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EC number: 203-406-8 | CAS number: 106-52-5
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
The No Observed Adverse Effect Level (NOAEL) for the test compound 1-Methyl-4-hydroxypiperidine for rats was estimated to be 303.9583 mg/kg bw/day.
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: as mentoned below
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 3.3
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 1-methylpiperidin-4-ol
- Molecular formula: C6H13NO
- Molecular weight: 115.175 g/mol
- Substance type: Organic
- Physical state: Liquid - Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- not specified
- Details on exposure:
- No data
- Details on mating procedure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- No data
- Frequency of treatment:
- No data
- Details on study schedule:
- No data
- No. of animals per sex per dose:
- No data
- Control animals:
- not specified
- Details on study design:
- No data
- Parental animals: Observations and examinations:
- No data
- Oestrous cyclicity (parental animals):
- No data
- 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
- 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
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 303.958 mg/kg bw/day (actual dose received)
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: Estimated
- 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
- 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: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- not specified
- Clinical signs:
- no effects observed
- 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:
- no effects observed
- Histopathological findings:
- not examined
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Remarks on result:
- not measured/tested
- 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:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) for the test compound 1-Methyl-4-hydroxypiperidine for rats was estimated to be 303.9583 mg/kg bw/day.
- Executive summary:
Reproductive toxicity study was estimated for the test chemical 1-Methyl-4-hydroxypiperidine using SSS QSAR prediction database, 2017. The study assumed the use of rats in study. The No Observed Adverse Effect Level (NOAEL) for the test compound 1-Methyl-4-hydroxypiperidine is found to be 303.9583 mg/kg bw/day.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
(((((("a"
or "b" or "c" or "d" or "e" )
and ("f"
and (
not "g")
)
)
and "h" )
and "i" )
and "j" )
and ("k"
and "l" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Aliphatic Amines by US-EPA New
Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Alcohol AND Piperidine AND
Saturated heterocyclic amine AND Saturated heterocyclic fragment by
Organic Functional groups
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Alcohol AND Overlapping groups
AND Piperidine AND Saturated heterocyclic amine AND Saturated
heterocyclic fragment by Organic Functional groups (nested)
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] AND
Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Amino,
aliphatic attach [-N<] AND Hydroxy, aliphatic attach [-OH] by Organic
functional groups (US EPA)
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Alcohol AND Amine AND
Heterocyclic compound AND Hydroxy compound AND Secondary alcohol AND
Tertiary aliphatic amine AND Tertiary amine by Organic functional
groups, Norbert Haider (checkmol)
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Iminium Ion
Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines
by DNA binding by OECD
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Michael addition OR Michael
addition >> P450 Mediated Activation to Quinones and Quinone-type
Chemicals OR Michael addition >> P450 Mediated Activation to Quinones
and Quinone-type Chemicals >> Alkyl phenols OR No alert found OR Schiff
base formers OR Schiff base formers >> Chemicals Activated by P450 to
Glyoxal OR Schiff base formers >> Chemicals Activated by P450 to
Glyoxal >> Ethanolamines (including morpholine) OR Schiff base formers
>> Chemicals Activated by P450 to Glyoxal >> Ethylenediamines
(including piperazine) OR SN1 >> Nitrenium Ion formation OR SN1 >>
Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as High (Class III) by Toxic hazard
classification by Cramer (original) ONLY
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Narcotic Amine by Acute aquatic
toxicity MOA by OASIS ONLY
Domain
logical expression index: "j"
Similarity
boundary:Target:
CN1CCC(O)CC1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "k"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -2.14
Domain
logical expression index: "l"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 1.7
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 303.958 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is from K2 prediction database
Additional information
Prediction model based estimation and data from read across have been summarized to determine the toxic nature of the test compound 1-Methyl-4-hydroxypiperidin to reproduction:
Reproductive toxicity study was estimated for the test chemical 1-Methyl-4-hydroxypiperidine using SSS QSAR prediction database, 2017. The study assumed the use of rats in study. The No Observed Adverse Effect Level (NOAEL) for the test compound 1-Methyl-4-hydroxypiperidine is found to be 303.9583 mg/kg bw/day.
From the data for read across, 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.
The weight of evidence data summarized suggests the chemical 1-Methyl-4-hydroxypiperidine to be not likely classified for reproductive toxicity.
Justification for classification or non-classification
The weight of evidence data summarized suggests the chemical 1-Methyl-4-hydroxypiperidine to be not likely classified for reproductive toxicity.
Additional information
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