4-vinylpyridine

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo

Remarks:

Type of genotoxicity: other: assays results of mutational events

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Not an OECD Guideline study. 20-week tumorigenicty study performed by scientists at the American Health Foundation, under Grant # CA-29580 from the U.S. National Cancer Institute. This is a reputable research institute which was a long-time recipient of core center grants from the U.S. National Cancer Institute.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Female A/J mice 6-8 weeks old were housed in groups of 5 in polycarbonate cages with hardwood bedding, in rooms kept at 20 C on a 12-hour light/dark cycle, and fed NIH-07 meal and water ad lib. Each mouse, in a group of 25, was injected intraperitoneally 3 times weekly for 20 weeks with 2-vinylpyridine suspended in olive oil, for a total administration of 200 micromoles/mouse. Mice were euthanized and lung tumors were counted.

GLP compliance:

not specified

Type of assay:

other: lung tumor (adenoma, adenocarcinoma) induction

Test material

Test material information

Constituent 1

Reference substance name:

4-vinylpyridine

EC Number:

202-852-0

EC Name:

4-vinylpyridine

Cas Number:

100-43-6

Molecular formula:

C7H7N

IUPAC Name:

4-ethenylpyridine

Constituent 2

Reference substance name:

202-853-0

IUPAC Name:

202-853-0

Test material form:

other: liquid

Details on test material:

4-Vinylpyridine was obtained commercially and purified by acid precipation. Purity was 99%, verified by GC-FID on an Alltech Econocap Carbowax column. 4-vinylpyridine was suspended in olive oil and stability was assessed after 1, 2, and 3 weeks. After 3 weeks of storage, there was 94.8% recovery in the olive oil. Test solutions administered to mice were made fresh weekly.

Test animals

Species:

mouse

Strain:

other: A/J, from Jackson Laboratories, Bar Harbor, ME, USA

Sex:

female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Olive oil

Duration of treatment / exposure:

3 weeks (20 days)

Frequency of treatment:

3 injections weekly

Post exposure period:

20 weeks

No. of animals per sex per dose:

25

Control animals:

yes, concurrent vehicle

Positive control(s):

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Examinations

Tissues and cell types examined:

A complete autopsy of each mouse was performed. The following tissues were sliced and preserved in buffered formalin: head, lung, heart, liver, spleen, pancreas, kidneys and adrenals.

Details of tissue and slide preparation:

Tissues were preserved in formalin with buffer. Paraffin sections were prepared and stained with H&E, and examined histologically.

Evaluation criteria:

Incidence of tumors was compared between the mice dosed with test material and control mice receiving vehicle. Histological lesions were compared with those of the negative and positive controls (NNK and styrene).

Statistics:

Statistical significance was evaluated by the Student's t-test.

Results and discussion

Test results

Sex:

female

Genotoxicity:

negative

Remarks:

not tumorigenic

Toxicity:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

In vitro genotoxicity testing was performed on 4-vinylpyridine. This substance was non-mutagenic in a bacterial mutagenesis assay (Ames Assay) in Salmonella strains TA1535, TA 1537, TA 98 and TA 100 with and without exogenous activation by liver S9 fractions. 1-vinylpyridine was non-genotoxic in a primary hepatocyte/DNA repair assay (Williams Assay).

Any other information on results incl. tables

17 % of mice treated with 4VP developed lung tumors after 20 weeks of i.p. administration of a total dose of 200 micromoles, compared with 4% of control mice (increase was not statistically significant), and 100% of mice given 20 micromoles of NNK (positive control). The number of 4 -VP-dosed mice with lung adenomas was 4, compared with 1 in negative controls and 24 in the NNK group.

The number of 4-VP-dosed mice with lung adenocarcinomas was 0, compared with 0 in negative controls and 4 in the NNK group. The tumor burden per mouse in the 4-VP-dosed mice was 0.26 +/- 0.28, compared with 0.04 +/1 0.20 in negative controls and 24.0 +/- 7.0 in those receiving NNK. No other tumors were noted in the other tissues examined.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative non-carcinogenic
4-Vinylpyridine is non-tumorigenic in the lung after 20 weeks of exposure. If 4-vinylpyridine was mutagenic in vivo, there is a high probability that tumors would have developed as an effect of initiating genotoxic events. The absence of an increase in tumors in 4-VP-dosed animals over negative control values supports the proposal that 4-vinylpyridine is nonmutagenic in vivo.

Executive summary:

4-Vinylpyridine, 99% pure and stable in olive oil, was administered intraperitoneally to female A/J mice for a total dose of 200 micromoles. Mice were injected 3 times weekly for 20 weeks with 4-vinylpyridine suspended in olive oil.. Olive oil alone served as a negative control, and a known lung carcinogen, NNK, was given i.p. as a positive control. At the end of the 20 weeks, mice were euthanized and tissues were examined for tumors. There was no statistically significant difference in the number of mice with tumors, nor the number of tumors per mouse, between those receiving 4-vinylpyridine and the negative control group. In contrast, NNK significantly increased the number of mice with lung tumors, and also the number of tumors per animal which did have lung tumors, compared with negative controls. In conclusion, 4-vinylpyridine is not tumorigenic, and not mutagenic, in A/J mice when 200 micromoles is given over 20 weeks.