Registration Dossier

Administrative data

Description of key information

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other: GLP compliant, guideline study, available as unpublished report, restrictions in design and reporting but otherwise adequate for assessment
Qualifier:
according to
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Deviations:
yes
Remarks:
only 10 animals in test group
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
Study conducted before LLNA guideline
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sasco Inc., Omaha, Nebraska, USA.
- Age at study initiation: Young adult
- Weight at study initiation: 300-500 g
- Housing: Individually in stainless steel, wire mesh bottom cages
- Diet: Agway guinea pig feed ad libitum
- Water: ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 64-79°F
- Humidity: 40-70%
- Air changes: At least 10/h
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: 7 February 1990 To: 16 March 1990
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
E000144700 - 1:2 v/v dilution for induction; 1:4 v/v dilution for challenge
DNCB (positive control) - 0.3% for induction; 0.2% for challenge
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
E000144700 - 1:2 v/v dilution for induction; 1:4 v/v dilution for challenge
DNCB (positive control) - 0.3% for induction; 0.2% for challenge
No. of animals per dose:
10 (test, positive control and vehicle control groups)
4 (challenge controls )
Details on study design:
RANGE FINDING TESTS: 6 guinea pigs exposed to neat, 1:2, 1:4 and 1:8 v/v dilutions in mineral oil. 0.5 mL applied for 6 hours and irritation assessed using the Draize scoring system approximately 24 and 48 hours after treatment. No irritation was seen at the 24 hour reading. At the 48 hour reading erythema and oedema were present at the neat site, oedema was present at the 1:2 dilution site and no signs of irritation were seen at the 1:4 and 1:8 v/v dilution sites. Dilutions of 1:2 and 1:4 for the induction and challenge applications, respectively, were selected for use in the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours, once per week
- Test groups: 0.5 mL of a 1:2 v/v dilution of E000144700 in mineral oil
- Control group: 0.5 mL of mineral oil
- Site: shaved dorsal area

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after last induction application
- Exposure period: 6 hours
- Test groups: 0.5 mL of a 1:4 v/v dilution of E000144700 in mineral oil
- Control group: 0.5 mL of a 1:4 v/v dilution of E000144700 in mineral oil
- Site: naive site on the shaved dorsal area
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
Unused naive guinea pigs were used to distinguish between "background" irritation and actual allergic response (4 guinea pigs for each group-test, vehicle control and positive control)
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene
Positive control results:
Response grades, severity and incidence following challenge exposure to DNCP resulted in a significantly higher response than that seen in the naive challenge control group.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1:4 v/v dilution
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1:4 v/v dilution. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: no response.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1:4 v/v dilution
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1:4 v/v dilution. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: no response.
Reading:
1st reading
Hours after challenge:
24
Group:
other: E000044146 challenge control
Dose level:
1:4 v/v dilution
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: E000044146 challenge control. Dose level: 1:4 v/v dilution. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no response.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: E000044146 challenge control
Dose level:
1:4 v/v dilution
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: E000044146 challenge control. Dose level: 1:4 v/v dilution. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no response.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.2% DNCB in 80% ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
well-defined or moderate to severe response in all animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.2% DNCB in 80% ethanol . No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: well-defined or moderate to severe response in all animals .
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.2% DNCB in 80% ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
well-defined erythema in all animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.2% DNCB in 80% ethanol . No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: well-defined erythema in all animals.
Reading:
1st reading
Hours after challenge:
24
Group:
other: DNCB challenge control
Dose level:
0.2%
No. with + reactions:
2
Total no. in group:
4
Clinical observations:
very slight erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: DNCB challenge control. Dose level: 0.2%. No with. + reactions: 2.0. Total no. in groups: 4.0. Clinical observations: very slight erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: DNCB challenge control
Dose level:
0.2%
No. with + reactions:
2
Total no. in group:
4
Clinical observations:
very slight erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: DNCB challenge control. Dose level: 0.2%. No with. + reactions: 2.0. Total no. in groups: 4.0. Clinical observations: very slight erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
mineral oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: mineral oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
mineral oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: mineral oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.

One test animal died following the 3rdinduction. No visible lesions were seen when examined post mortem.

Response grades, severity and incidence following challenge with a 1:4 v/v dilution of E000144700 did not produce a higher response than that observed for the negative control group.

 

The vehicle control group animals were free of dermal lesions throughout the study period.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
E000144700 was not a delayed contact sensitiser.
Executive summary:

The sensitization potential of E00014470 (CAS 68516-20-1) was investigated in male guinea pigs dermally exposed to a 1:2 v/v dilution of 0.5 mL E000144700 in mineral oil for each of 3 induction phases. Following challenge with a 1:4 dilution response grades, severity and incidence were not greater than those at the control group site. The positive control, DNCB, produced significantly higher responses than in the control group which were free of dermal lesions throughout the study period.

It is concluded that E000144700 (CAS 68516-20-1) is not a skin sensitiser and no classification is warranted under GHS/CLP.

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

Non human data

CAS 68516-20-1 (E000144700) was not a sensitiser in albino guinea pigs dermally exposed to a 1:2 dilution of E000144700 at a volume of 0.5 mL for 3 induction phases and to a 1:4 v/v dilution (in mineral oil) for the challenge (UBTL, 1990e). The data available on marker constituents: benzene, toluene, cyclohexane, and xylene indicate that they are not skin sensitisers.

Human data

Human data identified was for benzene and xylene (Kligman, 1966). The details of the study are not further discussed in the dossier due to ethical reasons.

References

Kligman AM (1966). The identification of contact allergens by human assay. III The maximization test: a procedure for screening and rating contact sensitizers. J Int Dermatol, 47 (5), 393-409.

Migrated from Short description of key information:

High Benzene Naphtha streams are considered not to be skin or respiratory sensitisers. The marker constituents: benzene, toluene, cyclohexane, and xylene are considered not to be skin sensitisers.

Justification for selection of skin sensitisation endpoint:

Information available for representative streams and the marker constituents present indicate no potential to induce or elicit skin sensitisation.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No specific animal or human data have been found with regard to respiratory sensitisation for any components within this stream.

Migrated from Short description of key information:

No data have been found concerning respiratory sensitisation and there are no indications that components within this stream are respiratory allergens.

Justification for classification or non-classification

There are sufficient data on CAS 68516-20-1 and on marker constituents to indicate that High Benzene Naphtha streams are not skin or respiratory sensitisers and no classification is warranted for these endpoints under Reg (EC) 1272/2008.