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EC number: - | CAS number: -
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Endpoint summary
Administrative data
Description of key information
In a skin sensitisation Local Lymph Node Assay (LLNA) according to OECD TG 429 using phenol, mono- & distyrenated (LS 500) as test substance, a SI > 3 was observed for the 3% preparation. SI for the 30% preparation was 27. An EC3 of 1.67% was determined by linear interpolation of the 0.3% and 3% data points. Based on this data, LS 500 is considered to be a strong skin sensitiser.
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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Novares LS 500; phenol, styrenated
- Source and lot/batch No.of test material: RÜTGERS Novares GmbH, batch No. 28324
- Composition of test material: composition is specified in IUCLID Sect. 13 - Assessment reports under Certificate of Analysis_Novares LS 500_phenol, styrenated
- Substance type: organic
- Purity test date: 30.11.2012
- Stability under test conditions: no measured data; based on chemical structure assumed to be stable - Species:
- mouse
- Strain:
- Balb/c
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Breeding farm VELAZ s.r.o., Koleč u Kladna, Czech Republic
- Age at study initiation: 8 - 10 wks
- Weight at study initiation: 17 - 19 g
- Housing: macrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3
- Humidity (%): 30 – 70
- Photoperiod (hrs dark / hrs light): 12 / 12
- Vehicle:
- other: DAE 433
- Concentration:
- mixture of 40% dimethylacetamide, 30% acetone and 30% ethanol
- No. of animals per dose:
- 5
- Details on study design:
- RANGE FINDING TESTS:
- Compound solubility: dispersion
- Irritation: no
- Lymph node proliferation response: not examined
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response:
Stimulation index (SI) is ≥ 3
Response increases in dose-related manner
Criteria for irritation potential: individual and mean ear weight
TREATMENT PREPARATION AND ADMINISTRATION:
Days 1-3: 25 µL test suspension in DAE 433 , 1x on day 1, 2, and 3
Days 4 and 5: no treatment
Day 6: Injection of 250 μL of phosphate-buffered saline (PBS) containing 7.5 x105 Bq (c. 21 µCi) of 3H-methyl thymidine
into all test and control mice via the tail vein. Five hours later, the animals were killed.
- Positive control substance(s):
- other: DNCB (dinitrochlorbenzene, 0.5% (w/v) solution)
- Statistics:
- Non-parametric Kruskal-Wallis test, and then the non-parametric two-group Mann-Whitney rank test (probability level 0.05) was applied to all two-group comparisons [using software Statgraphic ® Centurion (version XV, USA)].
- Parameter:
- EC3
- Value:
- 1.67
- Parameter:
- SI
- Value:
- 2.56
- Test group / Remarks:
- 0.3% test substance in vehicle
- Parameter:
- SI
- Value:
- 3.43
- Test group / Remarks:
- 3% test substance in vehicle
- Parameter:
- SI
- Value:
- 27.07
- Test group / Remarks:
- 30% test substance in vehicle
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
Proliferation data were determined as mean (radioactivity counts - DPM) of five test animals per group
DETAILS ON STIMULATION INDEX CALCULATION
SI was calculated using the following equation: SI = mean of test groups (DPM) / mean of control group (DPM)
EC3 CALCULATION
Linear interpolation with EC3 = c + [(3–d)/(b–d)]×(a–c), where the data points lying immediately above and below the SI value of 3 on the LLNA dose–response plot having the coordinates (a,b) and (c,d), respectively.
(a = dose concentration immediately above SI=3, b = SI immediately above 3)
(c = dose concentration immediately below SI=3, d = SI immediately below 3) - Interpretation of results:
- Category 1A (indication of significant skin sensitising potential) based on GHS criteria
- Conclusions:
- In a LLNA according to OECD TG 429, an EC3 of 1.67 was determined. This requires phenol, styrenated (LS 500) to be classified as skin sensitising Cat. 1A.
Reference
Table 1: Individual and mean radioactivity in cell suspensions (Report Table 4)
Animal No. |
Activity (DPM) |
||||
NC (1-5) |
PC (6-10) |
30% (11-15) |
3% (16-20) |
0.3% (21-25) |
|
1 |
550.98 |
11374.69 |
13868.92 |
1764.06 |
1504.40 |
2 |
485.39 |
10401.94 |
15745.06 |
1472.17 |
1129.52 |
3 |
568.93 |
10347.82 |
13338.82 |
1552.57 |
1218.14 |
4 |
526.30 |
8837.38 |
15573.65 |
1811.12 |
1337.00 |
5 |
596.74 |
9493.34 |
15327.01 |
2756.16 |
1804.05 |
Group mean |
545.67 |
10091.03 |
14770.69 |
1873.02 |
1398.62 |
SI |
1.00 |
18.49 |
27.07 |
3.43 |
2.56 |
NC = vehicle control; PC = positive control
Table 2: Individual and average ear weights (Report Table 5)
Animal No. |
Weight of ear biopsies (milligrams) |
||||
NC (1-6) |
PC (7-12) |
30% (13-18) |
3% (19-24) |
0.3% (25-30) |
|
1 |
24.5 |
27.4 |
30.6 |
21.4 |
22.0 |
2 |
25.2 |
27.5 |
26.7 |
21.3 |
21.2 |
3 |
23.8 |
26.5 |
35.2 |
22.4 |
18.8 |
4 |
23.4 |
26.7 |
30.6 |
22.9 |
20.2 |
5 |
24.7 |
27.2 |
30.2 |
21.8 |
22.3 |
Group mean |
24.32 |
27.06* |
30.66* |
21.96* |
20.90* |
SD |
0.72 |
0.44 |
3.02 |
0.68 |
1.43 |
NC = vehicle control; PC = positive control
* statistically significant with p =< 0.05, Mann-Whitney test
Table 3: Summary table (Report Table 6)
Group |
Radioisotope incorporation in lymph nodes |
Ear weight |
|
Mean DPM |
SI |
Mean (mg) |
|
NC |
545.67 |
1.0 |
24.32 |
PC |
10091.03 |
18.49+ |
27.06 |
30% |
14770.69 |
27.07+ |
30.66 |
3% |
1873.02 |
3.43+ |
21.96 |
0.3% |
1398.62 |
2.56 |
20.90 |
Bold figures with + = values >= 3
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
One valid study is available to assess the skin sensitising potential of phenol, mono- & distyrenated (LS 500). This study is used as key study. Supporting evidence results from a study with the supporting substance phenol, methylstyrenated (LA 300).
Phenol, mono- & distyrenated (LS 500)
In a mouse local lymph node assay according to OECD TG 429 performed under GLP conditions using 0.3, 3, and 30% preparations of the test substance in vehicle (mixture of 40% dimethylacetamide, 30% acetone, and 30% ethanol), an increase of the Stimulation Index (SI) for the test groups over controls was observed (SI = 2.56, 3.43, and 27.07). For the concentrations 3% and 30% the SI was > 3 demonstrating a sensitising response of the test animals following the treatment with test substance. The mean ear weight was below (3% test group = 21.96 mg) and above (30% test group = 30.66 mg) the ear weight of the controls (24.32 mg). The SI > 3 for the 3% test group indicates sensitising potential of phenol, styrenated (Brabnikova/VUOS 2010). An EC3 of 1.67% can be calculated by linear interpolation between the data points 0.3% and 3% indicating a strong skin sensitising potential of phenol, mono- & distyrenated (LS 500).
Supporting evidence - Phenol, methylstyrenated (LA 300)
In a similar mouse LLNA with the supporting substance phenol, methylstyrenated, SI for the test groups were 2.26 (0.3%), 2.68 (3%), and 16.35 (30%), indicating a lower sensitising potential compared to phenol, mono- & distyrenated. Ear weight was lower for the 0.3% and 3% group (22.46 and 22.52 mg) and higher for the 30% group (33.18 mg) compared to controls (24.32 mg) (LA 300_Brabnikova/VUOS 2010). EC3 was determined to be 3.63%.
Based on the positive results of the mouse LLNA (Brabnikova/VUOS 2010), phenol, mono- & distyrenated is rated as a potential contact allergen.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
In a LLNA according to OECD TG 429 conducted under GLP conditions, an EC3 of 1.67% was determined. Based on criteria of Regulation (EC) No 1272/2008 (GLP regulation), phenol, mono- & distyrenated (LS 500) is classified as skin sensitising Cat. 1A (EC3 ≤ 2).
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