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Toxicological information

Toxicity to reproduction

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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:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
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
Estrous 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 animals)

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
Description (incidence and severity):
Relative Liver weight were increased dose dependently in all treatment groups.
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 (P0)

Reproductive function: estrous 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)

open allclose all
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 (estrous cycle)
reproductive performance
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 (estrous 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: estrous 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.