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EC number: 941-924-2 | 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
- Remarks:
- The two substances share structural similarities with common functional groups, esters, and side chains varying in their length. Moreover, the side chains are chemically simple structures which are closely related to substances of known low toxicity.
- Adequacy of study:
- key study
- Study period:
- 2004
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions; few details on test substance given, no analysis of the test compound
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 004
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- few details on test substance given, no analysis of the test compound
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate
- EC Number:
- 234-392-1
- EC Name:
- Decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate
- Cas Number:
- 11138-60-6
- IUPAC Name:
- 2,2-bis[(octanoyloxy)methyl]butyl decanoate
- Reference substance name:
- Trimethylolpropane caprylate caprate
- IUPAC Name:
- Trimethylolpropane caprylate caprate
- Test material form:
- solid - liquid: suspension
- Details on test material:
- TMPCC (ExxonMobil, Lot No. 2, batch no. BL2027) was stored at room temperature.
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Kingston, NY
- Age at study initiation: young adult
- Weight at study initiation: Mean of the maternal body weight: 226 g (Vehicle), 225 g (200 mg/kg bw/day), 227 g (600 mg/kg bw/day), 226 g (2000 mg/kg bw/day)
- Fasting period before study: No
- Housing: Virgin females were cohabitated with singly-housed male rats, one male per female rat for a maximum of 5 days and returned to individual housing in stainless steel wire-bottomed cages after mating.
- Diet: Certified Rodent Diet No. 5002 (PMI Feeds Inc. St.Louis, MO), ad libitum
- Water: water passaged through a reverse osmosis membrane with chlorine added as a bacteriostat, ad libitum
- Acclimation period: yes, period not mentioned
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- dermal
- Vehicle:
- corn oil
- Details on exposure:
- - Doses: 0, 200, 600, and 2,000 mg/kg/day.
- Dose formulation: 0 (vehicle only), 100, 300, and 1,000mg/mL
- Dosage volume: 2 mL/kg.
- Application of dose: The dosage amount was applied directly to the clipped area on the dorsum of the rat at approximately the same time each day and spread uniformly over the area with a glass rod. The skin application site was occluded during treatment with a gauze pad secured with Vetrapt or Micropores tape to prevent oral ingestion and to minimize loss of material from under the patch. - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Treatment on Gestation Days (GD) 6 - 15
- Frequency of treatment:
- daily
- Duration of test:
- Termination of the study by CO2 inhalation on GD 20.
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
200
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
600
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
2000
Basis:
nominal conc.
- No. of animals per sex per dose:
- 25 females per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose dependent occurrence of skin irritation. Higher levels than 2000 mg/kg bw/day might be expected to produce marked irritation thereby compromising the interpretaion of developmental results.
- Rationale for animal assignment (if not random): Computer-generated randomization by weight (Barlett´s test for homogeneity) such that the groups were not statistically different (5% significance level) from each other.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS
- Time schedule: Animals were checked for mortality twice daily during the treatment period and daily thereafter.
DETAILED CLINICAL OBSERVATIONS
- Time schedule: Animals were checked for signs of reaction to treatment and/or symptoms of illness once daily before treatment, approx. 60 min after treatment during the dosing period. The dosing site was examined daily prior to substance application for signs of skin irritation according to Draize.
BODY WEIGHT
- Time schedule for examinations: Recorded on GD 0 and daily during the treatment period.
FOOD CONSUMPTION AND COMPOUND INTAKE
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg b.w./day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
POST-MORTEM EXAMINATIONS
- Sacrifice on gestation day # 20
- Organs examined: The uterus, uterine contents, position of the fetuses in the uterus and number of corpora lutea. Number and distribution of intrauterine implantations were classified as live or death fetuses, late intrauterine deaths (resorptions) and early intrauterine resorption sites. Live fetuses were sexed and further examined (see below). - Ovaries and uterine content:
- - Gravid uterus weight
- Number of corpora lutea
- Number of implantations
- Number of early resorptions
- Number of late resorptions - Fetal examinations:
- - External examinations: all per litter
- Soft tissue examinations: half per litter
- Skeletal examinations: half per litter
- Head examinations: half per litter (the heads of the animals used for soft tissue examinations) - Statistics:
- Clinical observation and other proportion data were analyzed using the Variance Test for Homogeneity of the Binomial Distribution (Snedecor and Cochran, 1967). Quantitative continuous data (e.g., maternal body weights, body weight changes, feed consumption values, litter averages for percent male fetuses, percent resorbed conceptuses, fetal body weights, fetal anomaly data, and fetal ossification data) were analyzed using Bartlett’s Test
for Homogeneity of Variance (Sokal and Rohlf, 1969) and the Analysis of Variance (Snedecor and Cochran, 1967) when Bartlett’s Test was not significant (p40.05). If the Analysis of Variance was significant (pr0.05), Dunnett’s Test (Dunnett, 1955) was used to identify the statistical significance of the individual groups. If the Analysis of Variance was not appropriate, i.e., Bartlett’s Test was significant (pr0.05), the Kruskal-Wallis Test (Sokal and Rohlf, 1969) was used when < 75% ties were present. In cases where the Kruskal-Wallis Test was statistically significant (p<0.05), Dunn’s Method of Multiple Comparisons (Dunn, 1964) was used to identify the statistical significance of the individual groups. If there were 475% tied, Fisher’s Exact Test (Siegel, 1956) was used to analyze the data. Count data obtained at Caesarian-sectioning of the dams were evaluated using the procedures described above for the Kruskal-Wallis Test.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes. Remark: local irritation
Details on maternal toxic effects:
The two highest dose levels caused some local irritation at the site of application, but no decreases in maternal weight gain or feed consumption. Two animals in the control group and one animal in the high-dose group died within 6 h after first application; these were not considered to be treatment related and the animals were replaced. One dam of the mid-dose goup (1/25) having a litter consisting of seven early resorptions was pointed out as single non-dosage dependent event and to be within the ranges observed historically at the test facility.
Necropsy findings were limited to skin flaking and scabbing first identified in life and observations related to wearing the Elizabethan collar (local alopecia, chromorhinorrhea, and neck lesions).
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- > 2 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Remarks:
- local
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Remarks:
- systemic
- Effect level:
- 2 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
There were no significant differences from control in any of the developmental parameters measured, including embryo/fetal viability, fetal weight, malformations, or variations. The observed effects in fetuses were dose-independent and regarded to be sporadic.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- > 2 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- fetal/pup body weight changes
- changes in litter size and weights
- external malformations
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1: Skin reaction observations
|
0 mg/kg bw/d |
200 mg/kg bw/d |
600 mg/kg bw/d |
2000 mg/kg bw/d |
Maximum possible incidencesa |
375/25 |
375/25 |
375/25 |
375/25 |
Erythema |
||||
Total |
0/0 |
2/1 |
22/4 |
91/13b |
Grade 1 |
0/0 |
2/1 |
10/4 |
81/13b |
Grade 2 |
0/0 |
0/0 |
4/1 |
10/4b |
Flaking |
||||
Total |
11/3 |
15/2 |
55/6 |
170/17b |
Grade 1 |
11/3 |
9/2 |
27/5 |
61/14b |
Grade 2 |
0/0 |
6/1 |
19/4 |
71/14b |
Grade 3 |
0/0 |
0/0 |
9/1 |
38/7 b |
Edema |
||||
Total |
0/0 |
0/0 |
23/4 |
83/11b |
Grade 1 |
0/0 |
0/0 |
18/4 |
59/11b |
Grade 2 |
0/0 |
0/0 |
5/1 |
24/6b |
Scab |
0/0 |
0/0 |
6/2 |
19/4 |
a: Maximum incidence : Days x rats from first treatment on GD 6 through sacrifice on GD 20 divided by the number of rats examined per group on GD 6-20
b: Significantly different from vehicle control group value (p≤0.01)
Table 2: Maternal reproductive, litter, and fetal alteration observations: Caesarian-Section results on GD 20
|
0 mg/kg bw/d |
200 mg/kg bw/d |
600 mg/kg bw/d |
2000 mg/kg bw/d |
Rats pregnant and sectioned on Day 20 of gestation (n) |
25 |
23 |
22b |
24 |
Corpora lutea/dam |
16.4 |
16.6 |
16.9 |
16.5 |
Implantation sites/litter |
15.0 |
15.4 |
14.9 |
14.2 |
Litter size |
||||
Live fetuses/litter |
14.6 |
14.6 |
14.0 |
13.3 |
Live fetuses (n) |
364 |
335 |
308 |
320 |
Dead fetuses (n) |
0 |
0 |
0 |
0 |
Resorptions |
0.4 |
0.9 |
0.9 |
0.9 |
Early (n) |
10 |
20 |
19 |
21 |
Late (n) |
1 |
0 |
0 |
0 |
Dams with any resorptions n(%) |
9 (36) |
11 (48) |
15 (68) |
11 (46) |
% resorbed/litter |
2.9 |
5.4 |
5.8 |
5.0 |
% male/litter |
51.3 |
50.8 |
48.1 |
47.7 |
Live fetal body weight (g/litter) |
3.68 |
3.62 |
3.69 |
3.75 |
Male |
3.77 |
3.68 |
3.82 |
3.85 |
Female |
3.58 |
3.56 |
3.58 |
3.65 |
Fetuses evaluated (n) |
364 |
335 |
308 |
320 |
Litters with any alterations observed n(%) |
10 (40) |
8 (35) |
14 (64) |
7 (25) |
Fetuses with any alterations observed n(%) |
13 (3.5) |
10 (3.0) |
20 (6.5) |
9 (2.0) |
% fetuses/litter with any alterations observed |
3.5 |
2.9 |
6.8c |
2.7 |
b: Excludes values for one dam, which had a litter consisting of seven early resorptions.
c: Significantly different from vehicle control group value (p≤0.05)
Table 3: Fetal evaluations
|
0 mg/kg bw/d |
200 mg/kg bw/d |
600 mg/kg bw/d |
2000 mg/kg bw/d |
Litters evaluated |
25 |
23 |
22b |
24 |
Fetuses evaluated |
364 |
335 |
308 |
320 |
Live |
364 |
335 |
308 |
320 |
Fetal gross external alterations |
364 |
335 |
308 |
320 |
Tail: kinked |
||||
Litter incidence, n (%) |
0(0) |
1 (4.3) |
0(0) |
0(0) |
Fetal incidence, n (%) |
0(0) |
1(0.3) |
0(0) |
0(0) |
Body: hematoma |
||||
Litter incidence, n (%) |
1(4.0) |
0(0) |
0(0) |
0(0) |
Fetal incidence, n (%) |
1 (0.3) |
0(0) |
0(0) |
0(0) |
Fetal soft tissue alterations, evaluations |
174 |
162 |
149 |
155 |
Vessels: umbilical artery descended to the left of urinary bladder |
||||
Litter incidence, n (%) |
2(8.0) |
3(13.0) |
2(9.1) |
2(8.3) |
Fetal incidence, n (%) |
2(1.1) |
3(1.8) |
3(2.0) |
2(1.3) |
Vessels: apparent additional umbilical artery descended left of the bladder |
||||
Litter incidence, n (%) |
0(0) |
0(0) |
1(4.5) |
0(0) |
Fetal incidence, n (%) |
0(0) |
0(0) |
1(0.7) |
0(0) |
Fetal skeletal alterations, evaluations |
190 |
173 |
159 |
165 |
Cervical vertebrae: cervical rib present at 7th cervical vertebrae |
||||
Litter incidence, n (%) |
2(8.0) |
1(4.3) |
1(4.8) |
0(0) |
Fetal incidence, n (%) |
2(1.0) |
2(1.2) |
1(1.2) |
0(0) |
Thoracic vertebrae: centrum, bifid |
||||
Litter incidence, n (%) |
1(4.0) |
1(4.3) |
5(22.7) |
0(0) |
Fetal incidence, n (%) |
1(0.5) |
1(0.6) |
5(3.1)a |
0(0) |
Lumbar vertebrae: centrum, bifid |
||||
Litter incidence, n (%) |
0(0) |
1(4.3) |
0(0) |
0(0) |
Fetal incidence, n (%) |
0(0) |
1(0.6) |
0(0) |
0(0) |
Ribs: wavy |
||||
Litter incidence, n (%) |
0(0) |
0(0) |
2(9.1) |
1(4.2) |
Fetal incidence, n (%) |
0(0) |
0(0) |
2(1.2) |
1(0.5 |
Sternal centra: 1st, not ossified |
||||
Litter incidence, n (%) |
1(4.0) |
0(0) |
0(0) |
2(8.3) |
Fetal incidence, n (%) |
1(0.5) |
0(0) |
0(0) |
2(1.3) |
Sternal centra: 1st, incompletely ossified |
||||
Litter incidence, n (%) |
3(12.0) |
3(13.0) |
2(5.1) |
1(4.2) |
Fetal incidence, n (%) |
4(2.1) |
4(2.3) |
2(1.2) |
1(0.6) |
Pelvis: pubis, incompletely ossified |
||||
Litter incidence, n (%) |
3(12.0) |
0(0) |
4(18.2) |
3(12.5) |
Fetal incidence, n (%) |
3(1.6) |
0(0) |
5(3.1) |
3(1.8) |
Pelvis: ischium, incompletely ossified |
||||
Litter incidence, n (%) |
0(0) |
0(0) |
2(9.1) |
0(0) |
Fetal incidence, n (%) |
0(0) |
0(0) |
2(1.2) |
0(0) |
a: Significantly different from vehicle control group (p≤0.01)
Applicant's summary and conclusion
- Conclusions:
- TMPCC did not cause any developmental toxicity in the Sprague-Dawley rat at dermal dosages up to 2,000 mg/kg/day.
- Executive summary:
The developmental toxicity potential of trimethylolpropane caprylate caprate (TMPCC, CAS no. 11138-60-6) was evaluated in rats. Sprague-Dawley rats were administered TMPCC in a corn oil suspension dermally at dose levels of 0, 200, 600, or 2,000 mg/kg/day on gestation days (GD) 6–15 (sperm positive day5GD 0). Caesarean sections were performed on GD 20 and fetuses were evaluated for viability, growth, and external, visceral, and skeletal abnormalities. Each group consisted of 25 females, with at least 22 per group being pregnant. The two highest dose levels caused some local irritation at the site of application, but no decreases in maternal weight gain. There were no differences from control in any of the developmental parameters measured, including embryo/fetal viability, fetal weight, malformations, or variations. TMPCC did not cause any developmental toxicity in the Sprague-Dawley rat at dermal dosages up to 2,000 mg/kg/day.
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