Sodium 5-oxo-1-palmitoyl-L-prolinate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28.August.2002-02.September.2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

The relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the study plan. CIT became CiToxLAB France, data referring to expiry date or stability of the test item were missing to characterize the test item.

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

no

Remarks:

No Study Director was assigned from 06 October 2004 to 05 March 2014. The final study plan was not signed by the Study Monitor and the sponsor did not provide expiry data of the test item. These deviations were considered not to be GLP compliance.

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

Test item
Supplier : Société Seppic
Name : LCA02011
Batch number
- Study plan : 1179001
- labeling : none
Description : brown liquid at receipt and then solid
Container : one plastic flask
Date of receipt :05 August 2002
Storage condition : at room temperature

At the finalisation of the study report, no analytical certificate was available. Consequently, characterisation of the test item was not complete since no expiry date and no stability data were given.
The batch No." 1179001" which was absent from the label on the container was confirmed by the Study Monitor on a statement dated 22 May 2003.

Vehicle
The vehicle used was a mixture acetonefolive oil (4/1, viv): acetone, batch No. 0126152 (Carlo Erba, Rueil-Malmaison, France) and olive oil, batch No. 050K6072 (Sigma, Saint-Quentin-Fallavier, France).

Reference item
The reference item was O.-hexylcinnamaldehyde (HCA), batch No. 01.016AQ (Aldrich, Saint-Quentin-Fallavier, France), dissolved in a mixture acetonefolive oil (4/1, Vfw) at the concentration of 25% (v/v). The preparation was made freshly on the morning of administration and any unused material was discarded that same day.

Reactive used for the proliferation assay
The reactive used for the proliferation assay was IHI methyl-thymidine (H-TdR). batch No. B464B(Amersham, Les Ulis, France).
Three days before the injections, the required quantity of H-TdR was diluted in 0.9% NaCl
(20 uCi in 250 L of 0.9% NaCl per animal). The obtained solution was stored at +4°C and protected from light before use.

Species:

mouse

Strain:

CBA:J

Sex:

female

Details on test animals and environmental conditions:

Animals:
Animals Species, strain and Sex: CBAJ mouse, nulliparous and non-pregnant females.
Reason for this choice: species generally accepted by regulatory authorities for this type of study. Females have been chosen since this sex is recommended by regulatory authorities for this type of study.
Breeder:Janvier, Le Genest-Saint-Isle, France.
Number: 20 females.
Age/weight: on the first day of treatment, the animals were approximately 9 weeks old and had a mean body weight I standard deviation of 20.6 g + 0.7 g.
Acclimation: at least 5 days before the beginning of the study,
Allocation:on day 1, animals were assigned to the treatment groups by hand procedure.
Identification: individually by a number on the tail,

Environmental conditions:
The conditions in the animal room were set as follows:
temperature : 22 + 2°C
relative humidity : 30 to 70%,
light/dark cycle : 12h/12 h,
ventilation : approximately 12 cycles/hour of filtered, non-recycled air. The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment are verified and calibrated at regular intervals. The animals were housed individually in disposable crystal polystyrene cages (22.00 cm x 8.50 cm x 8.00 cm). Each cage contained autoclaved sawdust (SICSA, Alfortville, France). Sawdust is analysed by the Supplier for composition and contaminant levels.

Food and water
All animals had free access to A04 C peleted diet (UAR, Villemoisson, Epinay-sur-Orge, France) and tap water (filtered using a 0.22 micron filter) contained in bottles. Each batch of food is analyzed by the supplier for composition and contaminant levels. The diet formula is presented in Appendix 1.
Bacteriological and chemical analyses of water, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines) are performed regularly by external laboratories. The results of these analyses are archived at CiToxLAB France.
No contaminants are known to be present in the diet, drinking water or sawdust at levels which may be expected to interfere with or prejudice the outcome of the study.

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

1,3 and 5%

No. of animals per dose:

4 animals

Details on study design:

PRE-SCREEN TESTS:
-Solubility: The test item at the concentration of 5% was freely soluble in the first recommended vehicle, acetone/olive oil (4/1, v/v)
- Irritation: The test item, vehicle or reference item were applied over the ears (25 microl per ear) for three consecutive daus (days 1,2 and 3). After 2 days of resting, the proliferation of the lymph node cells in the lymph node draining the application site was measured by incorporation of tritiated methyl thymidine (day 6). The obtained values were used to calculate Stimulation Indices (SI).
- Ear thickness measurements: days 1,2,3 and 6

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: The test item was considered as a skin sensitizer when the SI for a dose group is > 3. Other relevant criteria such as cellularity, radioactivity levels and ear thickness were also taken into account for the interpretation of results. Whenever possible, calculation of the EC3 value (theoretical concentration of the test item resulting in a SI value of 3) was performed on the basis of a dose-effect response.

TREATMENT PREPARATION AND ADMINISTRATION:
Treatment preparation
The vehicle used was a mixture acetonefolive oil (4/1, viv): acetone, batch No. 0126152 (Carlo Erba, Rueil-Malmaison, France) and olive oil, batch No. 050K6072 (Sigma, Saint-Quentin-Fallavier, France).

The test item was prepared in the vehicle at the chosen concentrations. The concentrations were expressed in % (wiv). All dosage form preparations were made freshly on the morning of administration and stored under nitrogen gas (on days 2 and 3). Any unused material was discarded that same day.

The reference item was O.-hexylcinnamaldehyde (HCA), batch No. 01.016AQ (Aldrich, Saint-Quentin-Fallavier, France), dissolved in a mixture acetonefolive oil (4/1, Vfw) at the concentration of 25% (v/v). The preparation was made freshly on the morning of administration and any unused material was discarded that same day.

The reactive used for the proliferation assay was IHI methyl-thymidine (H-TdR). batch No. B464B(Amersham, Les Ulis, France).
Three days before the injections, the required quantity of H-TdR was diluted in 0.9% NaCl
(20 uCi in 250 L of 0.9% NaCl per animal). The obtained solution was stored at +4°C and protected from light before use.

Administration
On days 1, 2 and 3, a dose-volume of 25 L of the control or dosage form preparations was applied to the dorsal surface of both cars, using an adjustable pipette fitted with a plastic tip. In order to avoid licking and to ensure an optimized application of the test materials, the animals were placed under light isoflurane anesthezia during the administration, No massage was performed but the tip was used to spread the preparation over the application sites. No rinsing was performed between each application.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

no data

Positive control results:

In the positive control group given HCA at the concentration of 25%, an increase in cellularity and a stimulation index exceeding the threshold value of 3 (SI= 13.53) were noted. The study was therefore considered valid.

Key result

Parameter:

SI

Value:

ca. 13.53

Test group / Remarks:

positive control / concentration 25%

Key result

Parameter:

SI

Value:

ca. 1.22

Test group / Remarks:

treated group / concentration 1%

Key result

Parameter:

SI

Value:

ca. 1.44

Test group / Remarks:

treated group / concentration 3%

Key result

Parameter:

SI

Value:

ca. 1.55

Test group / Remarks:

treated group / concentration 5%

Key result

Parameter:

EC3

Value:

ca. 22.2

Test group / Remarks:

The EC3 value (%) of the test item calculated from the SI values obtained at three tested concentrations

Cellular proliferation data / Observations:

Proliferation Assay:
The quantity of cells obtained in each group was satisfactory and the cellularity correlated with incorporation of H-TdR. The cell viability was higher than 80% in each group.
In the positive control group given HCA at the concentration of 25%, an increase in cellularity and a stimulation index exceeding the threshold value of 3 (SI it 3.53) were noted. The study was therefore considered valid.
In the treated groups, a very slight dose-related increase in the stimulation index but which never reached the threshold positive value of 3 was noted. Therefore, under our experimental conditions, the test item at concentrations a 5% does not induce delayed contact hyperSensitivity in the murine Local Lymph Node Assay.

Determination of the EC3 value:
The EC3 value of the test item calculated from the SI values obtained at the three testedi concentrations was equal to 22.2% (see Appendix 2). However, as the maximum concentration tested in this study was 5%, further investigations at concentrations higher than 5% may be necessary to confirm this EC3 value.

Interpretation of results:

GHS criteria not met

Conclusions:

Under our experimental conditions, the test item LCA02011 should not be considered as a skin sensitizer.

Executive summary:

The aim of this study was to evaluate the potential of the test item ICA02011 to induce delayed contact hypersensitivity using the murine Local Lymph Node ASSay (LLNA).

Methods

At the request of the Sponsor, twenty female CBAJ mice were allocated to five groups of four animals each:

• three treated groups receiving the test item LCA02011 at the concentrations of 1, 3 and 5%,


• one negative control group of four animals receiving the vehicle (mixture acetonefolive oil (471)),


• one positive control group receiving the reference item, O.-hexylcinnamaldehyde (HCA), a moderate sensitizer, at the concentration of 25%.

The test item, vehicle or reference item were applied over the ears (25 u per ear) for three consecutive days (days 1, 2 and 3). After 2 days of resting, the proliferation of the lymph node cells in the lymph node draining the application site was measured by incorporation of tritiated methyl thymidine (day 6). The obtained values were used to calculate Stimulation Indices (SI).

The irritant potential of the test item was assessed in parallel by measurement of ear thickness on days i. 2, 3 and 6.

Results

At the request of the Sponsor, the test item was tested at the maximum concentration of 5%. The test item at the concentration of 5% was freely soluble in the first recommended vehicle, acetonefolive oil (4/1, viv).

Systemic clinical signs and mortality

No mortality and no clinical signs were observed during the study.

Local irritation

No cutaneous reactions and no increase in ear thickness were observed in the animals of the treated groups.

Proliferation assay

In the treated groups, a very slight dose-related increase in the stimulation index but which never reached the threshold positive value of 3 was noted. Therefore, under our experimental conditions, the test item LCA02011 at concentrations < 5% did not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay.

The EC value of the test item calculated from the SI values obtained at the three tested concentrations was equal to 22.2% (see Appendix 2). However, as the maximum concentration tested in this study was 5%, further investigations at concentrations higher than 5% may be necessary to confirm this EC3 value.

Conclusion

Under our experimental conditions, the test item LCA02011 should not be considered as a skin Sensitizer.

 

 

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19.May.2008-20.June.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

Environmental parameters: A temperature of 24°C was registered instead of 23°C (maximal limit) as planned in the experimental protocol. This deviation did not, in any case, influence the development and the results of the study.

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

No in vitro test was proposed because this guinea pig test was done in 2004 and no in vitro test existed at that time (OECD tests n°442 C and D adopted in 2015)

Specific details on test material used for the study:

Sponsors identification: LCA08009
Date received: 14 May 2008
Container : plastic flask (n=1)
Form: liquid
Quantity : 142.44 g (container + contents)
Colour: brown
Batch no : LCA08009
Storage : room temperature
Purity: 30%
It was identified under the code number: PH-08/0227.
The test item was considered as 100% for the study.
Informations concerning the identity, purity and stability of the test item are the responsibility of the Sponsor. A safety data sheet and an information data sheet concerning the test item were provided by the study monitor.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Methodology:
Guideline n°406, in a first step 5 animals were retained for the control group and 10 for the treated one. In these conditions, if results enable an interpretation, the test can be validated. On the contrary, it must be completed by another test consisting in 5 control and 10 treated animals.

Housing:
The animals were housed either in groups of 2 or 3 in polycarbonate containers, the flooring of which was covered with dust-free cuttings and the top fitted a stainless steel lid with a feeding device and drinking device of 500 mL.
The environmental parameters of the main test were: - Temperature: between 19°C and 24°C - Relative humidity: between 40% and 70% - Lighting time; 12 hours daily - rate of air exchange: at least ten changes per hour.

Food and drink:
The drinking water (tap water from public distribution system) and food were supplied freely.
Microbiological verification and chemical analysis were conducted every six months by the Institut Européen de l'Environnement de Bordeaux (I.E.E.B.).

Preparation of animals
For the main study, 15 female albinoguinea pigs of Dunkin-Hartley strain, supplied by Charles River (F-69592 L’Arbresle) weighed between 231 g and 263 g at the beginning of the test and were 4 weeks old.
Prior to the test, the animals were kept for a minimum acclimatisation period of 5 days, under stabling and nutritional conditions identical to those of the test.
Before the experimentation process, they were identified individually by marking with picric acid and a tattoo placed on their ear. The animals were carefully shorn before each test item application:
on the inter-scapular zone for the induction phase, on the dorso-lumbar Zone for the challenge phase. At least 3 hours before the first reading (challenge phase) they were shorn a second time in this dorsolumbar zone.
The animals were weighed at the beginning and at the end of the study.

Route:

intradermal and epicutaneous

Concentration / amount:

Intradermal Induction:
Day 0
After shearing the scapular zone, three (3) pairs of intradermal injections (D) of 0.1 mL were performed on the scapular zone in such a way as an injection on each pair is placed to either side of the spine as follows:
GROUP 1 (Negative control):
e 2 ID: Freund's Complete Adjuvant diluted at 50% in isotonic sodium chloride.
e 2 ID: isotonic sodium chloride
0 2 ID: a mixture with equal volumes vsv:
- Freund's Complete Adjuvant at 50% and isotonic sodium chloride,
GROUP 2 (Treated):
to 2 ID: Freund's Complete Adjuvant diluted by 50% in isotonic sodium chloride,
o 2 ID; test item at 1.56%,
o 2 ID a test mixture in equal volumes viv :
- Freund's Complete Adjuvant at 50% and the test item at 3, 125%.

Topical Induction:
Day 6 The scapular zone of all the animals in each group, shorn beforehand, was brushed with a solution of sodium lauryl sulfate at 10% in thick vaseline, in order to create a local irritation.
Day 7 A topical application under occlusive dressing for 48 hours was performed on the injection sites of each animal.
GROUP 1 (Negative control): 0.5 mL of distilled water
GROUP 2 (treated): 0.5 mL of the test item at 100%

Day(s)/duration:

The induction phase lasts 7 days

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

sample cup containing the test item at 25% (MNIC) and at 12.5% (1/2 MNIC)

Day(s)/duration:

24 hours for each dose

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Negative control group: 5 animals
Treated group: 10 animals

Details on study design:

Induction phase
Intradermal Induction:
Day 0
After shearing the scapular zone, three (3) pairs of intradermal injections (D) of 0.1 mL were performed on the scapular zone in such a way as an injection on each pair is placed to either side of the spine as follows:
GROUP 1 (Negative control):
2 ID: Freund's Complete Adjuvant diluted at 50% in isotonic sodium chloride.
2 ID: isotonic sodium chloride
2 ID: a mixture with equal volumes vsv:
- Freund's Complete Adjuvant at 50% and isotonic sodium chloride,
GROUP 2 (Treated):
2 ID: Freund's Complete Adjuvant diluted by 50% in isotonic sodium chloride,
2 ID; test item at 1.56%,
2 ID a test mixture in equal volumes viv :
- Freund's Complete Adjuvant at 50% and the test item at 3, 125%.
2nd Topical Induction:
Day 6 The scapular zone of all the animals in each group, shorn beforehand, was brushed with a solution of sodium lauryl sulfate at 10% in thick vaseline, in order to create a local irritation.
Day 7 A topical application under occlusive dressing for 48 hours was performed on the injection sites of each animal.
GROUP 1 (Negative control): 0.5 mL of distilled water GROUP 2 (treated): 0.5 mL of the test item at 100%

Rest phase
The animals of both groups were left for 10 days.

Challenge phase
Day 20 The experimental procedure of this phase was identical for both groups GROUP 1 (Negative control) and GROUP 2 (Treated) submitted to this experimentation: on the previously shorn dorso-lumbar zone, an application on either side of the spine, under occlusive dressing, was performed during 24 hours:
- 1 sample cup containing the test item at 25% (MNIC) and at 12.5% (1/2 MNIC)

Challenge controls:

The Group 1 (negative control) was submitted to the same experimentation as Group 2 (treated group) during the challenge phase.

Positive control substance(s):

yes

Remarks:

alpha-hexylcinnamaldehyde

Positive control results:

In conclusion, in view of these results, under these experimental conditions, the substance O-Hexylcinnamaldehyde: must be classified R 43 “may cause sensitization by skin contact' in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45. This substance must be characterised by the symbol “X” and the warming label “Irritant”.
In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must be classified in category 1 "Skin sensitisation'. The signal word “Warning” and hazard statement H317 “May cause an allergic skin reaction' are required.

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

25 %

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Skin reaction
Score 1: 2 (treated groups 1), 0 (treated group 2), 3 (treated group 3)
Score 2: 8 (treated group 1), 1 (treated group 2), 4 (treated group 3)
Score 3: 0 (treated group 1), 9 (treated group 2), 2 (treated group 3)

Remarks on result:

other: Reading: 1st reading ; Hours after challenge: 24.0 ; Group: positive control ; Dose level: 25% ; No. with + reactions: 10 (treated groups 1 and 2), 9 (treated group 3) ; Total no. in group: 10

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

25 %

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

Skin reaction
Score 1: 7 (treated groups 1 and 2), 5 (treated group 3)
Score 2: 0 (treated group 1), 3 (treated group 2), 1 (treated group 3)
Score 3: 0 (treated groups 1, 2 and 3)

Remarks on result:

other: Reading: 1st reading ; Hours after challenge: 48.0 ; Group: positive control ; Dose level: 25% ; No. with + reactions: 7 (treated group 1), 10 (treated group 2), 6 (treated group 3) ; Total no. in group: 10

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

50 %

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Skin reaction
Score 1: 1 (treated group 1), 0 (treated group 2), 7 (treated group 3)
Score 2: 9 (treated group 1), 0 (treated group 2), 1 (treated group 3)
Score 3: 0 (treated group 1), 10 (treated group 2), 2 (treated group 3)

Remarks on result:

other: Reading: 1st reading ; Hours after challenge: 24.0 ; Group: positive control ; Dose level: 50 % ; No. with + reactions: 10 (treated groups 1, 2 and 3) ; Total no. in group: 10

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

50 %

No. with + reactions:

9

Total no. in group:

10

Clinical observations:

Skin reaction
Score 1: 6 (treated group 1), 7 (treated group 2), 4 (treated group 3)
Score 2: 3 (treated group 1), 2 (treated group 2), 1 (treated group 3)
Score 3: 0 (treated groups 1, 2 and 3)

Remarks on result:

other: Reading: 1st reading ; Hours after challenge: 48.0 ; Group: positive control ; Dose level: 50 % ; No. with + reactions: 9 (treated groups 1 and 2), 5 (treated group 3) ; Total no. in group: 10

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

25%

No. with + reactions:

1

Total no. in group:

5

Clinical observations:

20% of positive responses >or= to 1

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

25%

No. with + reactions:

1

Total no. in group:

5

Clinical observations:

20% of positive responses >or= to 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

12.5%

No. with + reactions:

2

Total no. in group:

5

Clinical observations:

40% of positive responses >or= to 1

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

12.5%

No. with + reactions:

1

Total no. in group:

5

Clinical observations:

20% of positive responses >or= to 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25%

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

20% of animal sensitized

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25%

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

0% of animal sensitized

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

12.5%

No. with + reactions:

2

Total no. in group:

10

Clinical observations:

0% of animal sensitized

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

12.5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

0% of animal sensitized

Interpretation of results:

GHS criteria not met

Conclusions:

In view of these results, under these experimental conditions, the test item LCA08009 must not be classified, in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must not be classified in category l. No signal word and hazard statement are required.

Executive summary:

The aim of the study was to evaluate the possible allergenic activity of the test item LCA08009 after intradermal injection and topical administration in guinea pigs. After induction (intradermal injection at 1.56% and topical application at 100%) of 10 Guinea Pigs of treated group with the test item LCA08009 and a 10-day rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test item diluted at 25% and at 12.5% in distilled water. The experimental protocol was established according the O.E.C. D. guideline n°406 dated July 17, 1992 and the method B.6 of the E.E.C. n°96/54 dated July 30", 1996.

Slight to moderate erythema was recorded, in respectively 40% (4/10) and 10% (1/10) of the animals from the treated group, 24 and 48 hours after the challenge phase, on the treated areas at 25%. Moderate erythema was noted in 20% (1/5) of the animals from the negative control group, 24 and 48 hours after the challenge phase, on the treated area at 25%.

Slight erythema was recorded, in 20% (2/10) of the animals from the treated group, 24 hours after the challenge phase, on the treated areas at 12.5%. This reaction was totally reversible at the reading time 48 hours. Slight to moderate erythema was noted, in respectively 40% (2/5) and 20% (1/5) of the animals from the negative control group, 24 and 48 hours after the challenge phase, on the treated area at 12.5%.

In conclusion, in view of these results, under these experimental conditions, the test item LCA08009 must not be classified, in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required, In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must not be classified in category l. No signal word and hazard statement are required.

 

 

Reference 3

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin sentisation

In conclusion, in view of these results, under these experimental conditions, the test item LCA08009 must not be classified, in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required, In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must not be classified in category l. No signal word and hazard statement are required.