Bis[bis(3,5,5-trimethylhexyl)dithiocarbamate-S,S']zinc

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Three invitro studies are reviewed.

No mutations were observed in bacterial strains, no cytogenicity was observed in human lymphocytes with respect to sister chromosome abberrations, and finally no cytotoxicty was observed in human lung fibroblasts

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 1- June 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Ames test 5 Salmonella strains and triplicate plates

Version / remarks:

oecd short term tox group - no Ecoli strain

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Purity 98%
BN 2152
stored at room temperature

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

with S-9 mix ( 2 aminoanthracene for strains TA1535, TA1537, TA1538, TA98 and TA100

Test concentrations with justification for top dose:

On each bacterial strain, four concentrations of test substance was assessed. he highest concentration will usually be 0.05g of test substnce dissolved in 1.0ml of solvent. Three 10 fld serial dilutions of the top concentrations will also be tested.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

other: 2 aminoanthracene

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Zinc Diisononyldithiocarbamate was non toxic towards the tester strains. Therefore the 5000 microgramme/plate was chosen as the top dose level in mutation tests.
The mean number of revertant colonies, together with the individual plate counts for Zinc Diisononyldithiocarbamate obtained in the first mutation test with tester strains TA 1535, TA1538, TA98 anmd TA100 are shown in tbale 2 and the sterility and positive controls in table 3.

No substantial increases int he revertant colony numbers of any of the five strains were observed following treatment with Zinc Diisononyldithiocarbamate at any dose level, either in presence or absence of liver microsomal fraction (S9 mix)

Conclusions:

No evidence of mutagneic potential of test item was obtained in this bacterial test system.

Reference 2

Endpoint:

in vitro cytogenicity / micronucleus study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

evaluated sister chromatid exchange, chromosome aberrations, micro nulcie, mitotic index and cell cycle distribution. The functionality of the tests was ensured by suitable positive controls.

Principles of method if other than guideline:

- Principle of test:
- Short description of test conditions: Zinc diisononyldithiocarbamates at three concentrations was investigated cytogenetically on lymph cell cultures from various probands. The incubation period, with external activation was 21h. In the presence of an external metabolic activating system ( acroclor - induced rat liver microsomes) the peroid of incubation was 1h and 2h
- Parameters analysed / observed:evaluated sister chromatid exchange, chromosome aberrations, micro nulcie, mitotic index and cell cycle distribution. The functionality of the tests was ensured by suitable positive controls.

GLP compliance:

no

Type of assay:

other: in vitro cytogenic mutagenicity study in human blood lymphocytes to detect chromosome aberration, sister chromatid exchanges, miconulcei, mitosis index and cell cycle distribution

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

mitomycin C

Statistics:

t test used

Key result

Species / strain:

lymphocytes:

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not valid

Positive controls validity:

valid

Remarks on result:

not measured/tested

SCE analysis: 50 metaphases of secnd cell cycle were assessed & SCE number determined

CA rates: 50 metaphases assessed.

Miconuclei rates: depending upon the scatter of values, 3 - 4 counts each of 1000 cells

Mitosis index, depending upon the scatter of values, 3 - 4 counts each of 1000 cells

Cell cycle distribution

Conclusions:

Under all test conditions the results give no indication of a cytogenetically detectable mutagenic effect due to test item

Reference 3

Endpoint:

genetic toxicity in vitro, other

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

aug 1994

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other: BS 5736 Part 10 (1988)

Version / remarks:

evaluation of medical devices for biological hazards

Deviations:

not specified

GLP compliance:

not specified

Type of assay:

other: Cytoxicity to Embryonic human lung fibroblasts

Specific details on test material used for the study:

BN 93102
date tested 31 aug 1994

Species / strain / cell type:

mammalian cell line, other: lung fibroblasts

Details on mammalian cell type (if applicable):

MRC 5 embryonic human lung cells

Test concentrations with justification for top dose:

test sample was prepared as 10mg/ml suspension which was double diluted with vigorous mixing down to 1/16th prior to incubation in culture media for 24 hours
top dose was 1% w/v concentratin

Rationale for test conditions:

Positive control discs - containing 0.57% dibutyl tin dimaleate
negative control - silicone rubber

Evaluation criteria:

by microscopic examination of fixed and stained cultures.
Criteria
0 - no cells showing damage
1 - up to 25% of cells showing damage
2- 25-50% of cells showing damage
3. 50-75% of cells showing damage
4. > 75% of celss showing damage

Conclusions:

No cytotoxic effects were observed in all dilutions including neat test item ( 1%w/v)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)