Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, available as unpulished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): sodium dibutyldithiocarbamate (perkacit SDBC liq-w47%)
- Physical state: clear light yellow liquid
- Analytical purity: 46.20% (concentrated aqueous solution)
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10-11 weeks old
- Weight at study initiation: +/- 20% of the sex mean
- Fasting period before study: overnight
- Housing: group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7 – 21.5
- Humidity (%): 38 - 73
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- % coverage: 100
- Type of wrap if used: a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water for animals at 1000 mg/kg
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (1.887 mL/kg) bw and 1000 mg/kg (0.943 mL/kg) bw.
- Concentration (if solution):
- Constant concentration used: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): 1.887 mL/kg (2000 mg/kg) bw and 0.943 mL/kg (1000 mg/kg) bw.
Duration of exposure:
24 hours for 1000 mg/kg bw dose groups; animals at 2000 mg/kg were found dead or were killed in extremis between 2 and 4 hours after application.
Doses:
1000 and 2000 mg/kg bw
No. of animals per sex per dose:
For 2000 mg/kg bw: 5/sex/dose; for 1000 mg/kg bw: 3 females/dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: for 2000 mg/kg bw, one male and four females died between 2 and 4 hours after application of the test substance, and, subsequently, the remaining female and four males at 2000 mg/kg were killed in extremis. At 1000 mg/kg one female was found dead on Day 1 and the remaining two females at 1000 mg/kg were killed in extremis on Day 8.
- Frequency of observations and weighing: Days 1 (pre-administration) and 8.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The treated skin of the two animals at 1000 mg/kg that were killed in extremis showed severe effects such as necrosis and a wound and these animals were hypersensitive to touch of the treated skin. The data correspond to 46.2% solution of SDBC.
Mortality:
Between 2 and 4 hours after application of the test substance, one male and four females at 2000 mg/kg were found dead and, subsequently, the remaining female and four males at 2000 mg/kg were killed in extremis. One female at 1000 mg/kg was found dead on Day 1 and the remaining two females at 1000 mg/kg were killed in extremis on Day 8.
Clinical signs:
Individual animals at 2000 mg/kg showed general muscle twitching or lethargy at two hours post-treatment.
The animal at 1000 mg/kg that died on Day 1 showed lethargy, hunched posture, uncoordinated movements, shallow respiration, piloerection, chromodacryorrhoea (left eye) and ptosis prior to death. A combination of the following clinical signs were observed between Days 1 and 8 for the two animals at 1000 mg/kg that were killed in extremis on Day 8: lethargy, general tremor, flat or hunched posture, uncoordinated movements, shallow respiration, piloerection, watery discharge from the eyes, chromodacryorrhoea of the snout, hypersensitivity to touch of the treated skin and ptosis. In addition, these two animals showed focal erythema, necrosis, scabs, a wound and/or a thickened area in the treated skin-area between Days 2 and 8.
Body weight:
The two females at 1000 mg/kg that were killed in extremis on Day 8 showed changes in body weight gain over the first week post-treatment which were within the range expected for rats used in this type of study.
Gross pathology:
The two females at 1000 mg/kg that were killed in extremis on Day 8 showed isolated or several scab formations in the dorso-lumbar region of the skin at macroscopic post mortem examination. No abnormalities were found at macroscopic post mortem examination of the animals at 2000 mg/kg and 1000 mg/kg that were found dead or killed in extremis on Day 1.
Other findings:
The treated skin of the two animals at 1000 mg/kg that were killed in extremis showed severe effects such as necrosis and a wound and these animals were hypersensitive to touch of the treated skin. These signs suggest that treatment with the test substance caused marked pain and distress due to corrosive or irritating properties of the test substance. According to the test guidelines, further testing of the test substance need not be carried out based on these findings. A worst-case approach has been adopted by the study director for classification and labeling of the test substance for acute dermal toxicity.

A worst case Category 1 dermal toxicity classification as proposed by Notox for SDBC (fatal in contact with skin, category 1) seems to be inconsistent with the findings of the study and the results obtained for SDMC.

Based on the observations reported in the study report the systemic dermal LD50 is considered to be around 1.000 mg/kg. Therefore, an assumption that the LD50 for dermal exposure is in the range of 200-1000 mg/kg appears to be justified and in line with the precautionary principle. This leads to a classification Category 3 (toxic by the dermal route).

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Based on the observations reported in the study report the systemic dermal LD50 is considered to be around 1.000 mg/kg. Therefore, an assumption that the LD50 for dermal exposure is in the range of 200-1000 mg/kg appears to be justified and in line with the precautionary principle. This leads to a classification Category 3 (toxic by the dermal route).