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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
March 09 to June 06, 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
This IUCLID for dimethyl adipate is compiled using data from the substance itself, a structuraly related compound (dimethyl glutarate) and a mixture of dibasic esters (dimethyl adipate, succinate and glutarate). The toxicity of each of these susbtances is similar and the document attached justifies why data on the category members can be used to support the data gaps for dimethyl adipate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
See information in the field "Confidential details on test material"

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, NL-5960 AD Horst, The Netherlands
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 16-24 g
- Housing:cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:under test conditions

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0.0% (control), 5, 10, 25, 50, 100% (w/v)
No. of animals per dose:
4 female animals per dose
Details on study design:
RANGE FINDING TESTS:
- Lymph node proliferation response: at 10, 25,50 and 100% (w/v)
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
As positive control for the current LLNA test, three groups each of four female mice were treated daily with alpha-hexylcinnamaldehyde at concentrations of 5 %, 10 % and 25 % (w/v) in acetone:olive oil, 4:1 (v/v) by topical application to the dorsum of each ear lobe (left and right) for three consecutive days. A control group of four mice was treated with the vehicle (acetone:olive oil, 4:1 (v/v).

The results obtained (STIMULATION INDEX (S.I.) for this positive test are reported as follows:.

Group 2 5* % (w/v) 2.4 * (S.I.)
Group 3 10 * % (w/v) 3.6 * (S.I.)
Group 4 25 % (w/v) 11.2 (S.I.)

A clear dose-response relationship was observed. * This value was used in calculation of EC3. The estimated concentration of test item required to produce a S.I. of 3 is referred to as the EC3 value and found to be EC3 = 7.5 % (w/v),

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
0.6
Test group / Remarks:
Test item concentration 5%
Key result
Parameter:
SI
Value:
0.6
Test group / Remarks:
Test item concentration 10%
Key result
Parameter:
SI
Value:
1
Test group / Remarks:
Test item concentration 25%
Key result
Parameter:
SI
Value:
0.6
Test group / Remarks:
Test item concentration 50%
Parameter:
SI
Value:
0.5
Test group / Remarks:
Test item concentration 100%
Key result
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: 4'890 minimum; 2'589 maximum;

Any other information on results incl. tables

The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured on a 13-scintillation counter See in text table below for stimulation index (S.I

Test item concentration

% (w/v)

S.I.

Group 2

5

0.6

Group 3

10

0.6

Group 4

25

1.0

Group 5

50

0.6

Group 6

100 (undiluted)

0.5

No dose-response relationship was observed.

Calculation of the EC 3 value was not performed because no test concentrations produced a STIMULATION INDEX (S.I.) of 3 or higher.

The radioactive disintegration values for the individual treatment groups are included in Table 1 below.

Viability / Mortality

No deaths occurred during the study period.

Clinical Signs

No clinical signs were observed in any animals of the control group, Group 2 (5 %), Group 3 (10 %) or Group 4 (25 %). On the second application day, a slight to moderate ear erythema was observed at both dosing sites in all mice of Group 5 (50 %) and Group 6 (100 %,  undiluted), persisting for a total of two days. The individual clinical were graded in severity of the symptoms into four grades: slight (1), moderate (2), severe (3) and very severe (4),.

Body weights

The body weight of the animals, recorded prior to the first application and prior to necropsy, was within the range commonly recorded for animals of the strain and age.

Table 1

Test item

Measurement

Calculation

Result

concentration

dpm

dpm -

number of

dpm per

S.I.

% (w/v)

BGa)

lymph nodes

lymph nodeb)

--

BG I

10

--

--

--

--

--

BGII

14

--

--

--

--

--

CG 1

4902

4890

8

611

--

5

TG 2

2978

2966

8

371

0.6

10

TG 3

2898

2886

8

361

0.6

25

TG4

4846

4834

8

604

1.0

50

TG5

2726

2714

8 **

339

0.6

100 *

TG6

2601

2589

8 **

324

0.5

*, undiluted as delivered by sponsor;

**, the size of the draining lymph nodes of this group was obviously small compared to those of the control group;

BG, background (1 ml 5% trichloroacetic acid) in duplicate;

CG, control group;

TG, test group;

S.I., simulation index

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the STIMULATION INDEX (S.I.). RHODIASOLV RPDE was found to be a non-sensitizer when tested at up to the concentration of 100 % (undiluted).

Executive summary:

In order to study a possible contact allergenic potential of RHODIASOLV RPDE,  a local lymph node assay (LLNA) was performed according to the OECD Guideline 429 and und GLP Regulations. Five groups each of four female mice were treated daily with the test item at concentrations of 5 %, 10 %, 25 %, 50 % (w/v) in acetone/olive oil (4/1, v/v) and 100 % (undiluted) by topical application to the dorsum of each ear lobe (left and right) for three consecutive days. A control group of four mice was treated with the vehicle (acetone/olive oil (4/1, v/v)) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine 3H-methyl thymidine. Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured. All treated animals survived the scheduled study period. No clinical signs were observed in any animals of the control group, Group 2 (5 %), Group 3 (10 %) or Group 4 (25 %). On the second application day, a slight to moderate ear erythema was observed at both dosing sites in all mice of Group 5 (50 %) and Group 6 (100 %, undiluted), persisting for a total of two days. The results obtained (Stimulation Index (S.I.)) for each group of animals and exposure were as follows: group 2 (5% (w/v)), S.I. 0.6; group 3 (10% (w/v)), S.I. 0.6; group 4 (25% (w/v)), S.I. 1.0; group 5 (50% (w/v)), S.I.  0.6; group 6 (100% (w/v)), S.I. 0.5. A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the stimulation index (S.I.). In this study S.I. of 0.6, 0.6, 1.0, 0.6 and 0.5 were determined with the test item at concentrations of 5 %, 10 %, 25 %, 50 % (w/v) in acetone/olive oil (4/1, v/v) and 100 % (undiluted), respectively.

RHODIASOLV RPDE was therefore found to be a non-sensitizer when tested at up to the concentration of 100 % (i.e., undiluted).