Reaction mass of Trisodium tris(D-gluconato(2-)-κO1,κO2)ferrate(3-) and Sodium chloride

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well conducted study according to GLP

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See section13

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

10%, 25%, 50%

No. of animals per dose:

6

Details on study design:

RANGE FINDING TESTS:
In order to determine the dose levels, a preliminary dose-range-finding study was conducted in 2 animals per dose level. Seven (7) concentrations of 0.5, 1, 2.5, 5, 10, 25 and 50% of FeNaEDTA in acetone/olive oil (3+1 v/v) and a negative control were examined. No sensitising potential could be
observed.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: The so-called stimulation (or LLN-) indices were calculated by dividing the average lymph node cell
counts or ear weights (punch biopsies) per group of the test item treated animals by the vehicle treated ones. Thus, in case of no stimulating effect
the index for the lymph node cell count is always below 1.4, for the ear weights 1.1 (cut-off values). Indices above 1.4 or 1.1, respectively, are
considered positive. A possible dose-relationship between the test item groups regarding the lymph node weights would have been examined by
linear regression analysis employing PEARSON's correlation coefficient. A significant dose-relationship of lypmph node weights is considered
positive. In addition, the average ear thickness per group was compared to the vehicle control group.

TREATMENT PREPARATION AND ADMINISTRATION:

Positive control substance(s):

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

Statistics:

U-test according to MANN and WHITNEY

Key result

Parameter:

SI

Value:

1.1

Test group / Remarks:

10%

Key result

Parameter:

SI

Value:

1.2

Test group / Remarks:

25%

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

50%

Parameter	Group 1, negative control	Group 2, 10%	Group 3, 25%	Group 4, 50%	Group 5, positive control
Cell count	1.000	1.098	1.170	1.045	1.461
Lymph node weight	1.000	1.034	1.138	1.172	1.517
Ear weight	1.000	1.037	1.043	1.049	1.238
Difference of ear thickness	1.000	1.070	1.113	1.116	1.135

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Under the conditions of this test, EDTA-FeNa was not considered to be a skin sensitizer.

Executive summary:

In a local lymph node assay according to OECD guideline 426 the skin senitisation potential of NaFeEDTA was evaluated.

Three concentrations of FeNaEDTA (10%, 25% and 50%, w/w) dissolved in acetone/olive oil (4:1 v/v) were tested in six female CBA mice per group and compared to a vehicle control group. In addition, a positive control group (30% solution v/v of hexyl cinnamic aldehyde in acetone/olive oil (4:1 v/v)) was employed. Open application of 25 μL of the appropriate dilution of the test item, the vehicle alone or the positive control (as appropriate) were administered to the dorsum of each ear on 3 consecutive days. On test day 4 lymph node cell count, ear weight (punch biopsies), ear swelling and weight of the lymph nodes were measured.

The positive control group caused the expected increases in lymph node cell count and ear weights (statistically significant at p ≤ 0.01). The values for the stimulation index of lymph node cell count and ear weight were 1.5 and 1.2, respectively.

Treatment with FeNaEDTA at concentrations of 10%, 25% or 50% (w/w) did not reveal any statistically significant increased values (p ≤ 0.01) for the lymph node cell counts and ear weights. The stimulation index of the lymph node cell count did not exceed the threshold level of 1.4, whereas the stimulation index of ear weights did not exceed the threshold level of 1.1. The slight increase of the lymph node weight in the 10%, 25% and 50% (w/w) test item treated groups is regarded as spontaneous, as no statistical significance was noted and the weights obtained are within the normal range observed for control animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Well performed GLP studies.

Respiratory sensitisation

Endpoint conclusion

Additional information:

As there is no skin sensitisation observed for the read across substances, it is concluded that also respiratory sensitisation potential is lacking.

Justification for classification or non-classification

Based on the data available there is no need to classify for skin or respiratory sensitisation according to GHS.