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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
Reference
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
Reference:
Composition 0
Qualifier:
according to
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
Test material information:
Composition 1
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
Estrous 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
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: estrous 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: estrous 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

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

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.

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.