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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study, published in peer-reviewed literature, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Risk Assessments of Dithiocarbamate Accelerator Residues in Latex-based Medical Devices: Genotoxicity Considerations.
Author:
Tinkler J, Gott D and Bootman J
Year:
1998
Bibliographic source:
Food and Chemical Toxicology 36, 849-866

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
UKEMS Basic Mutagenicity Test Guidelines, 1990
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): zinc dibuthildithiocarbamate, ZDBC
- Physical state: fine white, aggregative powder
- Analytical purity: min. 98%
- Impurities (identity and concentrations): 28 ppm ZDMC, 17 pm ZDEC

Method

Species / strain
Species / strain / cell type:
other: TA 1535, TA 1537, TA1538, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S-9 homogenate from Aroclor 1254-induced adult male Sprague-Dawley rat livers
Test concentrations with justification for top dose:
25, 79, 250, 790 and 2500 µg/plate; in additional experiment with TA100 2.5-250 µg/plate.
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
Migrated to IUCLID6: 2 µg/plate, without S9
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
Migrated to IUCLID6: 5 µg/plate, with and without S9
Details on test system and experimental conditions:
The test design included a preliminary toxicity test and a mutation assay using the standard pour plate procedure, followed by an independent repeat experiment. An additional assay in TA 100 was performed at lower concentrations (2.5-250 µg/plate) in view of the toxicity seen in the first mutation experiment with this strain.

Results and discussion

Test results
Key result
Species / strain:
other: TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 2500 µg/plate; at TA100 also at 250 and 790 µg/plate
Additional information on results:
Inhibition growth was seen in all strains at the highest dose tested (also at 250 and 790 µg/plate in TA100). There was no increase in the number of revertants observed in any strain, in either presence or absence of S9-mix.

Any other information on results incl. tables

Mean numbers of revertants observed in Salmonella typhimurium TA 100 cultures following exposure to ZDBC at various concentrations.

 

 

 

Mean revertants (+/- SD)

Test substance

Concentration (µg/plate)

Activation system

Experiment 1

Experiment 2

ZDBC

2.5

-

NT

117 +/-5

7.9

-

NT

106 +/- 14

25

-

149 +/- 12

100 +/- 5

79

-

109 +/-7

97 +/- 8

250

-

140 +/- 4*

110 +/- 22*

790

-

90 +/- 57*

64 +/- 4

2500

-

21 +/- 22**

18 +/-3*

2.5

+

NT

95 +/- 8

7.9

+

NT

112 +/-6

25

+

147 +/-31

112 +/- 16

79

+

118 +/- 79

121 +/- 13

250

+

43 +/- 40*

94 +/- 11*

790

+

32 +/- 9*

49 +/- 28*

2500

+

30 +/- 8*

16 +_/- 6*

DMSO

 

-

135 +/- 9

127 +/- 7

DMSO

 

+

120 +/-6

127 +/- 8

Sodium azide

2

-

683 +/-95

963 +/- 74

Benzo[α]pyrene

5

-

132 +/- 25

115 +/-10

Benzo[α]pyrene

5

+

606 +/- 109

766 +/- 60

NT = not tested; *= toxic effect on tester strain was evident.

Applicant's summary and conclusion