2-morpholinoethanesulphonic acid

Endpoint summary

Description of key information

In a GLP-study according to OECD TG 429 (Local Lymph Node Assay), the substance did not induce any adverse effects and is therefore considered to be not skin sensitising (7.4.1 -1). The study was performed with the hydrate form of the substance (CAS 1266615-59-1). However, same results are expected for the anhydrous form (CAS 4432-31-9).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-09-14 to 2016-09-21

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:

2010

Deviations:

yes

Remarks:

Deviation in sample preparation without any presumed effect on the study

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

2012

Deviations:

yes

Remarks:

Deviation in sample preparation without any presumed effect on the study

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: TOXI COOP ZRT. Cserkesz u. 90., 1103 Budapest, Hungary
- Females nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: SPF
- Age at study initiation: 9 - 11 weeks
- Weight at study initiation: 17.9 - 21.0 g
- Fasting period before study: unknown
- Housing: group caging (4 mice/cage), Type II. Polypropylene / polycarbonate
- Diet: ad libitum, ssniff® Rat/Souris-Elevage E complete diet for rats and mice
- Water: ad libitum, tap water
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): not available
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

other: Pluronic

Concentration:

2.5, 5, 10%

No. of animals per dose:

4

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: yes (using seven recommended solvents)
- Irritation: no irritation was observed for the three concentration 2.5, 5 and 10% in a preliminary test
- Systemic toxicity: no toxicity was observed for the three concentration 2.5, 5 and 10% in a preliminary test
- Ear thickness measurements: no changes in ear thickness were observed for the three concentration 2.5, 5 and 10% in a preliminary test
- Erythema scores: all 0 for all concentrations, mice and time points (days 1, 2, 3, 4, 5, 6)

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: animals were assigned randomly achieving body weight homogeneity between groups
- Criteria used to consider a positive response: stimulation index of one concentration > 3

TREATMENT PREPARATION AND ADMINISTRATION: 25 µL of the three respective formulations (substance dissovled in Pluronic) were applied to the dorsal surface of each ear using a pipette

Positive control substance(s):

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

Statistics:

none

Positive control results:

Stimulation index (SI) of (w/v) hexyl cinnamic aldehyde: 6.7

Key result

Parameter:

SI

Value:

0.7

Test group / Remarks:

2.5%

Key result

Parameter:

SI

Value:

2.3

Test group / Remarks:

5%

Key result

Parameter:

SI

Value:

1.2

Test group / Remarks:

10%

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
Disintegration per minute (per mouse (average)):
vehicle control: 772.8
2.5%: 513.0
5%: 1759.3
10%: 894.5

DETAILS ON STIMULATION INDEX CALCULATION: ratio of DPM/mouse of test concentrations and vehicle control

EC3 CALCULATION: not applicable

CLINICAL OBSERVATIONS: no irritation or other effects observed

BODY WEIGHTS: no treatment related effects

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present assay, the test item at the maximum feasible concentration of 10 % and also at concentrations of 5 % or 2.5 % (w/v) was shown to have no skin sensitization potential in the Local Lymph Node Assay.

Executive summary:

A study according OECD TG 429 was performed to evaluate the skin sensitising potential of the test item. A formulation evaluation and a Dose Range Finding test (DRF) were performed to find an appropriate vehicle and the maximum applicable concentration according to the relevant guidelines. Solubility of the test item in vehicles preferred in the LLNA was evaluated and concentration series of 100 %, 50 %, 25 %, 10 % etc. were used. The maximum attainable concentration (based on solubility) was 10 % (w/v) in aqueous 1 % (w/v) Pluronic®PE 9200 (Plu). According to results of the DRF, where no adverse effect was observed up to this maximum concentration, the test item was examined in the main test as 10 %, 5 % or 2.5 % (w/v) formulations in the selected vehicle of Plu. Appropriate positive control (alpha-Hexylcinnamaldehyde, HCA), furthermore two negative control groups dosed with the vehicles of the test and positive control groups, respectively, were employed. The positive control item (25 % (w/v) HCA in Acetone:Olive oil 4:1 (v/v) mixture, AOO) induced significant stimulation over the relevant control (SI = 6.7) thus confirming the validity of the assay. No mortality was observed during the main test. No significant, treatment related effect on body weights or any other sign of systemic toxicity were observed in any treatment group. No signs of irritation (monitored by erythema scoring) or any other local effect were observed at the treatment site (ears) in any treatment group. No significantly increased lymphoproliferation (indicated by an SI ≥ 3) compared to the relevant control (Plu) was noted for the test item at the applied test concentrations. The observed stimulation index values were 1.2, 2.3 and 1.7 at test item concentrations of 10 %, 5 % and 2.5 % (w/v), respectively. No significant dose-response relationship was observed. Accordingly, the substance was considered to be not a skin sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A study according OECD TG 429 was performed to evaluate the skin sensitising potential of the test item. A formulation evaluation and a Dose Range Finding test (DRF) were performed to find an appropriate vehicle and the maximum applicable concentration according to the relevant guidelines. Solubility of the test item in vehicles preferred in the LLNA was evaluated and concentration series of 100 %, 50 %, 25 %, 10 % etc. were used. The maximum attainable concentration (based on solubility) was 10 % (w/v) in aqueous 1 % (w/v) Pluronic®PE 9200 (Plu). According to results of the DRF, where no adverse effect was observed up to this maximum concentration, the test item was examined in the main test as 10 %, 5 % or 2.5 % (w/v) formulations in the selected vehicle of Plu. Appropriate positive control (alpha-Hexylcinnamaldehyde, HCA), furthermore two negative control groups dosed with the vehicles of the test and positive control groups, respectively, were employed. The positive control item (25 % (w/v) HCA in Acetone:Olive oil 4:1 (v/v) mixture, AOO) induced significant stimulation over the relevant control (SI = 6.7) thus confirming the validity of the assay. No mortality was observed during the main test. No significant, treatment related effect on body weights or any other sign of systemic toxicity were observed in any treatment group. No signs of irritation (monitored by erythema scoring) or any other local effect were observed at the treatment site (ears) in any treatment group. No significantly increased lymphoproliferation (indicated by an SI ≥ 3) compared to the relevant control (Plu) was noted for the test item at the applied test concentrations. The observed stimulation index values were 1.2, 2.3 and 1.7 at test item concentrations of 10 %, 5 % and 2.5 % (w/v), respectively. No significant dose-response relationship was observed. Accordingly, the substance was considered to be not a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for skin sensitisation under Regulation (EC) No 1272/2008, as amended for the fifteenth time in Regulation (EU) 2020/1182.