Disulfiram

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

25.03.-13.08.1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP - Guideline study, tested with the source substance tetramethylthiuram disulfide (CAS No. 137-26-8). In accordance to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance. (For detailed information on the justification of read-across, please refer to the analogue justification document attached in IUCLID section 13).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)

Deviations:

no

GLP compliance:

yes

Limit test:

no

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:

tetramethylthiuram disulfide

Details on test material:

- Name of test material (as cited in study report): Thiram
- Physical state: cramy white powder
- Analytical purity: 99 %
- Purity test date: 20.02.1994
- Lot/batch No.: V614/0801 AC
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in non-continuous artificial light

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

6 h/d for 21 (males) or 22 (females) consecutive days

Frequency of treatment:

21 (males) or 22 (females) consecutive days

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 300, 1000 mg/kg and day
Basis:
nominal per unit body weight

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

1

Dose descriptor:

NOEL

Effect level:

300 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: systemic effects

2

Dose descriptor:

LOAEL

Effect level:

1 000 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: systemic effects

3

Dose descriptor:

NOEL

Effect level:

< 100 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: dermal irritation

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Clinical signs:No treatment-related changes were observed.

Mortality: No deaths.

Local dermal irritation: Control group: no dermal signs. All treatment groups: slight or well-defined erythema with or without slight or well-defined oedema, with well-defined responses noted with greater frequency in the mid- and high-dose group. Reactions were observed initially in isolated incidences on Day 7 but over the following two weeks developed in the great majority of rabbits. These reactions were frequently accompanied by residual (brown) staining from the test substance and/or desquamation of the stratum corneum.

Bodyweight gain: Reduced bodyweight gain was observed in females dosed at 1000 mg/kg bw/day.

Food consumption: Reduction in mean food consumption was measured for females dosed at 1000 mg/kg bw/day throughout the study. These changes were statistically significant (p 0.05) in week 1 and 2.

Blood analysis: Haematology: No treatment-related changes. Clinical chemistry: Liver enzymes GOT, GPT, and cholesterol levels were increased in females dosed at 1000 mg/kg bw/day. Alkaline phosphatase activity was increased at 1000 mg/kg bw/day in both sexes.

Sacrifice and pathology: Organ weights: No dose-related effects.

Gross and histopathology: Gross pathology: no treatment-related effect.

Histopathology: Minimal generalised/focal acanthosis of epidermis at the treated skin sites of all male and female rabbits were considered treatment-related.