Formaldehyde, oligomeric reaction products with aniline

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Lacks compliance with contemporary guidelines. However this study is considered to provide adequate data for assessment.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Principles of method if other than guideline:

Ames et al ., Mut . Res ., 31, 347-364, (1975)

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4,4’-methylenedianiline

IUPAC Name:

4,4’-methylenedianiline

Constituent 2

Reference substance name:

4,4'-methylenedianiline

EC Number:

202-974-4

EC Name:

4,4'-methylenedianiline

Cas Number:

101-77-9

Molecular formula:

C13H14N2

IUPAC Name:

4,4'-methylenedianiline

Details on test material:

MDA, no further data

Method

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA 1537, TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced liver S9 from male sprague dawley rats

Test concentrations with justification for top dose:

3.5-3000 µg/plate

Vehicle / solvent:

- Vehicle/solvent used: DMSO

Controls

Untreated negative controls:

yes

Remarks:

(sterility control)

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: - S9: N-methyl-N'-nitro-N-nitrosoguanidine and Benzo(a)pyrene 4,5-oxide; +S9: 3-methylcholanthrene, benzo(a)pyrene, 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation);
DURATION
- Exposure duration: 2-3 days

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium, other: TA 98, TA 100, TA 1537, TA 1538

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium, other: TA 100, TA 98, TA 1538

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

Negative in absence of S-9
Positive in presence of S-9 with TA 100, weakly positive with TA 98 and TA 1538 (dose dependent).
Negative inpresence of S-9 with TA 1537.
Positive with doses of 30 µg/plate, in a dose dependent manner.

Remarks on result:

other: other: S. typhimurium TA 98, TA 100, TA 1537, TA 1538

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: his+ revertants in presence of S-9 mix

Dose [µg/plate]	TA100 Exp.1	TA100 Exp.1	TA100 Exp.2	TA100 Exp.2	TA1537	TA1537	TA98	TA98	TA1538	TA1538
0	182	202	139	151	12	17	35	47	32	32
0	190	174	143	134	12	11	48	36	32	34
3.15	180	281	-	-	13	13	-	-	-	-
10	270	760	276	326	13	12	69	115	28	-
31.5	840	1060	530	674	13	12	112	105	33	35
100	1260	850	1130	1070	15	14	167	140	52	45
315	1170	1020	1240	1560	10	10	225	217	52	42
1000	2050	2410	-	-	16	17	-	-	-	-
3000	1260	1730	-	-	11	14	-	-	-	-
P1	1300	1390	1390	1280	210	184	800	850	242	280
P2	5800	5300	5600	5800	355	490	5700	4900	1960	2110
P3	5600	4600	2950	2820	118	108	1470	1510	87	64

P1 = 10 µg/plate Benzo(a)pyrene

P2 = 10 µg/plate 2-Aminoanthracene

P3 = 90 µg/plate3-Methylcholanthrene

 

- the mutagenic potential was relatively strong with TA 100. The mutagenicity (expressed as mutations per µg of test compound under optimal conditions) of phenylbase, an aromatic amine, was about 25 times weaker with TA 100 than that of the positive control 2-aminoanthracen. In TA 98 and TA 1538 the mutagenic potential was less pronounced than in TA 100.

Similar results from 3 to 333 µg/plate reported by Zieger et al 1988, using rat and hamster liver S-9.

Applicant's summary and conclusion

Conclusions:

Positive in the presence of a metabolic activation system.

NOTE FOR III: This is reported in the EU Risk assessment – original report not in Scientific Office. The SO has a translated document hand marked 77/207, which may be an unofficial translation of the report – this is not marked as to any ownership or test lab, but is signed and dated: Prof F Oesch, Mainz, 13 December 1977