1,5-naphthylene diisocyanate

Genetic toxicity: in vitro

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

- no strains with an AT base pair at the primary reversion site (E. coli WP2 strains or S. typhimurium TA 102) were used to detect cross-linking mutagens

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,5-naphthylene diisocyanate

EC Number:

221-641-4

EC Name:

1,5-naphthylene diisocyanate

Cas Number:

3173-72-6

Molecular formula:

C12H6N2O2

IUPAC Name:

1,5-diisocyanatonaphthalene

Details on test material:

- Name of test material (as cited in study report): Desmodur 15 (1,5-Naphthylene diisocyanate)
- Physical state: solid
- Purity: 99.6 %
- Lot/batch No.: 113, 118, 126
- Storage condition of test material: room temperature

Method

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9 mix from Aroclor 1254 induced rat livers

Test concentrations with justification for top dose:

8, 40, 200, 1000, 5000 µg/plate (first trial),
50, 100, 200, 400, 800 µg/plate (second trial)

Vehicle / solvent:

Solvents used: ethylene glycol dimethylether (test substance), DMSO (positive control)

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: sodium azide, nitrofurantoin and 4-nitro-1,2-phenylene diamine were only used without S9 mix and 2-aminoanthracene was only used with S9 mix

Details on test system and experimental conditions:

METHOD: Standard plate test and preincubation test

Evaluation criteria:

CRITERIA FOR EVALUATING RESULTS: A reproducible and dose-related increase in mutant counts (at least twice the amount of vehicle controls) of at least one strain of bacteria is considered to be a positive result

Statistics:

not specified

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: bacteriotoxic effects at 200 µg/plate and above

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

PRECIPITATION CONCENTRATION:
At 200 µg per plate, the substance started to precipitate.

CYTOTOXIC CONCENTRATION:
There was no indication of a bacteriotoxic effect at doses of up and including 100 µg per plate. The total bacteria counts consistently produced results comparable to the negative controls, or differed only insignificantly. Nor was any inhibition of growth noted. Higher doses had a strain-specific bacteriotoxic effect. Therefore they could only be used to a limited extent up to 1000 µg per plate.

GENOTOXIC EFFECTS:
None of the four strains concerned showed a dose-related and biologically relevant increase in mutant counts over those of the negative controls. This applied both to the tests with and without S9 mix and was confirmed by the results of the repeat tests. The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine and 2-aminoanthracene increased mutant counts to well over those of the vehicle controls, and thus demonstrated the system's sensitivity and the activity of the S9 mix.

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 (first trial) with 1,5-NDI (mean values of revertants per plate)

Dose (µg per plate)	Without metabolic activation
	TA 98	TA 100	TA 1535	TA 1537
Solvent EGDE	21	92	13	6
8	25	96	13	8
40	28	108	10	8
200	16	45	11	3
1000	---	---	---	---
5000	---	---	---	---
Positive control	163	489	1012	83
Dose ( µg per plate )	With metabolic activation (liver S9 mix)
	TA 98	TA 100	TA 1535	TA 1537
Solvent EGDE	41	142	15	12
8	42	146	16	14
40	45	163	13	15
200	39	220	15	16
1000	---	172	---	---
5000	---	---	---	---
Positive control	581	903	263	89

Table 2: Summary of results from the Salmonella mutagenicity assay (second trial) with 1,5-NDI (mean values of revertants per plate)

Dose (µg per plate)	Without metabolic activation
	TA 98	TA 100	TA 1535	TA 1537
Solvent EGDE	26	60	8	10
50	20	69	6	7
100	20	68	7	6
200	11	36	4	3
400	---	0	---	0
800	---	---	0	---
Positive control	87	320	679	60
Dose ( µg per plate )	With metabolic activation (liver S9 mix)
	TA 98	TA 100	TA 1535	TA 1537
Solvent EGDE	40	121	13	16
50	44	160	16	18
100	47	137	13	17
200	49	166	13	17
400	40	96	13	10
800	---	97	---	---
Positive control	660	936	297	88

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Executive summary:

In an Ames test with the S. typhimurium strains TA 98, TA 100, TA 1535, and TA 1537 1,5-naphthylene diisocyanate revealed no mutagenic activity in the absence and in the presence of a metabolic activation system (OECD TG 471).