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EC number: 701-003-6 | 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
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- Nanomaterial specific surface area
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- Nanomaterial surface chemistry
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- Endpoint summary
- Stability
- Biodegradation
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- 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 sensitisation - In Vivo (LLNA)
MLA-3202 might be regarded as skin sensitizer.
However, a false positive outcome cannot be excluded.
Skin sensitisation - In Vivo (Modified Beheler Method)
Not a sensitizer in guinea pigs.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 25 Aug 16 to 14 Oct 16
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- The substance has been found to be surface active. The OECD guideline states that surface active substances have been found to cause false positives in the LLNA study; various comparative studies of the local lymph node assay, guinea pig maximization test, and in vitro methods confirm this to be the case. Furthermore, lymphocyte proliferation has also been shown to be influenced by several factors including vehicle selection. OECD recommended vehicles include: acetone/olive oil (AOO: 4 : 1 v/v), dimethylformamide, methyl ethyl ketone, propylene glycol, dimethyl sulphoxide, and dimethyl sulfoxide (DMSO). Several of these vehicles including AOO, DMSO, and propylene glycol have been shown to augment the LLNA response of certain chemicals. For example, AOO has been shown to give highly variable results when used as a vehicle in the LLNA. In addition, research suggests that olive oil itself may cause contact allergy in certain circumstances.. Therefore, it cannot be excluded that a non-specific stimulation of the lymph nodes occurred, not related to skin sensitization, and thus providing a false positive in this test. Based on these results and evaluation and according to the recommendations made in the test guidelines (including all amendments), MLA-3202 may possibly be regarded as skin sensitizer. However, a false positive outcome cannot be excluded, and further investigation work for this endpoint was required. Selection of the subsequent Buehler test was undertaken in order to further evaluate this endpoint, and the results confirm the conclusion that the LLNA provided a false positive result.
- Specific details on test material used for the study:
- No further details specified
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- Experimental AnimalsSpecies & Strain: Guinea Pig; Hartley-AlbinoJustification of Species: The guinea pig is conventionally used in skin sensitization studies to provide information on which human hazard can be judged, and is preferred by regulatory agencies.Source: Charles River, Hdq: Wilmington, MAQuantity & Sex: 2/sex (Range-fmding); 15/sex (Defmitive); females nulliparous & non-pregnantAcclimation Period: At least 5 daysDate Born/Date Received: 17 & 22 Jun 16 / 22 Aug 16Animal Identification: Ear punch & cage cardWeights When Tested: 388-563 gAnimal HusbandryCage Type: Stainless steel, suspended, wire bottom with plastic liner & beddingHousing: 1 - 5 per cage (males separate from females); enrichment providedEnvironmental ControlsSet to Maintain:20 ± 3 °C target temperature; 12-hr light/12-hr dark cycle; 30- 70% target humidity10+ air changes per hourActual Temp/Rel. Humidity: 16- 25°C / 50- 79%Food: LabDiet® 5025 Guinea Pig Diet; available ad libitumWater: Municipal water supply analyzed by TCEQ Water Utilities Division; available ad libitum from water bowlsAnimal husbandry and housing at STILLMEADOW, Inc. comply with standards outlined in "Guide for the Care and Use of Laboratory Animals" (NRC Publ.). No contaminants were expected to have been present in feed or water that would have interfered with or affected study results.
- Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- 0.4 mL
- Day(s)/duration:
- Once weekly for three weeks
- Adequacy of induction:
- not specified
- Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- 0.4 mL
- Day(s)/duration:
- 48 hours
- Adequacy of challenge:
- not specified
- No. of animals per dose:
- Two male and two female albino guinea pigs were selected for irritation range-finding.Naive control group (5/sex).Test group (10/sex).
- Details on study design:
- Irritation Range-Finding Two male and two female albino guinea pigs were selected for irritation range-finding to determine both maximum dose producing no more than moderate irritation, and maximum non-irritating dose.Concentrations tested in the range-finder were 100% (undiluted), and 75%, 50% and 25% v/v dilutions in DI water, with each animal receiving 0.4 mL of each concentration at different test sites.Preparation of AnimalsMales and females were selected for each of two treatment groups, designated as Naive control group (5/sex) and Test group (10/sex). On the day prior to each treatment, animals were prepared by clipping the back of the trunk free of hair to expose a sufficiently sized test area on each animal. Individual body weights were recorded on Days 0 and 31.Test Substance AdministrationBased on range-finding results, the dose administered was an application of 0.4 mL of undiluted test substance.For each induction treatment, Test group animals were treated by introducing test substance beneath -5 x 5 cm surgical gauze patch. Each gauze patch was placed laterally from the midline of the back on the left front quadrant of exposure area, held by a strip of clear polyethylene film placed over the patch and secured with non-irritating tape. At the end of the 6-hour exposure period, wrappings and patches were removed, and animals returned to their cages. Test animals were treated once weekly for three weeks (Days 1, 8 and 15) with 0.4 mL of undiluted test substance, using the same treatment regimen and test site location for all three inductions. Naive group animals remained untreated during induction phase of the study.Challenge TreatmentAfter a two-week rest period, all animals (both groups) were each challenged on Day 29 at a virgin test site with an application of 0.4 mL of undiluted test substance. The dose was applied in a manner identical to induction treatments, except the test site was placed laterally on the right rear quadrant of exposure area.Observations and Scoring MethodObservations for skin reactions at each test site were made -24 hours after each unwrap. In addition, observations for skin reactions were made -48 hours after both the first induction and the challenge unwraps.The scoring scale for grading skin reactions is presented as follows.Erythema ScoreNo reaction 0Very faint, usually non-confluent 0.5Faint, usually confluent 1Moderate 2Strong, with or without edema 3An average score for each time period was obtained by adding all scores for each time period and dividing by number of test sites scored for that time period. The test substance is considered a sensitizer if mean irritation scores, total number of animals with scores, and/or total number of scores for the virgin test site in the Test group after challenge treatment are appreciably greater than those for the Naive challenge group.
- Challenge controls:
- Not specified
- Positive control substance(s):
- yes
- Remarks:
- Alpha-Hexylcirmamaldehyde, >95%, CAS# 101-86-0,
- Positive control results:
- The mean score of 0.8 for the Test group after challenge treatment, when compared with the Naive control group mean score of 0.0, confmned sensitivity of guinea pigs to the positive control material.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0.4 mL
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- Non specified
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 0.4 mL
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- Non specified
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test substance produced no reaction in either Test animals or Naive control animals after the challenge treatment. Therefore, MLA-3202, Batch RC-1045, CAS 1454803-04-3 is not a sensitizer in guinea pigs.
- Executive summary:
A skin sensitization study was conducted on 15 male and 15 female short-haired albino guinea pigs to determine if test substance MLA-3202, Batch RC-1045, CAS 1454803-04-3 produced a sensitizing reaction.
The study was conducted in accordance with US EPA OCSPP 870.2600 and OECD 406 guidelines.
Males and females were assigned to each of two groups, designated Naive control (5/sex) and Test (10/sex).
Naive control group animals remained untreated during induction phase of the study. Test group animals were treated with 0.4 mL of undiluted test substance (selected from range-finding). Test animals were treated once weekly for three weeks, for a total of three inductions. After a two-week rest period, all animals (both groups) were challenged at a virgin test site with an application of 0.4 mL of undiluted test substance.
The test substance produced no reaction in either Test animals or Naive control animals after the challenge treatment. Therefore, MLA-3202, Batch RC-1045, CAS 1454803-04-3 is not a sensitizer in guinea pigs.
Reference
Range-finder
Animal Number |
Body Wt (g) |
Observation Time After Treatment |
|||||||
24 Hour Score* |
48 Hour Score* |
||||||||
Front Site |
Rear Site |
Front Site |
Rear Site |
||||||
31-M |
415 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
32-M |
420 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
33-F |
405 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
34-F |
398 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
* - Observations made for erythema; M – Male; F – Female
Level Selected for Induction: 100% as received
Level Selected for Challenge: 100 % as received
Skin Reaction Scores
Animal No. |
Hours After Day of Treatment |
||||||
Induction Treatments LF |
|
Challenge RR |
|||||
Day 1 |
Day 8 |
Day 15 |
Day 29 |
||||
24 hr |
48 hr |
24 hr |
48 hr |
24 hr |
48 hr |
||
Naïve Control 41-M 42-M 43-M 44-M 45-M
46-F 47-F 48-F 49-F 50-F
Test 51-M 52-M 53-M 54-M 55-M
56-F 57-F 58-F 59-F 60-F
61-M 62-M 63-M 64-M 65-M
66-F 67-F 68-F 69-F 70-F |
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0 |
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0 |
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0 |
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0 |
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0 |
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0 |
|
|
|||||||
M – Male; F – Female |
|||||||
LF – Left Front test site; RR – Right Rear test site |
|||||||
Note: Observations were made for erythema |
Body Weights
Animal Number |
Day of Study |
Animal Number |
Day of Study |
||
Day 0 |
Day 31 |
Day 0 |
Day 31 |
||
Naïve Control |
|||||
41-M |
516 |
669 |
46-F |
407 |
522 |
42-M |
502 |
667 |
47-F |
388 |
508 |
43-M |
449 |
646 |
48-F |
406 |
558 |
44-M |
481 |
680 |
49-F |
421 |
528 |
45-M |
479 |
643 |
50-F |
469 |
577 |
Test |
|||||
51-M |
549 |
793 |
61-M |
498 |
560 |
52-M |
494 |
707 |
62-M |
466 |
584 |
53-M |
476 |
756 |
63-M |
474 |
579 |
54-M |
464 |
641 |
64-M |
506 |
631 |
55-M |
563 |
873 |
65-M |
505 |
557 |
56-F |
449 |
555 |
66-F |
435 |
696 |
57-F |
440 |
564 |
67-F |
451 |
715 |
58-F |
434 |
526 |
68-F |
464 |
781 |
59-F |
443 |
569 |
69-F |
453 |
712 |
60-F |
429 |
547 |
70-F |
442 |
718 |
M – Male; F – Female Note: Weights are in grams |
Positive Control Skin Reaction Scores
Animal No. |
Hours After Day of Treatment |
||||||
Induction Treatment LF |
|
Challenge RR |
|||||
Day 1 |
Day 8 |
Day 15 |
Day 29 |
||||
24 hr |
48 hr |
24 hr |
24 hr |
24 hr |
48 hr |
||
Naïve Control 41-M 42-M 43-M 44-M 45-M
46-F 47-F 48-F 49-F 50-F
Test 51-M 52-M 53-M 54-M 55-M
56-F 57-F 58-F 59-F 60-F |
0 0 0 0 0
0 0 0 0 0 |
0 0 0 0 0
0 0 0 0 0 |
0 0 0 0 0
0 0 0 0 0 |
0.5 0 0 0.5 0
0.5 0 0 0.5 1 |
0 0 0 0 0
0 0 0 0 0
2 0.5 0.5 1 1
0.5 1 1 0.5 1 |
0 0 0 0 0
0 0 0 0 0
1 0 0.5 0.5 1
0.5 0.5 1 0 1 |
|
|
|||||||
Male – Male; F – Female; LF – Left Front test site; RR – Right Rear test site |
|||||||
Note: Observations were made for erythema |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Skin sensitisation - In Vivo (LLNA)
In the main study, three experimental groups of five female CBA/J mice were treated with test item concentrations of 10, 25 or 50% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone (Acetone/Olive oil (4:1 v/v)). Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintegrations per minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.
No erythema of the ears was noted for any of the animals. Scaliness was noted for the ears of the animals dosed at 25 and 50% on Day 6, which was considered not to have a toxicologically significant effect on the activity of the nodes.
No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.
Enlarged auricular lymph nodes were found for the animals dosed at 50%. The nodes of the other dose groups and the control group were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals.
Mean DPM/animal values for the experimental groups treated with test item concentrations 10, 25 and 50% were 822, 1219 and 3222 DPM, respectively. The mean DPM/animal value for the vehicle control group was 531 DPM. The SI values calculated for the test item concentrations 10, 25 and 50% were 1.5, 2.3 and 6.1, respectively.
These results indicate that the test item could elicit a SI ≥ 3. The data showed a dose-response and an EC3 value (the estimated test item concentration that will give a SI =3) of 30% was calculated.
However, additional information was provided by the Sponsor stating that “following the LLNA study, the surface tension study for MLA-3202 showed it to be a surface active substance”. The OECD guideline state that surface active substances have been found to cause false positives in the LLNA study. Therefore, it cannot be excluded that a non-specific stimulation of the lymph nodes occurred, not related to skin sensitization. The substance has been found to be surface active. The OECD guideline states that surface active substances have been found to cause false positives in the LLNA study; various comparative studies of the local lymph node assay, guinea pig maximization test, and in vitro methods confirm this to be the case. Furthermore, lymphocyte proliferation has also been shown to be influenced by several factors including vehicle selection. OECD recommended vehicles include: acetone/olive oil (AOO: 4 : 1 v/v), dimethylformamide, methyl ethyl ketone, propylene glycol, dimethyl sulphoxide, and dimethyl sulfoxide (DMSO). Several of these vehicles including AOO, DMSO, and propylene glycol have been shown to augment the LLNA response of certain chemicals. For example, AOO: 4 : 1 v/v has been shown to give highly variable results when used as a vehicle in the LLNA. In addition, research suggests that olive oil itself may cause contact allergy in certain circumstances.. Therefore, it cannot be excluded that a non-specific stimulation of the lymph nodes occurred, not related to skin sensitization, and thus providing a false positive in this test. The test is therefore considered unreliable, and a further investigation using an alternative method was enacted.
Based on these results and evaluation and according to the recommendations made in the test guidelines (including all amendments), MLA-3202 might be regarded as skin sensitizer.
However, a false positive outcome cannot be excluded.
Skin sensitisation - In Vivo (Modified Buehler Method)
Study was conducted on 15 male and 15 female short-haired albino guinea pigs to determine if test substance MLA-3202, Batch RC-1045, CAS 1454803-04-3 produced a sensitizing reaction.
The study was conducted in accordance with US EPA OCSPP 870.2600 and OECD 406 guidelines.
Males and females were assigned to each of two groups, designated Naive control (5/sex) and Test (10/sex).
Naive control group animals remained untreated during induction phase of the study. Test group animals were treated with 0.4 mL of undiluted test substance (selected from range-finding). Test animals were treated once weekly for three weeks, for a total of three inductions. After a two-week rest period, all animals (both groups) were challenged at a virgin test site with an application of 0.4 mL of undiluted test substance.
The test substance produced no reaction in either Test animals or Naive control animals after the challenge treatment. Therefore, MLA-3202, Batch RC-1045, CAS 1454803-04-3 is not a sensitizer in guinea pigs.
Justification for classification or non-classification
Skin sensitisation - In Vivo (Modified Buehler Method)
The test substance produced no reaction in either Test animals or Naive control animals after the challenge treatment. Therefore, MLA-3202, Batch RC-1045, CAS 1454803-04-3 is not a sensitizer in guinea pigs and does not fulfill the reuqirements for classification under CLP.
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