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EC number: 215-664-9 | CAS number: 1338-41-6
- 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:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
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)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Docosanoic acid
- EC Number:
- 204-010-8
- EC Name:
- Docosanoic acid
- Cas Number:
- 112-85-6
- Molecular formula:
- C22H44O2
- IUPAC Name:
- docosanoic acid
- Details on test material:
- - Name of test material (as cited in study report): docosanoic acid
- Physical state: white powder
- Analytical purity: 85.9 %
- Lot/batch No.: 60805X
- Impurities (identity and concentrations): C14-C20 fatty acids: 10.9 %, C24 fatty acids: 2.3 %
- Storage condition of test material: at room temperature in the dark
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan, Hino, Tokyo
- Age at study initiation: 8 weeks
- Weight at study initiation: male: 312.1 - 363.7 g; female: 205.3 - 230.8 g
- Housing: metal wire floor cages
- Diet (ad libitum): CE-2, CLEA Japan
- Water (ad libitum): tap water
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 1
- Humidity (%): 50 - 65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: prepared more frequently than once a week; aliquots were kept refrigerated in airtight conditions at each concentration
VEHICLE
- Justification for use and choice of vehicle (if other than water): insolubility in water
- Amount of vehicle (if gavage): 5 mL/kg bw
- Lot/batch no. (if required): V6H2050 - Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: up to 2 weeks
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- Further mating after two unsuccessful attempts: no
- After successful mating each pregnant female was caged (how): individually - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- - males: 42 days
- females: 14 days prior to mating until day 3 of lactation - Frequency of treatment:
- daily
- Details on study schedule:
- - Age at mating of the mated animals in the study: 10 weeks
Doses / concentrations
- Remarks:
- Doses / Concentrations:
100, 300, 1000 mg/kg bw/d
Basis:
actual ingested
- No. of animals per sex per dose:
- 13
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on a preliminary 14 day-repeated dose toxicity study, where no signs of toxicity were found
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once a day
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: males on day 1, 8, 15, 22, 29, 36 and 42; females premating on day 1, 8 and 15; at pregnancy on day 0, 7, 14 and 20; at lactation on day 0 and 4
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
HAEMATOLOGY: Yes (males only)
- Time schedule for collection of blood: prior to autopsy
- Anaesthetic used for blood collection: Yes, pentobarbital sodium
- Animals fasted: 18 - 24 h before sacrifice
- How many animals: all surviving animals
- Parameters checked: red blood cell count (RBC), white blood cell count (WBC), haemoglobin content (Hb), mean corpuscular volume (MCV), ahematocrit (Ht), mean corpuscular haemoglobin content (MCH), mean corpuscular haemoglobin concentration (MCHC)
CLINICAL CHEMISTRY: Yes (males only)
- Animals fasted: 18 - 24 h before sacrifice
- How many animals: all surviving animals
- Parameters checked: total protein, albumin, total cholesterol concentration, glucose, urea nitrogen, creatinine, alkaline phosphatase activity, GOT, GPT, γ-GTP, triglyceride concentration, inorganic phosphorus, total bilirubin, calcium, sodium, potassium, chlorine, A/G ratio
URINALYSIS: No - Sperm parameters (parental animals):
- Parameters examined in all male parental generations: testis and epididymis weight
- Litter observations:
- STANDARDISATION OF LITTERS
not performed
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies
GROSS EXAMINATION OF DEAD PUPS:
yes: external and internal abnormalities; possible cause of death was determined for pups born or found dead - Postmortem examinations (parental animals):
- SACRIFICE
all surviving animals
GROSS PATHOLOGY: Yes
Organ weights:
males: heart, liver, kidneys, thymus, testes, epididymides
females: heart, liver, kidneys, thymus
HISTOPATHOLOGY: Yes (control and 1000 mg/kg bw /day group):
males: heart, liver, spleen, kidney, adrenal, testis, epididymis, brain, thymus, bladder
females: brain, liver, spleen, thymus, kidney, adrenal, bladder, heart, ovary - Postmortem examinations (offspring):
- SACRIFICE
- F1 offspring not selected as parental animals was sacrificed at 4 days of age
- these animals were subjected to postmortem examinations (macroscopic examination) including: external and visceral malformations - Statistics:
- Yates-test, Mann-Whitney-U-test, Fisher exact-test, Bartlett-test, Dunnett-test, Scheffe-test, Kruskal-Wallis-test
- Reproductive indices:
- - copulation index = (number of copulated pairs / number of pairs mated) x 100
- fertility index = (number of pregnant animals / number of copulated pairs) x 100
- gestation index = (number of pregnant females with pups alive / number of pregnant females) x 100
- implantation index = (number of implantation sites / number of corpora lutea) x 100 - Offspring viability indices:
- - delivery index = (number of pups born / number of implantation sites) x 100
- birth index = (number of pups alive on day 0 / number of implantation sites) x 100
- live birth index = (number of pups alive on day 0 / number of pups born) x 100
- sex ratio on day 0 = (number of males pups alive on day 0 / number of female pups alive on day 0) x 100
- viability index = (number of pups alive on day 4 / number of pups alive on day 0) x 100
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 100 mg/kg bw/d dose group: significant increase of body weights of males and significant decrease of female body weights during lactation (non-adverse)
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- 100 mg/kg bw/d dose group: significant increase of body weights of males and significant decrease of female body weights during lactation (non-adverse)
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 1000 mg/kg bw/d: sporadic findings in brain, heart, liver, spleen, kidney, adrenals, thymus and testes in males and females (non-adverse)
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Details on results (P0)
No deaths or abnormalities in general condition were observed in any of the treated groups.
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Body weight gain in male animals of the 100 mg/kg bw/day group was higher when compared to the 300 and 1000 mg/kg bw/day dose groups and to the control group (10-33%) over the whole treatment period. Since this effect showed no dose-relation and no other effects were observed in this dose group, it was regarded as non-adverse.
Food consumption of males of the 100 mg/kg bw dose group was about 4-10% increased when compared to controls. A significant decreased food consumption was observed in females of the same dose group during lactation. Since this effect was not dose-related, it was regarded to be not treatment related.
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
No significant differences in number of corpora lutea, implantation rate, number of implantations and all other reproductive parameters in all treated groups compared to the controls.
ORGAN WEIGHTS
A significant liver weight increase (12% (absolute weight), 5% (relative weight)) in males of the 100 mg/kg bw/day dose group and a signficant decrease in kidney weights in females (8% (absolute weight), 3% (non-adervse)) was observed. As there was no dose relationship and no effects were observed at histopathology, they were regarded as non-adverse.
GROSS PATHOLOGY
In males of the 100 mg/kg bw/dose group, diminishment of thymus (1 animal), accessory spleen (1 animal) and liver changes (yellowish colouring (2 animals), pale spot (1 animal), accentuation of lobular pattern (1 animals)) were observed. In males of the 300 mg/kg bw/dose group, enlargment of thyroid (1 animal), pale lung (1 animal), diminishment of thymus (1 animal) and liver changes ((pale area (2 animals), pale spot (1 animal)) were observed. In males of the 1000 mg/kg bw/dose group, diminishment of thymus (1 animal), small and enlarged thymus (1 animal each), pale lung (1 animal) and yellowish colouring of the liver (2 animals) was observed.
Focal constriction of the spleen was observed in two high-dose group females and adrenal enlargement in one female animal of the 100 mg/kg bw dose group. Since the observed effects in male and female animals were found without any dose-relationship and only in few animals, they were regarded as not tretement related.
HISTOPATHOLOGY: NON-NEOPLASTIC
Mycardial degeneration, liver fatty change, changes in spleen and kidney were found to the same extent in few male animals of the highest dose group as compared to males of the control group. One male animal of the highest dose group showed slight fibrosis of the adrenal gland and another one very slight changes of the testes.
The only change differing from controls in females of the high dose group was a thalamus mineralisation in the brain found in one animal. Thus, the effects were regarded as not treatment related.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Remarks:
- fertility
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no substance-related findings were observed
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Details on results (F1)
No change in the number of birth, birth rate, infant live birth rate, infant survival and birth rates at day 4 was found in all dose groups when compared to controls.
CLINICAL SIGNS (OFFSPRING)
No clincial signs were observed.
BODY WEIGHT (OFFSPRING)
Body weight of pups of the treatment groups differed not from the controls.
GROSS PATHOLOGY (OFFSPRING)
No morphological abnormalities were found in all groups.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Remarks:
- developmental
- Generation:
- F1
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no substance-related findings were observed
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Table 1: Reproductive and offspring indices from dams and pups after oral treatment of parental animals with the test substance in the combined repeated dose and reproductive/developmental screening study (mean ±SD, (N))
Dose group (mg/kg) |
0 |
100 |
300 |
1000 |
Number of pregnant females |
13 |
12 |
12 |
13 |
Number of pregnant females with live pups |
13 |
12 |
12 |
13 |
Gestation index |
100 |
100 |
100 |
100 |
Gestation length in days |
22.2±0.4 (13) |
22.4±0.5 (12) |
22.3±0.5 (12) |
22.2±0.4 (13) |
Number of corpora lutea |
16.6±1.6 (13) |
16.7±1.8 (12) |
16.8±2.3 (12) |
16.2±1.5 (13) |
Number of implantation sites |
16.1±1.5 (13) |
15.8±2.1 (12) |
16.0±1.5 (12) |
15.2±3.1 (13) |
Implantation index |
96.9±5.1 (13) |
94.8±7.1 (12) |
96.1±6.0 (12) |
93.1±15.2 (13) |
Day 0 of lactation |
|
|
|
|
Number of pups born |
15.2±1.6 (13) |
14.8±2.2 (12) |
15.2±1.5 (12) |
14.3±2.7 (13) |
Delivery index |
94.5±8.0 (13) |
93.5±3.9 (12) |
94.9±4.3 (12) |
94.9±6.2 (13) |
Number of live pups |
14.9±1.6 (13) |
14.3±2.2 (12) |
15.1±1.6 (12) |
14.1±2.7 (13) |
Birth index |
93.1±8.8 (13) |
90.7±8.7 (12) |
94.3±5.1 (12) |
93.5±7.2 (13) |
Live birth index |
98.5±2.8 (13) |
97.0±8.5 (12) |
99.4±2.2 (12) |
98.5±4.0 (13) |
Sex ratio on day 0 |
50.0±11.3 (13) |
46.7±9.8 (12) |
54.8±12.3 (12) |
48.9±13.4(13) |
Day 4 of lactation |
|
|
|
|
Number of live pups |
14.7±1.4 (13) |
13.0±4.7 (12) |
15.1±1.6 (12) |
14.1±2.7 (13) |
Viability index |
98.6±2.7 (13) |
89.4±28.8 (12) |
100.0±0.0 (12) |
100.0±0.0 (13) |
Sex ratio on day 4 |
49.8±11.5 (13) |
46.3±10.3 (11) |
54.8±12.3 (12) |
48.9±13.4(13) |
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.