performance: No effect on Number of Pups/Litter were observed in treated female rats.

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

Critical effects observed:

not specified

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

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Viability: No effect on viability of treated pups were observed till day 4 of lactation as compared to control.

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

Critical effects observed:

not specified

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

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

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

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

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.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is Klimisch 4 and from study report

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Toxicity to reproduction: oral

In study, Methanaminium chloride has been investigated for reproductive toxicity. Study based on in vivo experiment in rodents, i.e. most commonly in rats for Methanaminium chloride.

In a experimental study by American Chemistry Council (U.S. Environmental Protection Agency, Document Processing Centre, Mail Code 7407, April 6, 2006), 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 to Screen repeated dose reproduction –development toxicity. 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 P1 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.

Thus, based on the above study on Methanaminium chloride and by applying the weight of evidence, Methanaminium chloride can be “Not classified” for reproductive toxicity.

Effects on developmental toxicity

Description of key information

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 Methylaminehydrochloride (Methanaminium chloride) orally by gavage for 110 days.

Link to relevant study records

Reference

Endpoint:

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

Qualifier:

according to guideline

Guideline:

other: OECD 422 guideline (combined repeat dose study with a reproductive/developmental screen)

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

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

Species:

rat

Strain:

not specified

Details on test animals or test system and environmental conditions:

Sex: Male and female

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

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Length of cohabitation: 2 weeks

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

Duration of test:

110

Remarks:

0, 250, 500 and 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 available

Maternal examinations:

Body weight and food consumption, gross pathology and histopathology was observed.

Ovaries and uterine content:

Implantation sites and ovarian corpora lutea also examined.

Fetal examinations:

Pup viability, individual pup weights, litter sizes.and clinical signs were observed at birth and on lactation day 4.

Statistics:

No data available

Indices:

Mean Number of Pups/Litter and Offspring viability indices was observed on day 0 and 4 of lactation were examined.

Historical control data:

No data available

Clinical signs:

not specified

Dermal irritation (if dermal study):

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:

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.

Number of abortions:

not specified

Pre- and post-implantation loss:

effects observed, treatment-related

Total litter losses by resorption:

effects observed, treatment-related

Early or late resorptions:

not specified

Dead fetuses:

not specified

Changes in pregnancy duration:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified

Changes in number of pregnant:

not specified

Other effects:

not specified

Details on maternal toxic effects:

Reproductive function: estrous cycle: 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.

Reproductive performance: No effect on Number of Pups/Litter were observed in treated female rats.

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

body weight and weight gain

food consumption and compound intake

pre and post implantation loss

other: No adverse effect

Fetal body weight changes:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

not specified

Skeletal malformations:

not specified

Visceral malformations:

not specified

Other effects:

not specified

Details on embryotoxic / teratogenic effects:

Viability: No effect on viability of treated pups were observed till day 4 of lactation as compared to control.

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effect on Number of Pups/Litter and viability

Abnormalities:

not specified

Developmental effects observed:

no

Treatment related:

not specified

Relation to maternal toxicity:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

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

Conclusions:

NOAEL was considered to be 500 mg/kg bw/day for P1 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 with Methylamine hydrochloride (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, 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 develpmental toxicity was observed in treated pups such as on viability 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 P1 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.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is Klimisch 4 and from study report

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

Developmental toxicity: Oral

In study, Methanaminium chloride has been investigated for developmental toxicity. Study based on in vivo experiment in rodents, i.e. most commonly in rats for Methanaminium chloride.

In a repeated dose reproduction –development toxicity study, male and female rats were treated with Methylaminehydrochloride (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 P1 generation and 1000 mg/kg bw/day for F1 generation when male and female rats were treated with Methylaminehydrochloride (Methanaminium chloride) orally by gavage for 110 days.

Thus, based on the above study on Methanaminium chloride and by conceding the weight of evidence, Methanaminium chloride can be “Not classified” for developmental toxicity. 

Justification for classification or non-classification

Based on the above study on Methanaminium chloride and by conceding the weight of evidence, Methanaminium chloride can be “Not classified” for reproductived and Developmental toxicity.