2-(hydroxymethylamino)ethanol

Endpoint summary

Description of key information

The skin sensitization potential of 2-[hydroxy(methyl)amino]ethanol(34375-28-5) was estimatedby SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-[hydroxy(methyl)amino]ethanol(34375-28-5)was predicted to be sensitizing to the skin of female Pirbright-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3 with logKow as the primary descriptor.

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Not specified.

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 6-9 weeks
- Weight at study initiation: 344-485 g
- Housing: single housing makrolon cage, type III
- Diet: standard diet ad libitum (ALTROMIN(R) Nr. 3022 from Altromin, Lage, Germany)
- Water: ad libitum- Acclimation period: 7 daysENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2°C
- Humidity (%): 55 +/- 15 %
- Photoperiod (hrs dark / hrs light): 12 hrs / 12 hrs

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Concentration / amount:

Induction: Intrademal 30 %Epidermal: paste (0.5 g test substance with 0.4 ml physiol.

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

50%

Day(s)/duration:

48 hour

No. of animals per dose:

control group: 10
test group: 20

Details on study design:

MAIN STUDYA. I
NDUCTION EXPOSURE
Intradermal
- No. of exposures: 6 (2 x test substance, 2 x test substance / FCA (1:1), 2x FCA)
- Exposure period: Day 1
- Test groups: test group: see above
- Control group: same treatment, but vehicle instead of test substance
- Site: shoulder region
- Frequency of applications: once on day 1
- Duration: single exposure, next exposure on day 8
- Concentrations: 30 %Epidermal
- No. of exposures: 1
- Exposure period: Day 8-
Test groups: occlusive patch with test substance: paste (0.5 g test substance with 0.4 ml physiol. saline)
- Control group: same treatment, but vehicle instead of test substance
- Site: shoulder region
- Frequency of applications: once on day 8
- Duration: 48 h
- Concentrations: paste (0.5 g test substance with 0.4 ml physiol. saline)

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: day 22, day 23
- Exposure period: 24 h
- Test groups: right flank (vehicle), left flank (test substance)
- Control group: same as test group- Site: flank
- Concentrations: 50 %
- Evaluation (hr after challenge): 48 hrs after last challenge

Challenge controls:

yes

Positive control substance(s):

no

Statistics:

No data available.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

15

Total no. in group:

20

Clinical observations:

Skin sensitization effect were observed.

Remarks on result:

positive indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "S M W N"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and "h" )  and ("i" and "j" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alcohol OR N-Hydroxylamine derivatives by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol OR N-Hydroxylamine derivatives OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Amino, aliphatic attach [-N<] OR Hydroxy, aliphatic attach [-OH] OR Hydroxy, nitrogen attach [-OH] OR Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol OR Hydroxy compound OR Hydroxylamine OR Primary alcohol by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Alkylalkanol-amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "h"

Similarity boundary:Target: CN(O)CCO
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.16

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.8

Interpretation of results:

other: Sensitizing .

Conclusions:

The skin sensitization potential of 2-[hydroxy(methyl)amino]ethanol(34375-28-5) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-[hydroxy(methyl)amino]ethanol(34375-28-5)was predicted to be sensitizing to the skin of female Pirbright-Hartley guinea pig.

Executive summary:

The skin sensitization potential of 2-[hydroxy(methyl)amino]ethanol(34375-28-5) was estimatedby SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-[hydroxy(methyl)amino]ethanol(34375-28-5)was predicted to be sensitizing to the skin of female Pirbright-Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitization 

In different studies, 2-[hydroxy(methyl)amino]ethanol(34375-28-5)has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and human for target chemical2-[hydroxy(methyl)amino]ethanol(34375-28-5) .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of target chemical.

The skin sensitization potential of 2-[hydroxy(methyl)amino]ethanol(34375-28-5) was estimatedby SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-[hydroxy(methyl)amino]ethanol(34375-28-5)was predicted to be sensitizing to the skin of female Pirbright-Hartley guinea pig.

  It is supported by experimental study conducted by SHIRO TANAKA et al.(Contact Dermatitis, 1984) to evaluate the skin sensitizing potential of target substance 2-[hydroxyl (methyl)amino] ethanol (34375-28-5) in Human. Skin sensitization test for 2[(hydroxymethyl)amino]ethanol (34375-28-5) was assessed for its possible contact allergenic potential .For this purpose11 paperhangers (ages from 31 to 59; median 49 years old) were patch tested for the additives, 2-[(hydroxymethyl)amino ]ethanol and polyethylene glycol monolauroyl ester. They were observed for skin reactions after 48 and 72hours. The test material was patch tested at concentration of 5%.When pretested on 6 control subjects, these patch test solutions produced negative reactions. 2-[(hydroxymethyl) amino ] ethanol was the most allergenic to the patients after 72 hours observationIt can be concluded that2[(hydroxymethyl)amino]ethanol (34375-28-5)is a strong skin sensitizer in human .

 

Thus based on the above predictions on 2-[hydroxy(methyl)amino]ethanol(34375-28-5)andapplying weight of evidence, it can be concluded that2-[hydroxy(methyl)amino]ethanol is a strong skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 2-[hydroxy(methyl)amino]ethanol(34375-28-5)can be considered as “classified” for skin sensitization.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, 2-[hydroxy(methyl)amino]ethanol(34375-28-5)can be considered as “classified” for skin sensitization.