1-methylpiperidin-4-ol

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 National Technical Reports Library (NTRL)

Data source

Reference

Reference Type:

secondary source

Title:

Results of reproduction/ developmental toxicity screening test in wistar rats with 105-59-9

Author:

National Technical Reports Library

Year:

2010

Bibliographic source:

National Technical Reports Library, OTS0600173, March 18, 2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-methyliminodiethanol

EC Number:

203-312-7

EC Name:

2,2'-methyliminodiethanol

Cas Number:

105-59-9

Molecular formula:

C5H13NO2

IUPAC Name:

2,2'-(methylimino)diethanol

Test material form:

other: Liquid

Details on test material:

- Name of test material: N-METHYLDIETHANOLAMINE
- Molecular formula:C5H13NO2
- Molecular weight:119.163 g/mol
- Smiles notation :N(CCO)(CCO)C
- InChl: 1S/C5H13NO2/c1-6(2-4-7)3-5-8/h7-8H,2-5H2,1H3
- Substance type:Organic
- Physical state: Liquid

Test animals

Species:

rat

Strain:

Wistar

Details on species / strain selection:

Wistar [Crl:WI(HAN) Charles River, sulzfeld, Germany]

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

oral: gavage

Remarks on MMAD:

No data

Vehicle:

olive oil

Details on exposure:

No data

Details on mating procedure:

No data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

No data

Frequency of treatment:

daily

Details on study schedule:

About 2 weeks after the begining of treatment,F0 animals were mated to produce litter. Mating pairs were from same group

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

No data

Positive control:

No data

Examinations

Parental animals: Observations and examinations:

No data

Oestrous cyclicity (parental animals):

Yes

Sperm parameters (parental animals):

No data

Litter observations:

NO data

Postmortem examinations (parental animals):

No data

Postmortem examinations (offspring):

No data

Statistics:

No data

Reproductive indices:

No data

Offspring viability indices:

No data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

The parental animal of both the sexes in the high dose group (1000 mg/kg bw/day) showed salivation after treatment on several occasion

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight/body weight gain decreased in male for entire treatment and in females during premating, gestation and on post natal day 1-4.

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:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

effects observed, treatment-related

Description (incidence and severity):

For high dose post implantation loss(31 vs 6% in control) and decreased average litter size (4.6 vs 12.1 in control)

Reproductive function: sperm measures:

not specified

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

Average duration of pregnancy was slightly increased in high dose (22.8 vs 22.1 days in control) and 2 dams were unable to complete parturition at high dose

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

reproductive function (oestrous cycle)

reproductive performance

2

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

organ weights and organ / body weight ratios

reproductive function (oestrous cycle)

reproductive performance

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, treatment-related

Description (incidence and severity):

In high dose group Pup body weight decreased by 19%.

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

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

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

Urinalysis findings:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not examined

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not examined

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No observed adverse effect

Results: F2 generation

General toxicity (F2)

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

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

Urinalysis findings:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not examined

Developmental neurotoxicity (F2)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F2)

Developmental immunotoxicity:

not examined

Overall reproductive toxicity

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for the test compound 2,2'-(methylimino)diethanol for wistar rats (male/female) was determined to be 100 mg/kg bw/day.

Executive summary:

Reproduction/Developmental screening test in Wistar rats with2,2'-(methylimino)diethanol (CAS 105-59-9) was conducted according to OECD 421. The test substance was admimisterd to groups of 10 male and 10 female young wistar rats (F0 parental generation) dissolved in olive oil, via daily gavage. The doses were 0, 100, 300 and 1000 mg/ kg bw. About 2 weeks after the begining of treatment,F0 animals were mated to produce litter. Mating pairs were from same group. Pregnant females were allowed to give birth and offspring were brought up till postnatal day (PND) 4. The study was terminated with the sacrifice of the F1 animals on PND 4 and of lactating dams shortly thereafter.

The parental animal of both the sexes in the high dose group (1000 mg/kg bw/day) showed salivation after treatment on several occasion during the study. Body weight/body weight gaindecreased in male for entire treatment and in females during premating, gestation and on post natal day 1-4. Fertility remained unaffected.Relative Liver weight were increased dose dependently in all treatment groups. Pregnancy was unaffected at low and mid dose. For high dose post implantation loss(31 vs 6% in control) and decreased average litter size (4.6 vs 12.1 in control) was noted. Adittionally, the average duration of pregnancy was slightly increased in high dose (22.8 vs 22.1 days in control) and 2 dams were unable to complete parturition at high dose group.

No test substance related adverse clinical findings were noted at 300 and 100 mg/kg bw/day. 

Therefore, No Observed Adverse Effect Level (NOAEL) for the test compound2,2'-(methylimino)diethanolfor wistar rats (male/female) was determined to be 300 and 100 mg/kg bw/day.