Thiram

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 Apr - 2 May 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 2002

Deviations:

yes

Remarks:

individual body weight at study termination was not reported

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Version / remarks:

adopted 1984

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Thiram

EC Number:

205-286-2

EC Name:

Thiram

Cas Number:

137-26-8

Molecular formula:

C6H12N2S4

IUPAC Name:

thiram

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Broekman Instituut, Someren, The Netherlands
- Age at study initiation: ca. 18-19 weeks
- Weight at study initiation: not reported
- Housing: individually in "Lurane" plastic cages
- Diet: pelleted standard laboratory diet (Hope Farms, Woerden), 100 g per day and animal
- Water : tap water, ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -21
- Humidity (%): 45 - 60
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 Apr 1985 To: 2 May 1985

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

other: Untreated flanks were used as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g of test substance was moistened with 0.5 mL of distilled water immediately before dosing.


NEGATIVE CONTROL
- Amount(s) applied (volume or weight): the right flank was covered without test substance as a negative control.

POSITIVE CONTROL: No positive control substance was applied. No positive control data was provided.

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: Approximately 10 cm² of the central back of the animals was clipped one day before treatment. The test substance was evenly spread on a patch of 6 cm² and applied to the left flank of each animal.
- Type of wrap if used: metalline wound dressing, attached to tape (Micropore) and wrapped in flexible bandage (Coban).


REMOVAL OF TEST SUBSTANCE
- Washing: tissue moistened with tap water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
Exposed skin sites were examined for signs of erythema and oedema and the responses were scored at 30-60 minutes, and approximately 24, 48 and 72 hours after patch removal. For reference the control site on the contra lateral flank was used. Examination time points: 0.5-1, 24, 48, 72 h after removal of the test patch.

SCORING SYSTEM:
- Method of calculation: According to Draize scoring system

Erythema 0-4:
0: No erythema, 1: very slight erythema (barely perceptible), 2: well-defined erythema, 3 moderate to severe erythema, 4: severe erythema (beet redness) to slight eschar formation (injuries in depth)

Edema 0-4:
0: No oedema, 1: very slight oedema (barely perceptible), 2: well-defined oedema (edges of area well-defined by definite raising), 3: moderate to severe oedema (raised approximately 1mm), 4: severe oedema (raised more than 1 mm extending beyond the area of exposure)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: 1 h and 24 h after patch removal, erythema of grade 1 were observed which were fully reversible at the 48 h reading time point.

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal 2 - 6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Results 3

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

1/6 animals showed erythema (scored with grade 1) at the 1 h and 24 h observation time point. No skin reaction was seen in this animals thereafter or in any other animal for any time point.

Summarized results can be found in Attachment 1 in the attached background material.

Applicant's summary and conclusion

Interpretation of results:

other: According to the classification criteria of the CLP Regulation (EU) No. 1272/2008, no classification is required.

Conclusions:

The study is in accordance with EPA OPP 81-5 (Acute Dermal Irritation) and GLP.
Under the conditions chosen, a single semi-occlusive application of the test substance to intact rabbit skin for 4 h elicited no dermal irritation. Overall, except of very slight erythema (score 1) observed in one animal persistent for 24 hours, no signs of dermal irritation including erythema and oedema were noted in the other treated animals. No other adverse effects to the treatment have been noted. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item for skin irritation is required.