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Skin sensitisation

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Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1990-08-29 to 1992-03-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it was conducted according to EPA OTS 798.4100.
Justification for type of information:
Read across justification included in Section 13
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Qualifier:
equivalent or similar to guideline
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.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sasco, Inc., Omaha, Nebraska
- Age at study initiation: young adult
- Weight at study initiation: 300 to 500 grams
- Housing: individually housed in stainless steel, wire mesh bottom cages
- Diet: fresh Agway certified guinea pig feed provided ad libitum, throughout both acclimation and study periods
- Water: provided ad libitum via automatic watering system
- Acclimation period: 14 days for induction phase animals; 7 days for dose selections phase animals


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 26 degrees celsius
- Humidity (%): 40 to 70%
- Air changes (per hr): no less than ten changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark


IN-LIFE DATES: From: 1990-08-29 To: 1990-10-12
Route:
epicutaneous, occlusive
Vehicle:
other: Mineral oil
Concentration / amount:
Of test substance at:

Dose selection (irritation) phase: undiluted F-133, 1:2 v/v, 1:4 v/v, and 1:8 v/v F-133

Induction phase: undiluted

Challenge phase: 1:4 v/v
Route:
epicutaneous, occlusive
Vehicle:
other: Mineral oil
Concentration / amount:
Of test substance at:

Dose selection (irritation) phase: undiluted F-133, 1:2 v/v, 1:4 v/v, and 1:8 v/v F-133

Induction phase: undiluted

Challenge phase: 1:4 v/v
No. of animals per dose:
Of test substance at:

Dose selection phase: six animals

Induction phase and challenge phase: ten animals

Details on study design:
RANGE FINDING TESTS: Six guinea pigs were used for the dose selection phase. Each animal was dosed with either undiluted, or 1:2 v/v, 1:4 v/v,
or 1:8 v/v mineral oil dilutions. The respective dilutions were applied to four pads, placed on the shaved areas, and occlusively wrapped. the
wrappings were removed after six hours and the skin was scored using the Draize method after 24 hours.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three
- Exposure period: 6 hours
- Test groups: one group of ten guinea pigs dosed with 0.5 ml of undiluted F-133
- Control group: one group of 10 guinea pigs were dosed with 0.3% DNCB in 80% ethanol/water and served as the positive control;
one group of 4 guinea pigs were dosed with 0.5 mL of undiluted test substance to serve as the challenge control; one group of 4 guinea pigs
were dosed with mineral oil to serve as the vehicle control group
- Site: shaved strip of hair along one side of the dorsal midline
- Frequency of applications: one 6 hour exposure per week
- Duration: 3 weeks
- Concentrations: undiluted test article


B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: the challenge phase took place 14 days following the last induction application
- Exposure period: 6 hours
- Test groups: the induction/challenge group consists of 10 guinea pigs dosed with a 1:4 F-133 dilution of the test article
- Control group: four guinea pigs treated with 1:4 dilution of F-133 in mineral oil as challenge control, ten guinea pigs treated with 0.2% DNCB in 80% ethanol/water as induction/ challenge positive control, four guinea pigs treated with 0.2% DNCB in 80% ethanol/water as challenge control,
four guinea pigs in the mineral oil as vehicle control
- Site: shaved strip of hair along one side of the dorsal midline on the opposite side from the induction test site.
- Concentrations: 1:4 dilution of F-133
- Evaluation (hr after challenge): 24 and 48 hours after exposure


Challenge controls:
1:4 dilution of F-133 challenge control; 0.2% DNCB challenge control
Positive control substance(s):
yes
Remarks:
1,4 dinitrochlorobenzene (2,4 DNCB)
Positive control results:
DNCB induced an appropriate positive response in the induction and challenge phases and is considered a delayed contact sensitizer, under the conditions of this test.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1:4 dilution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Severity Index (erythema + oedema) = 0.0
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1:4 dilution. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Severity Index (erythema + oedema) = 0.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1:4 dilution
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
Severity Index (erythema + oedema) = 0.0
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1:4 dilution. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: Severity Index (erythema + oedema) = 0.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.2%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Severity Index (erythema + oedema) = 3.8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.2%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Severity Index (erythema + oedema) = 3.8.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1:4 dilution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Severity Index (erythema + oedema) = 0.0
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1:4 dilution. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Severity Index (erythema + oedema) = 0.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1:4 dilution
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
Severity Index (erythema + oedema) = 0.0
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1:4 dilution. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: Severity Index (erythema + oedema) = 0.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.2%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Severity Index (erythema + oedema) = 3.0
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.2%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Severity Index (erythema + oedema) = 3.0.

The scores after the challenge treatment are summarised below


Group

Time

Response Grade Range

Incidence

F-133 Induction/Challenge group

24 h

0

0/10

 

48 h

0

0/10

F-133 Challenge control

24 h

0

0/4

 

48 h

0

0/4

DNCB Induction/Challenge positive control

24 h

3-5

10/10

 

48 h

2-4

10/10

DNCB Challenge control

24 h

0-1

3/4

 

48 h

0-1

3/4

Vehicle control

24 h

0

0/4

 

48 h

0

0/4


On the basis of the above response, the test material was not sensitizing.

No. with positive reactions:

Induction Phase:

Treatment 1 Scores: 9 out of 10 (test group); dose: 0.5 ml of undiluted F-133

Treatment 1 Scores: 9 out of 10 (positive control); dose: 0.5 ml of 0.3% DNCB

Treatment 2 Scores: 10 out of 10 (test group); dose: 0.5 ml of undiluted F-133

Treatment 2 Scores: 10 out of 10 (positive control); dose: 0.5 ml of 0.3% DNCB

Treatment 3 Scores: 10 out of 10 (test group); dose: 0.5 ml of undiluted F-133

Treatment 3 Scores: 10 out of 10 (positive control); dose: 0.5 ml of 0.3% DNCB

Challenge Scores:

0 out of 10 (Induction/Challenge test group); dose: 0.5 ml of F-133 1:4 dilution in mineral oil

0 out of 4 (F-133 Challenge Control); dose: 0.5 ml of F-133 1:4 dilution in mineral oil

10 out of 10 (DNCB Induction/Challenge Group); dose: 0.5 ml of 0.3% DNCB in 80% ethanol

3 out of 4 (DNCB Challenge Control); dose: 0.5 ml of 0.2% DNCB in 80% ethanol

0 out of 4 (Vehicle Challenge Control); dose: 0.5 ml of mineral oil

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
During the challenge phase, exposure of a 1:4 dilution of thermocracked kerosine to induction phase test animals did not yield higher response grades, severity, or incidence than those associated with the naive challenge control group exposed to thermocracked kerosine.

During the challenge phase, exposure of 0.2% DNCB to induction phase positive control animals elicited significantly higher response grades, severity indices, and incidence over the naive DNCB challenge control group. This indicates an appropriate positive response.

The vehicle irritation control group was free of dermal irritation during the challenge phase therefore, mineral oil used as a dilutant is not an irritant.

Therefore, under the conditions of this study, F-133 is not considered a delayed contact sensitizer.
Executive summary:

In a dermal sensitisation study using thermocracked kerosine in mineral oil, male young adult Pig/Hartley guinea pigs were tested using a modified Buehler technique.

During the challenge phase, a second exposure of a 1:4 dilution of thermocracked kerosine to induction test animals did not yield higher response grades, severity, or incidence than those associated with the naive challenge control group exposed to thermocracked kerosine. During the challenge phase, exposure of 0.2% DNCB to induction positive control animals elicited significantly higher response grades, severity indices, and incidence over the naive DNCB challenge control group. The vehicle irritation control group was free of dermal irritation during the challenge phase. Therefore, under the conditions of this study, thermocracked kerosine is not considered a delayed contact sensitiser and DNCB induced an appropriate positive response.

This study received a Klimisch score of 1 and is classified as reliable without restriction because it was conducted according to EPA OTS 798.4100.

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

Data on related substances have been used to 'read-across' and predict the hazard properties. A 'read-across' justification document can be found in section 13.

 In the key dermal sensitisation study (Klimisch score=1; ARCO, 1992), thermocracked kerosine in mineral oil was tested on male young adult Pig/Hartley guinea pigs using a modified Buehler technique. During the challenge phase, a second exposure of a 1:4 dilution of thermocracked kerosine to induced test animals did not yield higher response grades, severity, or incidence than those associated with the naive challenge control group exposed to thermocracked kerosine. During the challenge phase, exposure of 0.2% DNCB to induction positive control animals elicited significantly higher response grades, severity indices, and incidence over the naive DNCB challenge control group. The vehicle irritation control group was free of dermal irritation during the challenge phase. Therefore, under the conditions of this study, thermocracked kerosine is not considered a delayed contact sensitiser and DNCB induced an appropriate positive response.

 

Migrated from Short description of key information:

A sample of hydrodesulphurised kerosine was not a skin sensitiser when tested in guinea pigs by the Buehler method

Respiratory sensitisation

Endpoint conclusion
Additional information:

This endpoint is not a REACH requirement.

Migrated from Short description of key information:

This endpoint is not a REACH requirement.

Justification for classification or non-classification

Kerosines are not considered skin sensitisers based on the information presented above. Therefore, kerosines do not meet the criteria for classification as a dermal sensitiser under EU CLP Regulation (EC No. 1272/2008).

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