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EC number: 258-132-1 | CAS number: 52722-86-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 998
- Reference Type:
- secondary source
- Title:
- SIDS DOSSIER: 2,2,6,6-Tetramethylpiperidin-4-ol, CAS-No: 2403-88-5
- Author:
- OECD SIDS
- Year:
- 2 002
- Bibliographic source:
- OECD SIDS
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Remarks:
- Biosafety Research Center, Food, Drugs and Pesticides (An-Pyo Center), Japan
- Limit test:
- no
Test material
- Reference substance name:
- 2,2,6,6-tetramethylpiperidin-4-ol
- EC Number:
- 219-291-2
- EC Name:
- 2,2,6,6-tetramethylpiperidin-4-ol
- Cas Number:
- 2403-88-5
- IUPAC Name:
- 2,2,6,6-tetramethylpiperidin-4-ol
- Details on test material:
- - Name of test material (as cited in study report): 2,2,6,6-Tetramethylpiperidin-4-ol
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 10 weeks old for female and male animals
- Weight at study initiation: 359 - 400g for males; 227 - 282g for females
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: at most 3 days, until proof of pregnancy
- Proof of pregnancy: vaginal plug or sperm in vaginal smear - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- Male: for 48 days from 2 weeks prior to mating
Female: for 41-52 days from 2 weeks prior to mating to day 3 postpartum throughout mating and pregnancy - Frequency of treatment:
- once daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 60, 200, 600
Basis:
actual ingested
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once a day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once a day
BODY WEIGHT: Yes
- Time schedule for examinations: for males: once a week, the first and the last day of the administration, the sacrificed day; for pregnant females: on day 0, 14 and 20 of gestation, on day 0 and 4 of lactation
FOOD CONSUMPTION: Yes
- Time schedule: once a week, on the same day when body wt. determined - Oestrous cyclicity (parental animals):
- estrus cycle assessed during study
- Sperm parameters (parental animals):
- Parameters examined in P male parental generations:
testis weight, epididymis weight - Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); excess pups were killed and discarded
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead.
OTHER: General appearance once a day - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals after 49 days
- Maternal animals: All surviving animals after the last litter of each generation was weaned
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGHTS
Organ weights (brain, thymid gland, liver, kidney, spleen, adrenal, thymus and for males, testes and epididymis. Dead animals in 60 and 600 mg/kg group, and the parent from which all pups died in 600 mg/kg group : brain, spinal cord, pituitary gland, eyeball, harderian gland, salivary gland, tongue, thyroid gland (including parathyroid gland), thymus, heart, trachea, bronchus, esophagus, lung, liver, kidney, adrenal, spleen, stomach, duodenum, small intestine, large intestine, pancreas, urinary bladder, sternum, bone marrow, sciatic nerve, lymph node, testes, epididymis, prostate, seminal vesicle, ovary, uterus, vagina, mammary gland, skin. All pregnant males and females in 60 and 200 mg/kg group: kidney and any organs which might be expected to have histopathological changes at the higher doses. - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring were sacrificed at #4 days of age.
- These animals were subjected to postmortem examinations (macroscopic examination) as follows: Full macroscopic examination on all of pups
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. - Statistics:
- Dunnett's or Scheffe's test for continuous data and Chi square test for quantal data
- Reproductive indices:
- copulation index (No. of pairs with successful copulation/No. of pairs mated x 100), fertility index (No. of pregnant animals/No. of pairs with successful copulation x 100), implantation index (No. of implantation sites/No. of corpora lutea x 100), gestation index (No. of females wilth live pups/No. of living pregnant females x 100), delivery index (No. of pups born/No. of implantation sites x 100)
- Offspring viability indices:
- live birth index (No. of live pups on day 0/No. ofpups born x 100), viability index (No. of live pups on day 4/No. of live pups on day 0 x 100)
Results and discussion
Results: P0 (first parental generation)
Details on results (P0)
Deaths caused by the test substance were observed one female (on day 16) of the 60 mg/kg group, and three males (on day 6 - 9) and one female (on day 3) of the 600 mg/kg group.
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS):
Low body weight gain during the premating period in females at 200 mg/kg was observed (Dunnets test p < 0.05).
Food/water consumption: For males, a tendency for increase in food consumption during administration period was observed at 600 mg/kg, and statistical significant difference from controls was noticed on day 8 to 48 of the administration. For females, statistical significant difference from controls was observed during premating period (on day 8- 15) and gestation period (on day 7 - 14), respectively.
REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS):
Estrous cycle examination: continuous diestrus was observed in three females of the 600 mg/kg group and the mean estrous cycle of this group showed extension compared with the control group (p < 0.05).
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS):
No statistical significant difference from controls.
GROSS PATHOLOGY (PARENTAL ANIMALS): No statistically significant effects were observed in all groups.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- > 600 mg/kg bw/day (actual dose received)
- Sex:
- male
- Basis for effect level:
- other: no effects at the highest dose (600mg/kg)
- Dose descriptor:
- NOEL
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: other: estrus cycle increased significantly in the 600mg/kg group
Results: F1 generation
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: pups of the 600mg/kg group showed lower body weight on day 4 of lactation
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Reproduction results of rats treated orally with 2,2,6,6 -Tetramethylpiperidin-4 -ol:
Dose level (mg/kg/day) | 0 | 60 | 200 | 600 |
No. of pairs mated | 12 | 11 | 12 | 10 |
No. of pairs mated with successful copulation | 12 | 11 | 12 | 10 |
Copulation index (%) | 100 | 100 | 100 | 90.9 |
No. of pregnant females | 12 | 11 | 12 | 10 |
Fertility index (%) | 100 | 100 | 100 | 100 |
Pairing days until copulation (mean ± S.D.) | 2.9±1.1 | 2.3±0.9 | 2.4±0.7 | 3.1±0.8 |
No. of corpora lutea (mean ± S.D.) | 18.8±1.5 | 20.6±2.9 | 19.6±2.5 | 18.6±1.7 |
No. of implantation sites (mean ± S.D.) | 17.6±1.6 | 17.2±3.3 | 18.2±1.9 | 17.0±2.3 |
Implantation index (%, Mean ± S.D.) | 93.4±5.4 | 83.5±14.3 | 93.2±7.5 | 91.3±8.0 |
No. of pregnant females with parturition (mean ± S.D.) | 12 | 11 | 12 | 10 |
Gestation length (days, mean ± S.D.) | 22.7±0.5 | 22.3±0.5 | 22.6±0.5 | 22.4±0.5 |
Gestation index (%) | 100 | 100 | 100 | 100 |
Estrus cycle (days, mean ± S.D.) | 4.1±0.3 | 4.1±0.3 | 4.3±0.5 | 4.5±0.4? |
Copulation index (%) = (No. of pairs with successful copulation / No. of pairs mated) x 100
Fertility index (%) = (No. of pregnant females / No. of pairs with successful copulation) x 100
Gestation index (%) = (No. of females with live pups / No. ofpregnant females) x 100
Significant difference from control group
? = P<0.05
Litter results of rats treated orally with 2,2,6,6 -Tetramethylpiperidin-4 -ol:
Dose level (mg/kg/day) | 0 | 60 | 200 | 600 |
No. of pups born | 16.3±2.0 | 15.3±3.3 | 15.4±1.5 | 15.7±2.7 |
Delivery index (%) | 92.9±7.0 | 90.3±16.2 | 85.2±6.9 | 92.1±6.0 |
No. of pups alive on day 0 of lactation | ||||
Total | 16.3±2.0 | 15.2±3.3 | 15.3±1.4 | 15.7±2.7 |
Male | 8.2±2.2 | 7.7±2.3 | 7.9±1.8 | 7.0±3.0 |
Female | 8.2±1.5 | 7.5±2.6 | 7.4±2.2 | 8.7±2.3 |
Live birth index (%) | 100±0.0 | 99.5±1.8 | 99.5±1.7 | 100±0.0 |
Sex ratio (Male/Female) | 1.05±0.37 | 1.15±0.46 | 1.22±0.60 | 0.90±0.57 |
No. of pups alive on day 4 of lactation | ||||
Total | ||||
Male | 7.8±2.0 | 7.5±2.2 | 6.5±2.7 | 4.3±2.9 |
Female | 7.4±1.1 | 6.5±2.5 | 6.3±2.5 | 6.4±3.7 |
Viability index (%) | ||||
Total | 96.1±7.5 | 96.8±5.4 | 82.7±28.4 | 67.2±39.2 |
Male | 91.9±9.9 | 86.2±10.4 | 85.8±20.3 | 70.7±35.0 |
No. of total dead pups born (mean±S.D.) | 0.0±0.0 | 0.1±0.3 | 0.1±0.3 | 0.0±0.0 |
Stillbirth | 0.0±0.0 | 0.0±0.0 | 0.0±0.0 | 0.0±0.0 |
cannibalism | 0.0±0.0 | 0.1±0.3 | 0.1±0.3 | 0.0±0.0 |
Delivery index (%) = (No. of pups born/No. of implantation sites) x 100
Live birth index (%) = (No. of live pups on day 0/No. of pups born) x 100
Viability index (%) = (No. of live pups on day 4/No. of live pups on day 0) x 100
Sex ratio = Total No. of male pups/ Total No. of female pups
Values are expressed as Mean±S.D. except sex ratio
Applicant's summary and conclusion
- Conclusions:
- On the basis of these findings, NOEL of 2,2,6,6-Tetramethyl-4-hydroxypiperidine for reproductive toxicity to parental rats were considered to be more than 600 mg/kg/day for males, and 200 mg/kg/day for females. Moreover, NOEL of the test substance to F1 offspring was established to be 200 mg/kg/day.
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