Disodium 2-hydroxyethyliminodi(acetate)

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD TG 406, EPA TG OPPTS 870.2600, EEC Method B.6, JMAFF Agchem Test Guidelines and in accordance with the Principles of Good Laboratory prcatice (GLP)

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Agchem Test Guidelines

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The study was done before in 2002 before the LLNA became the required test method

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Hilltop Lan Animals Inc., Scottdale, PA
- Age at study initiation: young adults approximately 8 -9 weeks of age
- Weight at study initiation: males: 469-506 grams and females: 451-493 grams
- Housing: The animals were housed indivdually in suspended stainless steel cages.
- Diet (e.g. ad libitum): PMI certified guinea pig chow #5026 (Purina Mills, Inc.) was provided adlibitum to the animals throughout the study.
- Water (e.g. ad libitum): Municipal tap water treated by reverse osmosis was available ad libitum throughout the study.
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23 °C
- Humidity (%): 32-57%
- Air changes (per hr): 10-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100% undiluted test material

Route:

epicutaneous, open

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100% undiluted test material

No. of animals per dose:

10 male + 10 female

Details on study design:

RANGE FINDING TESTS: The range finding test was conducted at 100, 75, 50 and 25% w/v in deionised water administered topically to 4 guinea pigs (one animal/concentration). The four conentrations were applied to clipped area of each animal. Following chamber application, the trunk of each animal was wrapped with elatic wrap and secured with adhesive tape to prevent removal of the chambers and the animal returned to its cage. Approximately 6 hours after chamber application, the binding materials were removed. The test sites were then wiped with gauze moistened with deionized water followed by dry gauze to remove test material residue and animals returned to their cages. The test sites of these animals were graded for irritation at approximately 24 and 48 hours following chamber application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 (days 0, 7 and 13)
- Exposure period: 3 consecutive induction exposures
- Test groups: 1
- Control group: no control group
- Site: left back side of each animal
- Frequency of applications: once on days 0, 7 and 13
- Duration: once on days 0, 7 and 13
- Concentrations: A dose of 0.3 ml of the test material was placed on a 25 mm Hilltop chamber backed by adhesive tape (occlusive patch) and placed to the clipped surface.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 27
- Exposure period: 6 hours
- Test groups: 1
- Control group: 1
- Site: right back side of each animal
- Concentrations: 100% undiluted test material was used
- Evaluation (hr after challenge): 24 and 48 hours following chamber removal

Challenge controls:

A group of 5 male + 5 female guinea pigs served as challenge control

Positive control substance(s):

yes

Remarks:

1-Chloro-2,4-dinitrobenzene (DNCB) and alpha-Hexylcinnamaldehyde (HCA)

Positive control results:

Following induction at 0.1% w/v DNCB in acetone/ethanol and challenge at levels of 0.1% and 0.05% w/v DNCB in acetone/ethanol, a contact sensitization response was observed, thereby demonstrating the susceptibility of the test system to this sensitizing agent.
Following induction at 5% w/v HCA in ethanol and challenge at levels of 2.5% and 1% w/v HCA in acetone, a contact sensitization response was observed, thereby demonstrating the susceptibility of the test system to this sensitizing agent.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 % undiluted

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100% undiluted

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100% undiluted

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100% undiluted

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, XUS 40855.001 is not considered to be a contact skin sensitizer in guinea pigs.

Executive summary:

The dermal sensitization potential of XUS 40855.01, which contained 27% Na2HEIDA as the active ingredient, was evaluated in Hartley-derived albino guinea pigs. Ten male and ten female guinea pigs were topically treated with 100% XUS 40855.01, once per week, for three consecutive weeks.

Following a two-week rest period, a challenge was performed whereby the twenty test and ten previously untreated (naive) challenge control guinea pigs were topically treated with 100% XUS 40855.01. Challenge responses in the test animals were compared with those of the challenge control animals.

Following challenge with 100% XUS 40855.01, dermal scores of 0 were noted in all of the test and challenge control animals. Group mean dermal scores were noted to be 0.0 in the test and challenge control animals.

Following induction at 0.1% w/v DNCB (1-Chloro-2,4-dinitrobenzene) in acetone/ethanol and challenge at levels of 0.1% and 0.05% w/v DNCB in acetone/ethanol, a contact sensitization response was observed and following induction at 5% w/v HCA (á-Hexylcinnamaldehyde ) in ethanol and challenge at levels of 2.5% and 1% w/v HCA in acetone, a contact sensitization response was observed, thereby demonstrating the susceptibility of the test system to this sensitizing agent.

Based on the results of this study, XUS 40855.01 is not considered to be a contact sensitizer in guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A Buehler test conducted with both EDG-Na2 (Dow, 2002) and NTA-Na3 (BASF, 1997) in guinea pigs demonstrates a negative result. A non-irritating substance formulation (50% in water) was used for dermal inductions. According to OECD 406 mild to moderate skin irritation is the prerequisite for this method. If undiluted substance does not cause irritation, a negative result can be used for risk assessment. If a dilution is applied uncertainty remains whether or not undiluted substance would cause the adequate irritation and subsequent sensitization. However, the result suggests a lack of a strong skin sensitisation potential of NTA-Na3.

According to a DerekfW prediction for NTA-Na3 (cited in EU RAR draft 2008), the chemical reactivity and so the binding to proteins is limited. This prediction at its own is has limited weight, because negative findings usually have to be considered out of the applicability domain. However, viewing the alerts present in DerekfW this type of chemicals may be considered negative. Protein binding is considered limited, because the ester-salt is not activated and the amine is tertiary which may be sterically hindered. This conclusion is supported by a TOPKAT models. NTA is within the TOPKAT domain and provides an analogue which is negative. Despite the uncertainty due to a lack of mechanistic reasoning, the analogue approach can add to the overall impression that the chemical is not a sensitizer.

It is noted that also EDG-Na2 does not interact with protein, which is considered a requirement for sensitization (needed for haptenisation).The bioavailability is limited as dermal penetration is low. Finally, also decades of use of this substance did not result in any reports of people becoming sensitized.

Migrated from Short description of key information:

Data are available for EDG-Na2 and the structurally related substance NTA-Na3 (see also read across document in section 13).

Justification for selection of skin sensitisation endpoint:

A Buehler test did not show skin sensistising properties which was confirmed by negatibve tests with the structurally related substance NTA-Na3.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Because EDG-Na2 is not considered to be a skin sensitiser it is not expected that it would be a respiratory sensitiser as all respiratory sensitisers tested have shown skin sensitising properties in skin sensitisation tests.

Justification for classification or non-classification

Because EDG-Na2 is not considered to be a skin sensitiser no classification is needed for this endpoint.