Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
deviation: for technical reasons, the stability in solvent could not be analyzed over the entire range of the formulations used in this study; however, this deviation did not limit the assessment of the results.
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
(2,4,6-trioxotriazine-1,3,5(2H,4H,6H)-triyl)tris(methyl-m-phenylene) isocyanate
EC Number:
247-840-6
EC Name:
(2,4,6-trioxotriazine-1,3,5(2H,4H,6H)-triyl)tris(methyl-m-phenylene) isocyanate
Cas Number:
26603-40-7
Molecular formula:
C27H18N6O6
IUPAC Name:
1,3,5-tris(3-isocyanato-4-methylphenyl)-1,3,5-triazinane-2,4,6-trione
Constituent 2
Reference substance name:
TDI Trimer
IUPAC Name:
TDI Trimer

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced male rat liver S9 mix
Test concentrations with justification for top dose:
0, 100, 250, 500, 1000, 2500, 5000 µg/plate (without and with S9 mix)
Vehicle / solvent:
Solvents used: ethylene glycol dimethylether (EGDE) dried with a molecular sieve 0.3nm (test substance), phosphate buffer (sodium azide, mitomycin C, cumene hydroperoxide ), DMSO (nitrofurantoin, 4-nitro-1,2-phenylene diamine, 2-aminoanthracene)
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: sodium azide (TA 100, TA 1535), 2-nitro-9H-fluorene (TA 98), 4-nitro-o-phenylenediamine (TA 1537), mitomycin C (TA 102, plate incorp.), cumene hyd (TA 102, preincub. trials), 2-aminoanthracene (all strains)
Remarks:
The positive controls sodium azide, 2-nitro-9H-fluorene, 4-nitro-o-phenylenediamine, mitomycin C and cumene hydroperoxide were only used without S9 mix; the positive control 2-aminoanthracene was only used with S9 mix.
Evaluation criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, TA 1537, TA 100 and TA 98 this increase should be about twice that of negative controls. For TA 102 an increase of less than 2-fold is already considered as mutagenic effect due to the relatively high spontaneous revertant frequency of this strain. Otherwise, the result is evaluated as negative. However, these guidelines may be overruled by good scientific judgment. In case of questionable results, investigations should continue, possibly with modifications, until a final evaluation is possible.
Statistics:
Not specified.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: strain-specific bacteriotoxic effect at 2500 µg/plate and above
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Summary of results from the Salmonella mutagenicity assay (plate incorporation test) with Desmodur RC/100 (mean values of revertants per plate)

Dose (µg per plate)

Without metabolic activation

 

 TA 1535

 TA 100

 TA 1537

 TA 98

 TA 102

 Vehicle control (EGDE)

16

104

8

14

165

100

15

104

9

13

161

250

15

105

8

13

164

500

15

112

8

10

186

1000

14

100

8

10

160

2500

14

109

5

 7

164

5000

12

97 

 5

134 

 Positive control

612

654

79

667

519 

 Dose ( µg per plate )

With metabolic activation (liver S9 mix)

 

 TA 1535

 TA 100

 TA 1537

 TA 98

TA 102

 Vehicle control (EGDE)

14

109

12

34

233

100

15

118

11

29

206

250

16

91

13

29

222

500

13

126

13

21

197

1000

13

98

13

29

180

2500

12

101

9

28

206

5000

13 

84

25 

209 

 Positive control

130

882

88

364

499

Table 2: Summary of results from the Salmonella mutagenicity assay (independent preincubation test) with Desmodur RC/100 (mean values of revertants per plate)

 

Dose (µg per plate)

Without metabolic activation

 

 TA 1535

 TA 100

 TA 1537

 TA 98

 TA 102

 Vehicle control (EGDE)

14

94

7

16

196

100

15

94

5

20

191

250

12 

112 

18

211 

500

15 

 95

16 

175 

1000

13

82

5

17

176

2500

13

109

5

18

171

5000

12

90

5

20

190

 Positive control

699

721

77

668

583 

 Dose ( µg per plate )

With metabolic activation (liver S9 mix)

 

 TA 1535

 TA 100

 TA 1537

 TA 98

TA 102

 Vehicle control (EGDE)

17

130

18

38

266

100

18

136

18

41

284

250

17

132

18 

42

293 

500

18

132 

17

35

268 

1000

16

127

17

32

262

2500

18

125

14

40

269

5000

16

108

17

42

227

 Positive control

93

532

54

308

573

  

At 1000 µg per plate, the substance started to precipitate.

In the plate incorporation test doses of up to and including 1 000 mg per plate did not cause any bacteriotoxic effects. At higher doses, the substance had a strain-specific bacteriotoxic effect. Due to this effect this range could only partly be used up to 5000 µg per plate for assessment purposes.

In the preincubation test doses of up to and including 1000 µg per plate did not cause any bacteriotoxic effects. At higher doses, the substance had a strain-specific bacteriotoxic effect. Nevertheless, the complete dose range of up to and including 5000 mg per plate could be used for assessment purposes.

Evidence of mutagenic activity of Desmodur RC/100 was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed up to assessable doses.

The positive controls sodium azide, 2-nitro-9H-fluorene, 4-nitro-o-phenylenediamine, mitomycin C, cumene hydroperoxide and 2-aminoanthracene had a marked mutagenie effect, as was seen by a biologically relevant increase in mutant colonies compared to the corresponding negative controls.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative
Executive summary:

The mutagenic potential of Desmodur RC/100 was evaluated in a Salmonella/microsome test with the S. typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 in the presence and absence of S9 mix according to OECD TG 471. Evidence of mutagenic activity was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed. Based on this test, the test substance was considered to be non-mutagenic without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.