Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it was conducted similar to OECD Test Guideline 406.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The first-choice method according to REACH Annex VII §8.3, the Murine Local Lymph Node Assay, is known to give false positive results with hydrocarbon substances.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
RAEs are not expected to be more hazardous than DAE; therefore, read across to DAEs represents a conservative approach.

- Name of test material (as cited in study report): API 83-16, CAS No. 64742-05-8
- Physical state: Liquid, amber

- Viscosity, SSU: 67.2 at 100°F
- API Gravity: 16.7
- Flash Point: (°F) 335
- Pour Point (°F): 20
- Aniline Point (°F): 95.5
- Sulfur, Wt %: 2.64

- Composition of test material ASTM D-2007, Wt. %:
Saturates: 29.2
Aromatics 68.6

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver, Pennsylvania
- Age at study initiation: 5 to 6 weeks old
- Weight at study initiation: 435 to 598 grams
- Housing: individual cages
- Diet (e.g. ad libitum): Purina certified guinea pig chow 5026, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 24
- Humidity (%): 37 to 62
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 02/04/85 To: 03/15/85

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
50% v/v mixture in paraffin oil (sensitising application)
1% v/v mixture in paraffin oil (challenge dose)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
50% v/v mixture in paraffin oil (sensitising application)
1% v/v mixture in paraffin oil (challenge dose)
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: Consisted of eight guinea pigs, with each animal receiving 2 concentrations of test material. Originally administered undiluted and at 25%, 50%, and 75% v/v/ in paraffin oil. Because of irritation at the 25% level, additional concentrations of 10% v/v and 1% v/v were needed to determine irritation threshold. No dermal irritation resulted from the 1% v/v applications. The 10% and 25% v/v applications produced very slight irritation responses. The 25%,50%, and 75% v/v applications produced very slight to well-defined responses. Based upon these results, the test material was administered as a 50% v/v/ mixture (mild to moderately irritating) in paraffin oil for the sensitising applications and as 1% v/v mixture (the highest non-irritating concentration) in paraffin oil for the challenge dose.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 10 guinea pigs
- Control group: paraffin oil administered undiluted (0.4mL)
- Site: back, left anterior quadrant of prepared site on back
- Frequency of applications: one application per week for 3 weeks
- Duration: 3 weeks
- Concentrations: 50% v/v in paraffin oil


B. CHALLENGE EXPOSURE
- No. of exposures: single exposure
- Day(s) of challenge: two weeks (14 days)
- Exposure period: 6 hours
- Test groups: same 10 animals that received induction dose
- Control group: dosed with test material in the same manner
- Site: right anterior quadrant of prepared site on back
- Concentrations: 1% v/v in paraffin oil
- Evaluation (hr after challenge): 24 hours after, 3 hours prior to the 24-hour examination, the test site of each animal was depilated for 20 minutes and washed with lukewarm water


Challenge controls:
10 animals (previously untreated) were dosed with the test material mixture in the same manner as the test group.
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene

Results and discussion

Positive control results:
The erythema and oedema scores during the sensitising phase ranged from 1.7 to 2.0 and 1.0 to 1.8, respectively. The erythema and oedema scores for the challenge phase are 1.0 to 2.5 and 0 to 1.5, respectively.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1% v/v
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
oedema scores were all 0.0, erythema scores ranged from 0.0 to 1.0
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% v/v. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: oedema scores were all 0.0, erythema scores ranged from 0.0 to 1.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1% v/v
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
oedema scores are all 0.0, erythema scores ranged from 0.0 to 1.0
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1% v/v. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: oedema scores are all 0.0, erythema scores ranged from 0.0 to 1.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% v/v
No. with + reactions:
20
Total no. in group:
20

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Based upon the similar results obtained from the challenge phase and the naive control, light paraffinic distillate solvent extract is not sensitising to guinea pig skin according to EU criteria.
Executive summary:

Justification for Read Across

For purposes of classification and labelling and registration under REACH, aromatic extracts are sub-divided into the categories of distillate aromatic extracts (DAE), treated distillate aromatic extracts (TDAE), and residual aromatic extracts (RAE). Some of the classifications are based on 3-7 ring PAC content, which is not substantively affected by whether the aromatic extract is derived from paraffinic or naphthenic or “light” or “heavy” crude. Therefore, DAEs and RAEs are not subclassified based on crude oil source or viscosity. For most health endpoints, data from any one of the DAEs can be “read-across” to the remaining DAEs and whole RAE category. 

In a dermal sensitisation study using light paraffinic distillate solvent extract in paraffin oil, 5 to 6 week old Hartley guinea pigs were tested in a Buehler test which is similar to OECD test guideline 406. 10 test guinea pigs were dosed with 0.4 mL 50% v/v in paraffin oil for 3 weeks (1 dose/week) and then a challenge dose of 0.4 mL 1% v/v in paraffin oil 2 weeks after the last test dose. A naïve control group of 10 animals remained untreated during induction, but received the same dose as the test animals during the challenge phase.

 

A very slight erythema reaction was exhibited by 8 animals in the test group. These reactions did not exceed the highest reaction of the naïve control animals. The other two test animals exhibited no reaction. Based upon the similar results obtained from the challenge phase and the naive control, light paraffinic distillate solvent extract is not sensitising to guinea pig skin according to EU criteria. 

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because it was conducted similar to OECD Test Guideline 406.