Registration Dossier

Administrative data

Description of key information

The target substance 1,2-Benzenedicarboxylic acid, di-C8-10-alkyl esters was not sensitising in a study according to OECD 406.

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:
1990-09-10 to 1990-10-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test was performed before REACH enforcement.
Specific details on test material used for the study:
- Name of test material (as cited in study report): WITAMOL 118
- Substance type: product
- Physical state: liquid
- Stability under test conditions: not mentioned
- Storage condition of test material: below 40 °C, under nitrogen under a laboratory hood in the dark
- Other: none
Species:
guinea pig
Strain:
other: Dunkin Hartley, Pirbright White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 382-487 g
- Housing: 1 - 5 animals in Makrolon cages type IV
- Diet (e.g. ad libitum): G4 complete feed for guinea pigs ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 14 days (main test)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1
- Humidity (%): 40 - 77
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
- Concentrations used for induction: intradermal treatment: approx. 5 % in corn oil; dermal treatment: 100 %
- Concentration in Freunds Complete Adjuvant (FCA): approx. 5 % test substance in a mixture of FCA and corn oil (1:1)
- Concentrations used for challenge: 100 %
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
- Concentrations used for induction: intradermal treatment: approx. 5 % in corn oil; dermal treatment: 100 %
- Concentration in Freunds Complete Adjuvant (FCA): approx. 5 % test substance in a mixture of FCA and corn oil (1:1)
- Concentrations used for challenge: 100 %
No. of animals per dose:
test group: 20 animals
control group: 10 animals
Details on study design:
RANGE FINDING TESTS:
A dose range finding was performed in a preliminary study. 0.1 ml of test substance in corn oil (0, 0.1, 0.5, 1, 2.5, 5 and 10 g test substance/100 ml corn oil) were applied intracutaneously into the left side of two animals. 24 hours after application the skin reactions were assessed. For dermal applications undiluted test substance and concentrations of 10, 20 and 50 g test substance/100 ml corn oil were applied on patches of 2x2 cm to the clipped skin of 4 animals. The patches were removed after 24 hours and dermal reactions were read immediately, 24 and 48 hours after patch removal.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1st exposure: intracutaneous injections (0.1 cm³); 2nd exposure: epicutaneous for 48 hours; evaluation after 1 and 24 hours each
- Concentration in Freunds Complete Adjuvants (FCA): test substance in vehicle (5g/100 cm³) in a mixture of FCA and vehicle (1:1)
- Test group: dermal: 100 % test substance (2 x 4 cm patch)
- Control group: vehicle (2 x 4 cm patch)
- Frequency of applications: day 0: intradermal treatment, day 6: pretreatment with sodium dodecyl sulphate (10% in vaseline) and day 7: dermal treatment
- Duration: 3 weeks


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 21
- Exposure period: dermal application for 24 hours
- Test groups: test substance (2 x 2 cm patch)
- Control group: test substance (2 x 2 cm patch)
- Site: left flanks
- Concentrations: 100 %
- Evaluation: 24, 48 and 72 hours after application
Challenge controls:
see above B. Challenge exposure
Positive control substance(s):
not specified
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
1st reading
Group:
positive control
Remarks on result:
other: positive control performed once a year

RESULTS OF PILOT STUDY:

- intracutaneous application: well defined erythema and moderate edema at concentrations of 10 g test substance /100 ml corn oil. At concentrations of 0, 0.1, 0.5, 1, 2.5, 5 and 10 g test substance/100 ml corn oil very slight erythema and moderate edema were observed.

- dermal application: no skin reactions at any dose

RESULTS OF TEST

- Sensitization reaction: 0/20

- Clinical signs: no substance specific observations

Interpretation of results:
GHS criteria not met
Executive summary:

1,2-Benzenedicarboxylic acid, di-C8-10-alkyl esters was not sensitising in a study according to OECD 406.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because the available in vitro test methods are not applicable for the substance and therefore an in vivo skin sensitisation study was conducted
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitising effects of 1,2-Benzenedicarboxylic acid, di-C8-10-alkyl esters and structurally related phthalates was evaluated in animal experiments as well as a human repeat insult patch test (HRIP) with the undiluted substances. No skin sensitisation was observed.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

No evidence of skin sensitisation in animal tests as well as in a human volunteer HPRIT study were found. Hence the test substance is not classified according to Regulation (EC) No 1272/2008.