Registration Dossier

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:
EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

open allclose all
Dose descriptor:
NOEL
Effect level:
300 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: systemic effects
Dose descriptor:
LOAEL
Effect level:
1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: systemic effects
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.

Applicant's summary and conclusion