Registration Dossier

Administrative data

Description of key information

One study with reliability 2 is available. Based on this study, no positive reaction was observed in animals treated with paradimethoxybenzene.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No standard Draize test. Study not GLP, and no data on vehicle used.
Principles of method if other than guideline:
Modified Draize test.
GLP compliance:
not specified
Type of study:
Draize test
Justification for non-LLNA method:
Study conducted prior to the recognition of the LLNA method as the preferred test method.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Own colony of Unilever laboratory
- Age at study initiation: no data
- Weight at study initiation: 350 g
- Housing: in wire mesh cages in pair by sex
- Diet: guinea pig diet, cabbage and hay ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data
Route:
intradermal
Vehicle:
no data
Concentration / amount:
no data
Route:
intradermal and epicutaneous
Vehicle:
no data
Concentration / amount:
no data
No. of animals per dose:
5 males and 5 females
Details on study design:
RANGE FINDING TESTS:
A preliminary study determined the ICC (injection challenge concentration), giving slight but perceptible irritation with no
oedema, 4 animals weighing 450 g (same sex) 0.1 ml injection intradermally, 0.1 ml of range of concentrations in solvent, examination of erythema
and oedema 24 h later.
The ACC (application challenge concentration), the highest concentration which caused no irritation. 4 animals weighing 450 g, 0.1 ml of
concentrations in solvent, applied 24 hours.

MAIN STUDY
A. INDUCTION EXPOSURE/DAY 0
- No. of exposures: 1
- SLS application: no
- Test groups: Test substance
- Control group: no
- Site: between the 2 auxillary and 2 inguinal lymph nodes
- Frequency of applications: 1 application in 4 intradermal injections.
- Duration: 14 days, day 0 to day 14
- Concentrations: 3%

Intradermal injection / day 0: administration onto 10 animals of 0.1 ml of the test substance at 3% by intradermal injection in 4 sites which overlie
the 2 auxillary and 2 inguinal lymph nodes.

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 14
- Test groups: ex: Test substance
- Control group: no
- Duration: 1 day
>Intradermal injection / day 14:
- Site: one flank
- Concentration: 0.2%(=ICC, Injection Challenge Control)
- exposure period: time of application
- Evaluation (hr after challenge): 24 h
0.1 ml of test substance was intradermally injected in one flank.

> Topical application / day 14:
- Site: the other flank
- Concentration: 50%(=ACC, Application Challenge Concentration)
0.1 ml of test substance was spread onto shaved flank in a small circular area which was not covered.
- exposure period: time of application
- Evaluation (hr after challenge): 24 h
24 hours after the challenge exposure, the reactions were scored and apparent sensitization reactions confirmed 7 days later by second challenge.

C. INDUCTION AND CHALLENGE REPEATED
INDUCTION EXPOSURE/DAY 21
- No. of exposures: 1
- SLS application: no
- Test groups: Test substance
- Control group: no
- Site: between the 2 auxillary and 2 inguinal lymph nodes
- Frequency of applications: 1 application in 4 intradermal injections.
- Duration: 14 days, day 21 to day 35
- Concentrations: 3%
Intradermal injections at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes of 10 animals with test substance at concentration of 3%.

CHALLENGE / DAY 35
- No. of exposures: 2
- Day of challenge: 35
- Test groups: Test substance
- Control group: no

* Intradermal injection / day 35
- Site: one flank
- Concentration: 0.2%(=ICC, Injection Challenge Control)
- exposure period: time of application
- Evaluation (hr after challenge): 24 h
0.1 ml of test substance was intradermally injected in one flank.

* Topical application / day 35
- Site: the other flank
- Concentration: 50%(=ACC, Application Challenge Concentration)
0.1 ml of test substance was spread onto shaved flank in a small circular area which was not covered.
- exposure period: time of application
- Evaluation (hr after challenge): 24 h

D. RECHALLENGE / DAY 42
- No. of exposures: 2
- Day of challenge: 42
- Test groups: Test substance
- Control group: yes, 4 previously untreated animals.

* Intradermal injection / day 42
- Site: one flank
- Concentration: 0.2%(=ICC, Injection Challenge Control)
- exposure period: time of application
- Evaluation (hr after challenge): 24 h
0.1 ml of test substance was intradermally injected in one flank.

* Topical application / day 42
- Site: the other flank
- Concentration: 50%(=ACC, Application Challenge Concentration)
0.1 ml of test substance was spread onto shaved flank in a small circular area which was not covered.
- exposure period: time of application
- Evaluation (hr after challenge): 24 h
Challenge controls:
no
Positive control substance(s):
no
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
0.1 ml at 50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 ml at 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
rechallenge
Group:
negative control
Dose level:
no data
Remarks on result:
other: No data
Reading:
rechallenge
Group:
positive control
Dose level:
no data
Remarks on result:
other: No data
Interpretation of results:
GHS criteria not met
Conclusions:
According to UN and EU GHS criterias, the substance is not classified for skin sensitization.
Executive summary:

In a dermal sensitization study (Sharp, 1978) with Paradimethoxybenzene, males and females Hartley guinea pigs  (5/sex) were tested in a modified Draize test. A 0.1 ml aliquot of test material, at 2.5 times the ICC, was injected intradermally at 4 sites which overlie the 2 auxiliary and 2 inguinal lymph nodes. The guinea pigs were challenged 14 days later by an intradermal injection of 0.1 ml test material into one flank and a topical open application of test material on the other flank at the respective injection challenge concentration (ICC) and application challenge concentration (ACC). Reactions were scored 24 hours after challenge treatments.

In absence of sensitization reactions, second induction and challenge procedures were repeated and a confirmatory challenge with controls was included. At each challenge with controls, 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively. Reactions were examined under a Philips colour-matching unit. Each injection was given a total score based on size (2 largest diameters), erythema and oedema. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. 

No positive reaction were observed. In this study, Paradimethoxybenzene is not a skin sensitizer.

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

Only one study, a Draize test on guinea pigs, was available. It was with validity 2 and was selected as key study.

In thisdermal sensitization study (Sharp, 1978) with Paradimethoxybenzene, males and females Hartley guinea pigs  (5/sex) were tested in a modified Draize test. A 0.1 ml aliquot of test material, at 2.5 times the ICC, was injected intradermallyat 4sites which overlie the 2 auxiliary and 2 inguinal lymph nodes. The guinea pigs were challenged 14 days later by an intradermal injection of 0.1 ml test material into one flank and a topical open application of test material on the other flank at the respective injection challenge concentration (ICC) and application challenge concentration (ACC). Reactions were scored 24 hours after challenge treatments.

In absence of sensitization reactions, second induction and challenge procedures were repeated and a confirmatory challenge with controls was included. At each challenge with controls, 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively. Reactions were examined under a Philips colour-matching unit. Each injection was given a total score based on size (2 largest diameters), erythema and oedema. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. 

No positive reaction were observed.

In this study, Paradimethoxybenzene is not a skin sensitizer.

This result was confirmed in results on Human data (see section 7.10.4) on studies considered as validity 4 (only summaries available).


Migrated from Short description of key information:
Paradimethoxybenzene is not sensitizing on guinea pigs, in Draize test.

Justification for classification or non-classification

Based on the available studies, the substance is not a skin sensitizer and no classification is required according to UN and EU GHS criteria.