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Administrative data

Description of key information

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 (Arcelin, 1993c).

In a GLP study conducted according to a protocol similar to OECD Guideline 406, trisodium EDDS showed no sensitising potential when applied to the clipped skin of guinea pigs after induction by three weekly exposures to 100% (0.5 g) of the test material followed two and three weeks later by a 100% challenge dose (Merriman, 1995).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 May to 10 June 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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 OTS 798.4100 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
In vivo test undertaken prior to 2005
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., W¿lferstrasse 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
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
bi-distilled
Concentration / amount:
50%
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
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
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 chemical
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.
Reading:
1st reading
Group:
positive control
Remarks on result:
not measured/tested
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

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.

Interpretation of results:
GHS criteria not met
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 regulation, trisodium EDDS would not be classified as a skin sensitiser under the conditions of this test.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
20 December 1994 to 2 February 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Relative humidity was reportedly 23-64% (OECD Guideline recommends 30-70%; this deviation is considered to have no adverse effect on the outcome of this study)
GLP compliance:
yes
Type of study:
Buehler test
Species:
guinea pig
Strain:
other: Hartley-derived albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley Inc., Haslett, Michigan, USA
- Age at study initiation: "young adult"
- Weight at study initiation: males, 341-420 g; females, 309-379 g
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): purified tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 23-64 (OECD Guideline recommends 30-70%)
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Concentration of test material used for induction: Topical: 0.5 g neat in Hilltop chamber
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Concentration of test material used for induction: Topical: 0.5 g neat in Hilltop chamber

Concentration of test material used for each challenge: 0.5 g neat in Hilltop chamber
No. of animals per dose:
Number of animals in test group: 10/sex (1 male died on day 20 prior to the challenge phase)
Number of animals in negative control group: 5/sex
Number of animals in positive control group: 3/sex
Number of animals in postive, non-induced control group: 2/sex
Details on study design:
RANGE FINDING TESTS:
In an initial range-finding study, two animals of each sex were topically exposed to 50, 60, 80 and 100% of the test substance under four occluded patches or in Hilltop chambers for 6 h. All animals were found dead the next day, and clinical abnormalies suggested that test substance-related toxicity may have occurred.

In a second study, two animals of each sex were treated with 100% of the test substance under an occluded Hilltop chamber for 6 h.

To determine the appropriate challenge dose two animals of each sex were topically exposed to either 50 and 75% or 25 and 100% under occluded patches or Hilltop chambers for 6 h.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 10/sex. Test substance in Hilltop chamber (test site moistened with distilled water prior to application of test substance)
- Control group: 5/sex; no treatment
- Site: left shoulder area
- Frequency of applications: once per week for 3 weeks (days 0, 7 and 14)
- Duration: 3 weeks
- Concentrations: 100% (0.5 g as powder)

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: days 28 and 35
- Exposure period: 6 h
- Test groups: test substance in Hilltop chamber (test site moistened with distilled water prior to application of test substance)
- Control group: test substance in Hilltop chamber (test site moistened with distilled water prior to application of test substance)
- Site: right shoulder area
- Concentrations: 100% (0.5 g as powder)
- Evaluation (hr after challenge): 24 and 48 hr after patch removal


OTHER: observations for signs of clinical toxicity; body weights taken on day 1 for the test animals and on the day prior to the challenge phases for test animals and the negative and positive control animals
Challenge controls:
Five naive guinea pigs of each sex were exposed to the challenge dose of 0.5 g on day 28 of the study
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene, 0.5% in ethanol used for the induction phases, 0.1 and 0.2% used for the challenge. Control animals received only the challenge doses
Positive control results:
For erythema, the positive control scored grades of 1 in three animals and 2 in three animals at 24 h, and 1 in five animals and 2 in one animal at 48 h when exposed to 0.1%. The grades after exposure to 0.2% were 2 in two animals and 4 in four animals at both 24 and 48 h.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5 g
No. with + reactions:
1
Total no. in group:
19
Clinical observations:
slight but confined or moderate patchy erythema seen in one animal.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 g. No with. + reactions: 1.0. Total no. in groups: 19.0. Clinical observations: slight but confined or moderate patchy erythema seen in one animal..
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 g
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 g. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5 g
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 g. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 g
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 g. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 g
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.5 g. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 g
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5 g. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 g
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.5 g. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 g
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5 g. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 24 and 48 hr after challenge
Group:
positive control
Dose level:
0.1%
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
slight to moderate erythema, very slight to severe edema
Remarks on result:
other: Reading: other: 24 and 48 hr after challenge. Group: positive control. Dose level: 0.1%. No with. + reactions: 6.0. Total no. in groups: 6.0. Clinical observations: slight to moderate erythema, very slight to severe edema.
Reading:
other: 24 and 48 hr after challenge
Group:
positive control
Dose level:
0.2%
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
moderate to severe erythema, very slight to severe edema, blanching, mild eschar formation
Remarks on result:
other: see Remark
Remarks:
Reading: other: 24 and 48 hr after challenge. Group: positive control. Dose level: 0.2%. No with. + reactions: 6.0. Total no. in groups: 6.0. Clinical observations: moderate to severe erythema, very slight to severe edema, blanching, mild eschar formation.

Other observations: 8 out of 19 test animals showed slight patchy erythema at 24 h following the first challenge, and 15 animals showed a slight patchy erythema 24 h after the rechallenge.

 

9 out of 10 and 3 out of 10 negative control animals showed slight patchy erythema 24 hours after challenge and rechallenge respectively.

One animal in the treated group was found dead on day 20, the cause of which could not be determined. All other animals remained healthy and gained weight throughout the study.

Interpretation of results:
GHS criteria not met
Conclusions:
In a GLP study conducted according to a protocol similar to OECD Guideline 406, trisodium EDDS showed no sensitising potential when applied to the clipped skin of guinea pigs after induction by three weekly exposures to 100% (0.5 g) of the test material followed two and three weeks later by a 100% challenge dose (modified Buehler method).
Executive summary:

In a GLP study conducted according to a protocol similar to OECD Guideline 406, trisodium EDDS was assessed for its ability to induce skin sensitisation in a Buehler assay in albino guinea pigs.

After a range-finding study, ten animals of each sex were placed in Buehler restrainers and exposed to an induction dose of 0.5 g of trisodium EDDS in an occluded Hilltop chamber for 6 h. The induction process was repeated 7 and 14 d later. After a further 14 d the treated animals and an untreated control group (5/sex) received a challenge dose of 0.5 g for 6 h. The test sites were scored for erythema and edema 24 and 48 h after patch removal. The test sites were rechallenged 7 d later.

One animal in the treatment group showed slight confluent erythema 24 h after challenge application; all other animals in this group as well as the control group showed no reaction or slight patchy erythema at 24 and 48 h post challenge. The positive controls developed moderate to severe erythema demonstrating the validity of the study. One animal in the treatment group died on day 20 (prior to the challenge phase) from undetermined causes; all other animals remained healthy and gained in body weight throughout the study.

In conclusion, trisodium EDDS exhibited no evidence of a skin sensitising potential when tested at 100% (0.5 g) in a Buehler sensitisation assay in guinea pigs. According to EU CLP regulation, trisodium EDDS would not be classified as a skin sensitiser under the conditions of this test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

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). 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 (Arcelin, 1993c).

In a GLP study conducted according to a protocol similar to OECD Guideline 406, trisodium EDDS was assessed for its ability to induce skin sensitisation in albino guinea pigs (modified Buehler method). Groups of ten animals of each sex were placed in Buehler restrainers and exposed to an induction dose of 0.5 g of neat trisodium EDDS in an occluded Hilltop chamber for 6 h. The induction process was repeated 7 and 14 d later. After a further 14 d the treated animals and an untreated control group (5/sex) received a challenge dose of 0.5 g for 6 h. The test sites were scored for erythema and edema 24 and 48 h after patch removal. in addition, the test sites were rechallenged 7 d later. One animal in the treatment group showed slight confluent erythema 24-h after challenge application; all other animals in this group as well as the control group showed no reaction or slight patchy erythema at 24 and 48 h post challenge. The positive controls developed moderate to severe erythema demonstrating the validity of the study. One animal in the treatment group died on day 20 (prior to the challenge phase) from undetermined causes; all other animals remained healthy and gained in body weight throughout the study (Merriman, 1995).

In a GLP study, trisodium EDDS was assessed for its skin sensitising potential in a human repeat insult patch test. During the induction phase, a 5% solution was applied to the skin of the upper arm of more than 100 individuals for 24 h under an occluded patch on alternate working days over a three-week period (9 applications). Between 12-20 days after the last induction exposure, a challenge dose of 5% was applied under an occluded patch to the same area and as a control to a similar site on the other arm. The test areas were examined at 48 and 96 h after application of the challenge dose. No evidence of either irritation during the induction stage or of sensitisation after the challenge application was observed in any of the 111 individuals who completed the study (Rybicki, 1993).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no data relating to respiratory sensitisation in humans or laboratory animals. However, the lack of skin sensitisation potential in humans and guinea-pigs suggests that it would not possess the potential to cause such an effect.

Justification for classification or non-classification

According to EU CLP regulation, trisodium EDDS would not be classified as a skin or respiratory sensitiser under the conditions of the tests described