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EC number: 221-618-9 | CAS number: 3164-29-2
- 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
Endpoint summary
Administrative data
Description of key information
Skin sensitation (OECD 429): not sensitizing
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01 - 23 June 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 22 July 2010
- Deviations:
- yes
- Remarks:
- / different/higher acceptable body weight loss than in TG (10 instead of 5%)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 6 July 2012
- Deviations:
- yes
- Remarks:
- / different/higher acceptable body weight loss than in TG (10 instead of 5%)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Version / remarks:
- March 2003
- Deviations:
- not specified
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
FORM AS APPLIED IN THE TEST (if different from that of starting material)
liquid - Species:
- mouse
- Strain:
- CBA/Ca
- Remarks:
- Ola Hsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Envigo, Venray, The Netherlands
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 17 - 22 g
- Housing: 5 animals per cage, in IVC cages, type II L, polysulphone cages on Altromin saw fibre bedding
- Diet: Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water: tap water (sulphur acidified to a pH value of approx. 2.8), ad libitum, analysis was performed
- Acclimation period: at least 5 days
- Indication of any skin lesions: no
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12 / 12
- IN-LIFE DATES: From: 01 To: 23 June 2016 - Vehicle:
- other: aqua ad injectionem (AlleMan Pharma, lot no. 505651) containing 2% carboxymethyl cellulose (CMC, Alpha Aesar, lot no.: 10193024)
- Concentration:
- 6.25, 12.5 and 25% (w/v)
- No. of animals per dose:
- 5
- Details on study design:
- PRE-SCREEN TESTS:
In the pre-screening test, two concentrations (12.5 and 25% dissolved in aqua ad injection) were selected, and 25 μL of each dose formulation or the vehicle alone were applied to the entire dorsal surface of the ears of each animal, 2 mice for each concentration (one mouse for the vehicle control), once a day for 3 consecutive days. Animals were observed daily for clinical signs of systemic toxicity and local irritation at the application site. Furthermore, body weights and ear thickness measurements were performed (before initial application and on Day 6, ear thickness was additionally measured on Day 3). None of the animals showed any abnormalities or any signs of signifcant irritation (indicated by an erythema score ≥ 3 and / or an increase of more than 25% in ear thickness). All animals showed the expected weight development. No mortality was observed.
Based on these results and considering that 25% was the maximum attainable concentration, 25% (w/v) was selected as the highest test concentration for the main study. This concentration was expected not to induce systemic toxicity, nor to induce an increase in ear thickness exceeding 25% or to induce dermal erythema with a score of 3 or more, or more than 10% body weight loss.
- Compound solubility: 25% (maximum attainable concentration)
- Irritation: no irritation observed
- Systemic toxicity: no systemic toxicity observed
- Ear thickness measurements: less than 25% increase in ear thickness was observed
- Erythema scores: no specific findings (each test group, each time point)
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: 3H-methyl thymidine incorporation determined by ß-scintillation
- Criteria used to consider a positive response: A substance is regarded as a sensitizer in the LLNA, if the Stimulation Index (SI) is equal to or exceeding 3
TREATMENT PREPARATION AND ADMINISTRATION:
25 μL of each dose formulation were applied to the dorsal skin of each ear of each animal once a day for 3 consecutive days. On day 6 20 μCi 3H-methyl thymidine, contained in 250 μL of PBS (= 80 μCi/mL) was administered intravenously to each mouse via the tail vein. Approximately 5 h after administration local lymph nodes were collected, minced, washed and pooled. The pooled lymph node cells (LNC) were treated with approx. 1 mL of 5% Trichloroacetic acid (TCA) at approx. 4 °C overnight (approx. 18 h) before determination of the amount of 3H-methyl thymidine incorporation on day 7 (measured in a ß-counter). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Mean values and standard deviations were calculated.
- Positive control results:
- The positive control substance (25% hexyl cinnamic aldehyde (Batch number: MKBS3936V, SIGMA-ALDRICH, Germany) in aqua ad injectionem) induced a positive reaction, determined by a DPM/lymph node of 6859.7 compared to 700.5 DPM/lymph node in the vehicle control group, leading to a SI of 9.8. No abnormal clinical signs, erythema on the ears or body weight changes were observed. Only wet fur at the application site was observed in 1 animal from Day 2-5.
- Key result
- Parameter:
- SI
- Value:
- 1
- Test group / Remarks:
- 6.25% test group
- Key result
- Parameter:
- SI
- Value:
- 0.9
- Test group / Remarks:
- 12.5% test group
- Key result
- Parameter:
- SI
- Value:
- 1.2
- Test group / Remarks:
- 25% test group
- Parameter:
- SI
- Value:
- 9.8
- Test group / Remarks:
- positive control group
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA:
No significant lymph node proliferation (SI ≥ 3) was observed for the test item at treatment concentrations of 6.25, 12.5 and 25%, compared to the control.
DETAILS ON STIMULATION INDEX CALCULATION: SI = DPM/lymph node of a treated group divided by the DPM/lymph node of the vehicle control group (The measured DPM values were corrected with the background DPM value. The average of the measured DPM values of the scintillation fluid and TCA solution was used as background DPM value.)
EC3 CALCULATION: Based on the obtained results (SI < 3) no linear regression (using SI values) was performed for dose-response analysis and no EC3 value of the test item was calculated.
CLINICAL OBSERVATIONS:
No mortality or symptoms of systemic toxicity were observed in any treatment group. No signs of irritation (indicated by an erythema score ≥ 3) or any other local effect were observed in any treatment group. Topical application of the test substance led only to a slight increase in the mean DPM values of the the 25% treatment group. The following values (DPM/lymph node) were obtained: 700.5, 690.8, 652.9 and 861.5 in vehicle control (aqua ad injectionem), 6.25, 12.5 and 25% treatment group, respectively.
BODY WEIGHTS:
All animals showed the expected weight development, which includes a weight loss of up to 2 g throughout the study. - Interpretation of results:
- other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- CLP not classified
Reference
Table 1: Stimulation index in mice after application of the vehicle, test substance or positive control substance
Compound |
Concentration [%] |
Animal No. |
DPM/animal - mean background |
DPM/lymph node |
Stimulation index |
Vehicle |
100 |
1 |
1926.6 |
963.3 |
1.0 |
2 |
676.6 |
338.3 |
|||
3 |
1513.6 |
756.8 |
|||
4 |
1717.6 |
858.8 |
|||
5 |
1170.6 |
585.3 |
|||
Mean ± SD |
1401 ± 439.8 |
700.5 ± 219.9 |
|||
Test substance (in aqua ad injectionem) |
6.25 |
6 |
734.6 |
367.3 |
0.5 |
7 |
1900.6 |
950.3 |
1.4 |
||
8 |
1308.6 |
654.3 |
0.9 |
||
9 |
1608.6 |
804.3 |
1.1 |
||
10 |
1355.6 |
677.8 |
1.0 |
||
Mean ± SD |
1381.6 ± 386.1 |
690.8 ± 193.1 |
1.0 ± 0.3 |
||
12.5 |
11 |
1087.6 |
543.8 |
0.8 |
|
12 |
984.6 |
492.3 |
0.7 |
||
13 |
1556.6 |
778.3 |
1.1 |
||
14 |
1365.6 |
682.8 |
1.0 |
||
15 |
1534.6 |
767.3 |
1.1 |
||
Mean ± SD |
1305.8 ± 232.2 |
652.9 ± 116.1 |
0.9 ± 0.2 |
||
25 |
16 |
799.6 |
399.8 |
0.6 |
|
17 |
983.6 |
491.8 |
0.7 |
||
18 |
1717.6 |
858.8 |
1.2 |
||
19 |
2370.6 |
1185.3 |
1.7 |
||
20 |
2743.6 |
1371.8 |
2.0 |
||
Mean ± SD |
1723 ± 756.4 |
861.5 ± 378.2 |
1.2 ± 0.5 |
||
Positive control |
25 |
21 |
1926.6 |
963.3 |
14.4 |
22 |
676.6 |
338.3 |
9.4 |
||
23 |
1513.6 |
756.8 |
11.7 |
||
24 |
1717.6 |
858.8 |
8.0 |
||
25 |
1170.6 |
585.3 |
5.5 |
||
Mean ± SD |
13719.4 ± 4265.8 |
6859.7 ± 2132.9 |
9.8 ± 3.0 |
DPM = disintegrations per minute
HCA = hexyl cinnamic aldehyde
SD = standard deviation
Table 2: Body weight of mice after application of the vehicle, test substance or positive control substance
Compound |
Concentration [%] |
Animal No. |
Body weight |
||
Start of Study [g] |
End of Study [g] |
Change [g] |
|||
Vehicle |
100 |
1 |
19 |
20 |
1 |
2 |
21 |
21 |
0 |
||
3 |
22 |
23 |
1 |
||
4 |
20 |
20 |
0 |
||
5 |
21 |
21 |
0 |
||
Test substance |
6.25 |
6 |
21 |
22 |
1 |
7 |
18 |
18 |
0 |
||
8 |
21 |
21 |
0 |
||
9 |
22 |
22 |
0 |
||
10 |
19 |
19 |
0 |
||
12.5 |
11 |
18 |
20 |
2 |
|
12 |
19 |
21 |
2 |
||
13 |
18 |
18 |
0 |
||
14 |
18 |
18 |
0 |
||
15 |
20 |
21 |
1 |
||
25 |
16 |
17 |
17 |
0 |
|
17 |
18 |
19 |
1 |
||
18 |
19 |
18 |
-1 |
||
19 |
18 |
19 |
1 |
||
20 |
21 |
21 |
0 |
||
Positive control |
25 |
21 |
18 |
19 |
1 |
22 |
18 |
20 |
2 |
||
23 |
20 |
21 |
1 |
||
24 |
19 |
21 |
2 |
||
25 |
19 |
20 |
1 |
HCA = hexyl cinnamic aldehyde
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Skin sensitisation
The skin sensitising properties of the test substance were tested in a study according to OECD 429 and EU Method B.42 and in compliance with GLP (reference 7.4.1-1). The mice were exposed to different concentrations of the test substance (6.25, 12.5 and 25%) once a day for 3 consecutive days. The resulting Stimulation indices of 1, 0.9 and 1.2 for 6.25, 12.5 and 25% of the test substance, respectively, were below 3. Therefore, diammonium tartrate is not regarded as skin sensitizer.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.
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