4-vinylpyridine

Endpoint summary

Description of key information

Several repeated dose oral toxicity studies in rats on a 4VP analogue, 2VP,  are available which suggest a systemic NOAEL between 20 and 50 mg/kg bw/d.  There is no evidence of specific target organ toxicity; only signs of minor  toxicity such as changes in food consumption, altered body weight gain, and changes in relative organ weights.  Concerning local effects, 2VP displayed corrosive effects at the portal of entry, the nonglandular stomach.  The LOAEL for this effect was 20 mg/kg bw/d in the 90-day study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

20 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Adequate

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A close structural analogue of 4 -vinylpyridine, 2 -vinylpyridine, was studied in a 90-day repeated dose oral toxicity study in CD rats (Vlaovic, 1994). Read-across from the structural analogue is valid based on common functional groups and similar properties in physical and biological systems. This is especially the case concerning parameters which affect bioavailability, such as molecular size, water solubility, and octanol-water partition coefficient. 4VP is corrosive, and Regulation EC No. 1907/2006 discourages the testing of corrosive substances in vivo (Introduction to Annex IX, Standard Information Requirements). Doses (20, 60 and 180 mg/kg bw/d) were administered five days per week for 92 days. The high dose was considered toxic, with the major finding being reduced feed consumption in males and reduced body weight gain in males. Minor effects included slight changes in hematology and clinical chemistry values, and selected absolute and relative organs weight changes, not all of which were dose-related. The high dose (180 mg/kg/day) was clearly irritating to the non-glandular stomach epithelium of both sexes and microscopically was characterized by degeneration, hyperkeratosis and acanthosis resulting in a thickening of the non-glandular epithelium. The mid dose(60 mg/kg/day) produced a slight but statistically significant increase in liver weight relative to body weight (males) and relative to brain weight in female rats, which showed a dose relationship. Levels of Aspartate aminotransferase enzyme in the blood were also elevated. No histopathology in the liver (or any other organ other than stomach) was noted. Gross and histopathological changes in the stomach, seen in all repeat dose studies, are ascribed to local irritation of the test material.  The authors of the 90-day study identified the LOAEL for systemic effects to be 60 mg/kg bw/d, and the NOAEL to be 20 mg/kg bw/d. The LOAEL for local effects in the stomach was 20 mg/kg bw/d.

These conclusions are generally consistent with the findings in a 28-day study by Oba, et.al, 1997, where 2VP was administered by gavage to CD rats at doses of 12.5, 50 and 200 mg/kg bw/d. Decreased body weight gain and organ weight changes occurred in the high dose group, along with histopathologically-confirmed irritation effects in the forestomach (consistent with local corrosive effects). In the mid dose group of 50 mg/kg bw/d, there were no significant findings other than irritation effects in the stomach. The low dose group of 12.5 mg/kg bw/d did not show gastrointestinal irritation effects.

The systemic NOAEL is 20 mg/kg bw/day from the 90-day study of Vlaovic (1984), based on the absence of substance-related effects other than non-glandular stomach effects. The local LOAEL is 20 mg/kg bw/day, as there were minimal irritation effects in the stomach from repeated oral administration of a corrosive substance. In the 28-day study (Oba, et.al, 1997), the local NOAEL is 12.5 mg/kg bw/day, consistent with a local NOAEL of less than 20 mg/kg bw/day from the Vlaovic study.

From an exposure-based perspective, this substance is not one which will be available for oral consumption as food or in food contact materials. It is a reactive monomer for polymer formation and is bound in a polymer matrix after synthetic reactions take place. Hence, the likelihood that either workers or the general public would be orally exposed to the substance is negligible.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
A 90-day repeated-dose toxicity study on a close structural analogue, 2VP, is available and is valid with restrictions.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach

Justification for classification or non-classification

The classification is based on "read-across" from 2 -vinylpyridine, which is a close structural analogue of 4 -vinylpyridine. Repeated dose studies reported for 2 -vinylpyridine indicate that there is no evidence of systemic toxic effects to specific organs after repeated dose exposure in rats. There is no indication for a classification of Specific Target Organ Toxicity. Minor toxicity effects (decreased weight gain, liver weight/function changes) are observed at concentrations of 60 mg/kg bw/day or higher for 90 days. Local irritation effects in the stomach are not specific to any particular organ, but rather are nonspecific corrosive effects associated with site of contact (portal of entry). 4-Vinylpyridine is classified as corrosive to skin, eye and to the respiratory tract, which will insure that workers are advised to wear protective clothing and minimize breathing of the substance. The substance is not expected to be ingested.