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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with NTP guidelines, predates GLP, minor restrictions in design and reporting, but otherwise adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979

Materials and methods

Principles of method if other than guideline:
Subchronic feeding study was conducted to estimate the maximum tolerated dose (MTD) of sodium diethyldithiocarbamate. Groups of five rats of each sex were fed diets containing sodium diethyldithiocarbamate trihydrate at doses 1250, 2500, 5000, 10000, 20000 and 40000 ppm. The period of administration of the test chemical was 7 weeks, followed by 1 week of additional observation. At the end of the study, all animals were killed and necropsy and histopathological examinations were performed.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium diethyldithiocarbamate
EC Number:
205-710-6
EC Name:
Sodium diethyldithiocarbamate
Cas Number:
148-18-5
Molecular formula:
C5H11NS2.Na
IUPAC Name:
sodium (diethylcarbamothioyl)sulfanide

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: NCI Frederick Cancer Research Center animal farm (Frederick, Md.).
- Age at study initiation: 6 weeks
- Weight at study initiation: males 90 to 105 g, averating at least 100 g; females 80 to 95 g, averaging at least 90 g
- Housing: polycarbonate cages (Lab Products Inc., Gar field, N.J.), 19 x 10-1/2 x 8 inches
- Diet (e.g. ad libitum): presterilized Wayne Sterilizable Lab Meal, provided ad libitum in suspended stainless steel hoppers and replenished at least three times per week
- Water: acidified to pH 2.5, supplied a£ libitum from glass bottles
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 24 C
- Humidity (%): 45 to 55%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): every 1 to 1-1/2 weeks in 6- to 12-kg batches
- Mixing appropriate amounts with (Type of food): known weight of the chemical was first mixed with an equal weight of autoclaved Wayne Sterilizable Lab Meal with 4% fat (Allied Mills, Inc., Chicago, 111.), using a mortar and pestle. The mixing was continued with second and third additions of feed, and final mixing was performed with the remaining quantity of feed for a minimum of 15 minutes in a Patterson-Kelly twin-shell blender•
- Storage temperature of food: 5 C
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
7 weeks, followed by 1 week post-treatment observation
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
1250, 2500, 5000, 10000, 20000 and 40000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: twice a week


Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
Ten percent depression in body weight was the major criterion for estimation of MTD's. The doses required to produce this response were determined by the following procedure: first, least squares regressions of mean body weights versus days on study were used to estimate mean body weights of each of the dosed groups at day 49. Next, probits of the percent weights of dosed groups at day 49 relative to weights of corresponding control groups were plotted against the logarithms of the doses, and least squares regressions fitted to the data were used to estimate the doses required to induce 10% depression in weight.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
425 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Dose descriptor:
NOAEL
Effect level:
332 mg/kg bw/day (actual dose received)
Based on:
other: anhydrous substance
Sex:
male/female
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion