Orthosulfamuron

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 15 to August 8, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1981 and subsequent updating)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

(August 1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

n.a.

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

IR5878
ISO common name: Orthosulfamuron
Batch number: FCF/T/159-99 (ex 20274/71)
Purity: 93.72 ± 1.05 %

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

Test animals:
Species and Strain: Male Dunkin Hartley albino guinea pigs
Age: 6 weeks
Body weight: 375 ÷ 410 g
Housing: 2 or 3 animals/cage in air-conditioned room.
Feed: diet “8 GP 22” produced by Charles River Italia’s feed licensee Mucedola Srl, Settimo Milanese. The diet was supplemented by the Producer with vitamins and traces elements. The diet was available ad libitum to the animals. Water was distributed ad libitum to the animals.

Environmental conditions:
Temperature and humidity measured during the study were 22 ± 2°C and 55 ± 15%, respectively.
Light: artificial lighting with a 12-hour cycle (07:00 – 19:00).

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: vaseline oil

Concentration / amount:

0.1 mL/injection intradermally (concentration of 1%), 0.3 mL/patch (50% concentration) at booster (with sodium lauryl sulphate treatment on the previous day) and 0.2 mL/patch (50% concentration) at challenge (main test)

Day(s)/duration:

1

Adequacy of induction:

highest technically applicable concentration used

No. of animals per dose:

6

Details on study design:

IR5878 in vaseline oil was applied to Dunkin Hartley albino guinea pigs at 0.1 mL/injection intradermally (concentration of 1%), 0.3 mL/patch (50% concentration) at booster (with sodium lauryl sulphate treatment on the previous day) and 0.2 mL/patch (50% concentration) at challenge (main test).
In a preliminary test aliquots of 0.1 mL of 0.5 and 1% IR5878 in vaseline oil were injected intradermally to 2 guinea pigs (the 5% concentration was not injected because of the too high density) on two different areas of the shoulder region. Three occlusive patches containing 0.2 mL of 10, 25 and 50% of IR5878 in vaseline oil were applied for 24 hours on three different areas of the dorsal region of the same two animals treated intradermally. The patches were removed after 24 hours and the animals were observed for up to 48 hours for local reactions. 1% IR5878 in vaseline oil for intradermal injection and 50% IR5878 in vaseline oil were the two highest concentrations technically administrable, according to solubility data of the test substance. None of the concentrations assayed either by intradermal route or by patch application were irritant. Therefore in the main study the test article was used at concentration of 1% in vaseline oil (induction phase), at 50% in vaseline oil (booster; pre-treatment with sodium lauryl sulfate) and again at 50% in vaseline oil (challenge).

Study design: in vivo (LLNA)

Concentration:

1% for the intradermal injection
50% for the booster exposure
50% for the challenge applicaiton

No. of animals per dose:

group 1 treated animals number 1-20
group 2 control animals number 21-40

Results and discussion

In vivo (non-LLNA)

Results

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

6

Clinical observations:

24h after injections a moderate swollen reddish area was seen for FCA, FCA/vehicle and FCA/test article. Injection of the test article at 1% in the vehicle did not induce local changes, and no reaction was observed after injection of vehicle alone.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results and under the experimental conditions applied, IR5878 did not possess any sensitising potential to guinea pig skin.

Contact sensitivity is a T-lymphocyte mediated delayed hypersensitivity reaction. The immunological events in skin sensitization can be separated into two main phases:development of sensitization and elicitation of lcinical effects (eg erythema and edema) following subsequent exposure to the same compound.

The sensitizing potential of the test articla IR5878 was assessed in guinea pigs using the Magnusson test as described by Klecak (1), Magnusson B and Kligman A M.

No animals treated with the test article showed a positive reaction at the challenge. On the basis of this result under experimental conditions applied IR5878 dod not show sensitizing capacity.

Executive summary:

IR5878 in vaseline oil was applied to Dunkin Hartley albino guinea pigs at 0.1 mL/injection intradermally (concentration of 1%), 0.3 mL/patch (50% concentration) at booster (with sodium lauryl sulphate treatment on the previous day) and 0.2 mL/patch (50% concentration) at challenge (main test).

IR5878 did not possess any sensitising potential to guinea pig skin.