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Diss Factsheets

Administrative data

Description of key information

Buehler test: not sensitising

RA from CAS 4259-15-8

Guinea pig maximisation test: not sensitising

RA from CAS 4259-15-8

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:
28 Dec 1981 - 14 Jan 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study. Restriction due to missing details in study report. Missing details did not affect ability to evaluate effect of test substance on skin sensitisation.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: between 300 and 400 g
- Housing: the animals were housed and maintained in compliance with the Animal Welfare Act 9 CFR part 3. Five guinea pigs per cage were housed in stainless steel cages with elevated wire mesh flooring.
- Diet: Charles River Guinea Pig Formula was provided ad libitum.
- Water: tap water was provided ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 70 ± 2 °F
- Humidity (%): 45 ± 5
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28 December 1981 To: 14 January 1982
Route:
intradermal and epicutaneous
Vehicle:
other: white mineral oil
Concentration / amount:
5.0 % w/v
Route:
epicutaneous, occlusive
Vehicle:
other: white mineral oil
Concentration / amount:
5.0 % w/v
No. of animals per dose:
20 animals / dose
Details on study design:
RANGE FINDING TESTS: Unknown

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1 week following intradermal injection and 2 days (48 h) after dermal application.
- Test groups: 1 group of 20 male animals.
- Control group: Not included.
- Site: skin over the shoulders.
- Frequency of applications: For induction stage: intradermal injections were made once at 3 pairs of sites simultaneously, 7 days later followed by dermal application of test material. Then the animals were allowed to rest for 2 weeks.
- Duration: total of 3 week time period.

- Concentrations: 5% w/v

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 21 h
- Test groups: 1 group of 20 male animals.
- Control group: Not included.
- Site: skin over the shoulders.
- Concentrations: 5% w/v
- Evaluation (hr after challenge): 24 h and 48 h
Challenge controls:
Not included
Positive control substance(s):
not required
Positive control results:
n/a
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5% w/v
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% w/v
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
Conclusions:
CLP: not classified
Executive summary:

In a Magnusson-Kligman Guinea Pig maximization test, 20 Dunkin-Hartley strain albino Guinea Pigs were treated with 5.0% w/v test substance, Scores of zero in all test animals were obtained at all time points examined. The test material does not appear to be a sensitizer in the albino guinea pig.

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: Background irritation present
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:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc
- Weight at study initiation: 332-489 grams
- Housing: Housed individually in wire mesh suspension cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8-26.1
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction: 5% w/v
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Challenge: 1% w/v
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
Primary Irritation after 6 hour patch aplication of test material in mineral oil at following concentrations:

Undiluted, 50, 25, 10, 5, 2.5, 1, 0.5 % w/v

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Site: Left shoulder
- Frequency of applications: 6 to 7 days

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1 and 2 days (24 and 48 hours)
- Exposure period: 6 hours
- Control group: 10 naive not previously exposed to test material
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
10 naive not previously exposed to test material
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4,-Dinitrobenzene
Positive control results:
Positive for skin sensitization
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1%
No. with + reactions:
3
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1%
No. with + reactions:
1
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1%
No. with + reactions:
0
Total no. in group:
10

The irritation in 3/20 animals in the challenge phase scored after 24 hours did not persist to 48 hours, indicating an irritation response rather than a skin sensitization response.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for read-across

There are no reliable data available on skin sensitisation toxicitywith Phosphorodithioic acid, O,O-di-dodecyl-esters, zinc salts, neutral and basic (CAS 4563-56-8). Read-across from an appropriate substance Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS4259-15-8) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.3. Common functional groups, structural similarities and comparable toxicological properties of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

GPMT

A Guinea pig maximisation test was performed with Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) similar to the OECD Guideline 406 and under GLP conditions (Key, 1982). In the main study, 20 male Dunkin-Hartley guinea pigs were treated with the test substance at 5% (w/v) for intra- and epidermal induction on days 1 and 7, respectively. The dressing for epidermal induction was kept in place for 48 h. 14 days after the epidermal induction, epidermal challenge was performed with the test material at 5% (w/v). Positive control and negative controls were not included in the conducted study. 24 and 48 h after the challenge treatment skin examination revealed no skin reactions in the test groups. Under the conditions of the conducted study, the test substance was considered to be not skin sensitising.

Buehler test

A Buehler test was performed with Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) similar to the OECD Guideline 406 and under GLP conditions (Key, 1997). A range-finding study was conducted. In the main study, 20 male and female Hartley guinea pigs were treated three times with the test substance at 5% (w/v) for 6 h for epidermal induction. Thereafter, epidermal challenge was performed with the test material at 1% (w/v) after 24 and 48 h, respectively. 1-Chloro-2,4,-Dinitrobenzene was used as positive control and 10 naive guinea pigs which were not previously exposed to the test material was used as challenge control. In the treatment group 3/20 animals showed a positive result, which did not persist to 48 h, indicating an irritation response rather than a skin sensitising response. In the control group 1/10 animals showed a positive response after 24 h, which did not persist to 48 h. Positive control showed a positive result (not further specified). Under the conditions of the conducted study, the test substance was considered to be not skin sensitising.

A second Buehler test with the source substance Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) was available. In this study, there was a high level of background irritation present throughout the study (Supporting, 1986). Therefore the study was considered to be not reliable.

In conclusion, based on the results with the source substance, the target substance is not considered to exhibit a skin sensitising potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Applying the RA-approach, the available data on skin sensitisation do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.