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EC number: - | CAS number: -
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From June 19, 1979 to June 12, 1980
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 979
- Report date:
- 1979
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 980
- Report date:
- 1980
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- No macroscopic or microscopic examination of sacrificed dams
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- N,N,N-trimethyl-C12-14 (even numbered)-alkyl-1-aminium chloride
- Molecular formula:
- C15H34Cl1N1 (representative molecular formula of C12 chain)
- IUPAC Name:
- N,N,N-trimethyl-C12-14 (even numbered)-alkyl-1-aminium chloride
- Reference substance name:
- Alcohols, C14-15, ethoxylated
- EC Number:
- 614-831-7
- Cas Number:
- 68951-67-7
- IUPAC Name:
- Alcohols, C14-15, ethoxylated
- Test material form:
- other: White-cream, glossy paste
Constituent 1
Constituent 2
- Specific details on test material used for the study:
- Test substance: C12-14 TMAC
Purity: 35% C12-14 TMAC in C14-15 Pareth-7
Appreance: White cream, glossy paste
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Animal supplier source: Accredited breeder - Oury, Domaine De la Chesnaie, 45230 Chatilloon-Coligny
Body weight: 2.7 to 2.9 kg
Sex: Female
Pre-trail period: The animal were maintained under conditions as close as possible to those of the trial for one month pre-trial and were vaccinated against myxomatosis on May 12, 1979. The male rabbits used for mating were supplied from the same breeder and placed under the same experimental conditions as the females
Housing: Animals were placed in individual caging (70×50×30 cm) with plastic perforated floor
Temperature: 21ºC ± 10ºC
Relative humidity: 50 ± 10%
Air changes: 10 times/hour
Allocation to the groups: 13 animals each were grouped to control, test group 1, test group 2 and test group 3.
Tap water: ad libitum
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- The first mating started on September 04, 1979.
- Duration of treatment / exposure:
- The day of mating was considered as day 0 and the animals were dosed daily from day 6 to day 18 inclusive (for 13 consecutive days).
- Frequency of treatment:
- once a day
- Duration of test:
- 28 d
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 mg/kg bw/day
- Remarks:
- 0.35 mg a.i./kg bw/day
- Dose / conc.:
- 8 mg/kg bw/day
- Remarks:
- 1.4 mg a.i./kg bw/day
- Dose / conc.:
- 24 mg/kg bw/day
- Remarks:
- 8.4 mg a.i./kg bw/day
- No. of animals per sex per dose:
- 13 female rabbits per dose
- Control animals:
- yes
- Details on study design:
- Preliminary study
Animal details: 3 female New Zealand rabbits for each dose group, weighing about 3 kg
Route of administration: Oral by stomach tube
Dose levels (mg/kg bw/day): 25 mg/kg bw/day (Test group 1), 50 mg/kg bw/day (Test group 2), 100 mg/kg bw/day (Test group 3), 200 mg/kg bw/day (Test group 4), 400 mg/kg bw/day (Test group 5)
Test substance was administered as an aqueous solution at following concentration:
Test group 1: 1.25 %
Test group 2: 2.50 %
Test group 3: 5 %
Test group 4: 10 %
Test group 5: 20 %
The solution were prepared every 3rd or 4th d and stored at 4ºC. 2 mL/kg bw was administered for each group. The preliminary test results obtained indicated that the test substance was toxic at the dose levels of 100, 200 and 400 mg/kg bw/day by oral route. 50 mg/kg did seem to be the threshold of an indirect embryotoxic action.
Main study
Based on preliminary testing results, following dose levels were selected for main study:
Test group 1: 1 mg/kg bw/day
Test group 2: 5 mg/kg bw/day
Test group 3: 25 mg/kg bw/day
Examinations
- Maternal examinations:
- - Behaviour and clinical symptoms: daily
- Body weight: every 3 days during pregnancy
- Food consumption: daily
- Number of corpora lutea, implantations, resorptions - Ovaries and uterine content:
- Staining of implantation sites with ammonium sulphide
- Number of corpora lutea
- Number of implantations
- Number of absorptions - Fetal examinations:
- - Number of viable and dead foetuses
- Macroscopic external observations
- Individual weights
- Sex
- 2/3 of foetuses stained with alizarin for skeletal examination
- 1/3 of foetuses immersed on Bouin: sections cut for examination of visceral abnormalities (method adapted from Wilson technique)
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No difference of growth curve of treated groups compared to controls was observed.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No difference of growth curve of treated groups compared to controls was observed.
- 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
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- No mortality, no difference of growth curve of treated groups compared to controls, no difference in food consumption.
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- The rate of resorptions was considered low and comparable in all groups.
- Dead fetuses:
- no effects observed
- Details on maternal toxic effects:
- There was a higher number of non-pregnant females in group I. The rate of resorptions is considered low, and comparable in all groups. No histopathology was performed on the sacrificed dams end of term.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 24 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: No effects were observed at highest test dose
- Remarks on result:
- other:
- Remarks:
- NOAEL 8.4 mg a.i./kg bw/day
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- External malformations:
- no effects observed
- Description (incidence and severity):
- In the high dose group, one foetus showed a torsion of the fore limbs. No other external abnormality was observed in any of the dose groups.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- Incidence in treated groups were comparable to controls.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- - Dilated and haemorrhagic cerebral ventricles in one foetus of control group
- Left hydro-ureter in one foetus of low dose group
- Retinal folds in region of optic nerve in 13 foetuses: Control: 3 (11%); low dose: 2 (9%); mid dose: 4 (14%); and high dose: 4 (16%). These were considered to be caused by fixation artefact. - Details on embryotoxic / teratogenic effects:
- No foetal mortality was observed.
External abnormalities:
In the high dose group, one foetus showed a torsion of the fore limbs. No other external abnormality was observed in any of the dose groups.
Visceral abnormalities:
- dilated and haemorrhagic cerebral ventricles in one foetus of control group
- left hydro-ureter in one foetus of low dose group.
- retinal folds in region of optic nerve in 13 foetuses: Control: 3 (11%); low dose: 2 (9%); mid dose: 4 (14%); and high dose: 4 (16%). These were considered to be caused by fixation artefact.
Skeletal abnormalities: See table: Incidence in treated groups are comparable to controls.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 24 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effects were observed at highest test dose
- Remarks on result:
- other: NOAEL: 8.4 mg a.i./kgbw/day
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Any other information on results incl. tables
Maternal toxic Effects
Preliminary study
25, 50, 100, 200, and 400 mg test material /kg bw/day using 3 animals per dose group.
Mortality
Dose of test substance (mg/kg bw/day) |
25 |
50 |
100 |
200 |
400 |
mortality |
1/3 |
1/3 |
2/3 (day 18,26) |
3/3 (all day 10) |
3/3 (all day 7) |
At 50 and 100 mg groups, a clear fall in body weight was observed between days 12 and 18. At 25 mg, two of the three females showed anorexia. From first day of treatment food consumption was clearly decreased at 50 and 100 mg/kg.
Final study
No mortality, no difference of growth curve of treated groups compared to controls, no difference in food consumption. There was a higher number of non-pregnant females in group I. The rate of resorptions is considered low, and comparable in all groups. No histopathology was performed on the sacrificed dams end of term.
Teratogenic/embryotoxic effects
Preliminary study on 25, 50, 100, 200, and 400 mg test material/kg bw/day using 3 animals per dose group. At 50 mg, the two females showed resorption sites. The weight of foetuses of the 50 mg group were low. Macroscopic examination, number and mean weight of foetuses of the 25 mg group showed no embryotoxic effect. 50 mg/kg/day seems to be the threshold for an indirect embryotoxic action.
Final study
No
foetal mortality was observed.
External abnormalities
In the high dose group, one foetus showed a torsion of the fore
limbs. No other external abnormality was observed in any of the dose
groups.
Visceral abnormalities
- Dilated and haemorrhagic cerebral ventricles in one foetus of control group
- left hydro-ureter in one foetus of low dose group.
-
Retinal folds in region of optic nerve in 13 foetuses: Control: 3 (11%);
low dose: 2 (9%); mid dose: 4 (14%); and high dose: 4 (16%). These were
considered to be caused by fixation artefact.
Skeletal
abnormalities: Incidence in treated groups are comparable to controls.
Table for Maternal effects (separate data for all dosage groups)
Maternal effects |
||||||
Parameter |
control data |
low dose |
medium dose |
high dose |
dose-response |
|
historical |
study |
|||||
Number of dams examined |
|
13 |
14 |
13 |
13 |
|
Clinical findings during application of test substance |
|
no |
no |
no |
no |
|
Mortality of dams state % |
|
0 |
0 |
0 |
0 |
|
Abortions |
|
0 |
0 |
0 |
0 |
|
Body weight (day 28) g gain day 0-28 (end of test) g, |
|
3468 |
3313 |
3450 |
3369 |
- |
Food consumption (g/day/dam) |
|
|
|
|
|
- |
Water consumption if test substance is applied with drinking water |
|
not recorded |
not recorded |
not recorded |
not recorded |
|
Pregnancies pregnancy rate or % |
|
11 |
8 |
11 |
13 |
+/- |
Necropsy findings in dams dead before end of test |
|
none died |
none died |
none died |
none died |
|
Table for developmental effects (separate data for all dosage groups)
Litter response (Caesarean section data) |
||||||
Parameter |
control data |
low dose |
medium dose |
high dose |
dose-response |
|
historical |
study |
|||||
Number full-term pregnant females |
|
11 |
8 |
11 |
13 |
+/- |
Corpora lutea number per pregnant female |
|
98 |
73 |
97 |
104 |
+/- |
Implantations number per pregnant female |
|
84 |
71 |
85 |
98 |
- |
Resorptions number per pregnant female |
|
1 |
4 |
2 |
7 |
- |
total number of foetuses |
|
83 |
67 |
83 |
91 |
+/- |
pre-implantation loss state % |
|
14% |
3% |
12% |
6% |
- |
post-implantation loss state % |
|
1% |
6% |
2% |
7% |
- |
total number of litters |
|
11 |
8 |
11 |
13 |
+/- |
fetuses / litter |
|
7.55 |
8.37 |
7.55 |
7.00 |
+/- |
live fetuses / litter state ratio |
|
7.55 |
8.37 |
7.55 |
7.00 |
+/- |
dead fetuses / litter state ratio |
|
0 |
0 |
0 |
0 |
|
fetus weight (mean) [g] |
|
33.63 |
31.73 |
34.21 |
35.17 |
+/- |
placenta weight (mean) [g] |
|
not recorded |
not recorded |
not recorded |
not recorded |
|
crown-rump length (mean) [mm] |
|
not recorded |
not recorded |
not recorded |
not recorded |
|
Fetal sex ratio [state ratio m/f] |
|
40/38 |
26/34 |
39/39 |
48/34 |
+/- |
Table for developmental effects (separate data for all dosage groups)
Examination of the foetuses |
||||||
Parameter |
control data |
low dose |
medium dose |
high dose |
dose-response |
|
historical |
study |
|||||
External abnormalities [%] |
|
1 |
0 |
0 |
0 |
- |
Skeletal abnormal ossifications |
|
|
|
|
|
- |
incomplete ossifications sternebrae [%] |
|
32 |
29 |
30 |
36 |
- |
incomplete ossifications skull [%] |
|
23 |
9 |
11 |
15 |
- |
missing ossifications sternebrae [%] |
|
14 |
11 |
12 |
21 |
|
abnormal ossifications |
|
1 |
|
1 |
|
- |
Visceral abnormalities [%] |
|
1 |
1 |
0 |
0 |
- |
Applicant's summary and conclusion
- Conclusions:
- Under study conditions, the NOAEL of test substance for maternal and embryotoxic effects/teratogenicty was determined to be 24 mg/kg bw/day (i.e., equivalent to 8.4 mg a.i./kg bw/day)
- Executive summary:
A study was conducted to determine the teratogenicity of test substance, C12-14 TMAC (active ingredient 35%), according to the method comparable to OECD 414. During gestation Days 6 -18, four groups of 13 female New Zealand White rabbits were dosed by stomach tube at dose levels of 0, 2, 8 and 24 mg/kg bw/day of test substance (35% C12 -14 -TMAC in dobanol 45E7 (i.e., C14 -15 AE7)), in 2 mL/kg bw/day daily prepared solutions in water. Animals were sacrificed on Day 29. Examinations included daily observations of behaviour and clinical symptoms, daily food consumption, and body weight every three days. Upon sacrifice, number of corpora lutea, implantations and resorptions were examined. For foetuses, number of viable and dead, macroscopic external examinations, sex, individual weights, skeletal examinations (2/3), and visceral abnormalities (1/3) were conducted. A preliminary study was undertaken under similar conditions, applying 5 dose groups: 0, 25, 50, 100, 200 and 400 mg/kg bw/day using three animals per dose group. At 50 mg, the two females showed resorption sites. The weight of foetuses of the 50 mg group were low. Macroscopic examination, number and mean weight of foetuses of the 25 mg group showed no embryotoxic effect. 50 mg/kg/day did seem to be the threshold for an indirect embryotoxic action. In the final study, no signs of maternal toxicity was observed. Also no foetal mortality was observed. Numbers of corpora lutea and resorptions were comparable. The number of pregnancies at the low dose group did seem to be diminished, but this was considered an incidental observation. There was no change in frequency of external, visceral and skeletal observations. No maternal toxic or embryotoxic/teratogenic effects were seen up to hightest tested dose of 24 mg/kg bw/day (i.e., equivalent to 8.4 mg a.i./kg bw/day). Under study conditions, the NOAEL of test substance for maternal and embryotoxic effects/teratogenicty in rabbits was determined to be 24 mg/kg bw/day (i.e., equivalent to 8.4 mg a.i./kg bw/day) (Fave 1980).
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