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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
10 May to 10 June 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP; on related material

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): trisodium EDDS (under code)
- Molecular formula (if other than submission substance): C10-H13-N2-O8. 3Na
- Molecular weight (if other than submission substance): 358
- Smiles notation (if other than submission substance): [Na+].[Na+].[Na+].OC(=O)[C@H](CC([O-])=O)NCCNC(CC([O-])=O)C([O-])=O
- Substance type: technical product
- Physical state: white powder
- Purity test date: no data
- Lot/batch No.: 02
- Expiration date of the lot/batch: 1 January 1998
- Stability under test conditions: stable in water
- Storage condition of test material: stored dry at room temperature, in dark

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: albino Himalayan spotted
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wolferstrasse 4, CH-4414 Fuellinsdorf, Switzerland
- Age at study initiation: 7-9 weeks
- Weight at study initiation: males, 473-565 g; females, 473-529 g
- Housing: individually in Makrolon cages on softwood bedding
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum (with 1 g/litre ascorbic acid added once weekly)
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
bi-distilled
Concentration / amount:
50%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
bi-distilled
Concentration / amount:
50%
No. of animals per dose:
10/sex/dose treated with test substance
5/sex/dose control group
Details on study design:
RANGE FINDING TESTS:
Induction: 2 animals of each sex were patch-tested with 5, 10, 20 and 50% of the test substance on four separate areas of the clipped skin for a 6-h exposure period.
Challenge: 2 animals of each sex were induced with 50% of the test substance and challenged with 5, 10, 20 and 50% on four separate areas of the clipped skin for a 6-h exposure period.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 10 males and 10 females
- Control group: 5 males and 5 females
- Site: shoulder region
- Frequency of applications: every 7 days
- Duration: 6 h
- Concentration: 0 (control) or 50%


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after last induction exposure
- Exposure period: 6 h
- Test groups: 10 males and 10 females
- Control group: 5 males and 5 females
- Site: on area of shoulder below that used for induction
- Concentrations: 50%
- Evaluation (h after challenge): 24 and 48 h after removal of the patch


OTHER: animals were observed for signs of clinical toxicity and body weights were recorded at start of acclimatization period, on day 1 of induction and at study termination
Challenge controls:
Negative controls (5/sex) received the challenge dose without previous induction exposure
Positive control substance(s):
no
Remarks:
Formaldehyde had been used in a separate test (25 November to 30 December 1992) to evaluate the incidence of allergic reactions in the guinea pig strain

Study design: in vivo (LLNA)

Statistics:
not applicable, no positive reactions were observed

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No evidence of local or systemic toxicity, no treatment-related deaths and no differences in body weight gain between the groups
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No evidence of local or systemic toxicity, no treatment-related deaths and no differences in body weight gain between the groups.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No evidence of local or systemic toxicity, no treatment-related deaths and no differences in body weight gain between the groups
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No evidence of local or systemic toxicity, no treatment-related deaths and no differences in body weight gain between the groups.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No evidence of local or systemic toxicity, no treatment-related deaths and no differences in body weight gain between the groups
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No evidence of local or systemic toxicity, no treatment-related deaths and no differences in body weight gain between the groups.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No evidence of local or systemic toxicity, no treatment-related deaths and no differences in body weight gain between the groups
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No evidence of local or systemic toxicity, no treatment-related deaths and no differences in body weight gain between the groups.

Any other information on results incl. tables

No evidence of erythema or edema was observed after each of the three induction exposures or at 24 or 48 h following the challenge dose.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
In a GLP study conducted according to OECD Guideline 406 and EU Method B.6, trisodium EDDS showed no sensitising potential to the clipped skin of guinea pigs after induction by three weekly exposures to 50% of the test material followed two weeks later by a 50% challenge dose (modified Buehler method).
Executive summary:
In a GLP study conducted according to OECD Guideline 406 and EU method B.6, trisodium EDDS was assessed for its sensitisation potential when applied to the skin of albino guinea pigs (modified Buehler method).

After a range-finding study to determine the concentrations of the test substance to use, groups of ten guinea pigs of each sex were exposed to a 50% solution of the test substance for 6 h under an occluded patch applied to the clipped shoulder region, followed by two further exposures at 7-day intervals. After a 2-week recovery period, the animals were exposed to a 50% challenge dose and observed for skin reactions for 48 h. Groups of five animals of each sex were used as negative controls, receiving only the challenge dose.

There was no evidence of positive skin reactions either after the induction exposures or after the challenge dose in any of the animals. No deaths occurred during the study and no clinical signs of toxicity or effects on body weight gain were seen.

In a modified Buehler assay, trisodium EDDS showed no sensitising potential to the skin of guinea pigs after induction by three weekly exposures to 50% of the test material followed two weeks later by a 50% challenge dose. According to EU CLP and DSD regulations, trisodium EDDS would not be classified as a skin sensitiser under the conditions of this test.

[Data on trisodium EDDS is considered relevant to use for understanding the sensitisation potential of EDDS acid, and is acceptable for using as read-across information.]