Pyridine

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

other: secondary source

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Literature review by a reputable authoritative body (USA)

Data source

Reference

Reference Type:

secondary source

Title:

Pyridine, CAS 110-86-1

Author:

Anonymous

Year:

1992

Bibliographic source:

Agency for Toxic Substances and Disease Registry (ATSDR), http://www.atsdr.cdc.gov/tfacts52.pdf

Materials and methods

Study type:

other: literature review

Endpoint addressed:

other: health effects

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

literature review

Test material

Test material information

Constituent 1

Reference substance name:

Pyridine

EC Number:

203-809-9

EC Name:

Pyridine

Cas Number:

110-86-1

Molecular formula:

C5H5N

IUPAC Name:

pyridine

Results and discussion

Results:

The health effects resulting from exposure to pyridine have not been well studied. Other than LC50 data, there are no quantitative studies in humans or animals on the effects from inhalation exposure to pyridine, so no inhalation minimum risk level (MRLs) can be derived. By the oral route, there is limited evidence from older (1943) case studies in humans that the liver is a target tissue for pyridine, and this is supported by a recent study in rats (Anderson 1987). However, it is not certain that hepatotoxicity is the most sensitive end point, since pyridine may cause neurobehavioral effects at lower exposure levels (Anderson 1987). Because of the lack of confidence in the most sensitive end point and the sparsity of quantitative data on the NOAEL for hepatotoxic and neurotoxic effects, no oral MRLs can be derived at present. Similarly, no dermal MRLs can be calculated, due both to a lack of quantitative dermal dose-response data, and the lack of an appropriate methodology for development of dermal MRLs.

No deaths that are clearly attributable to pyridine have been reported in humans. The levels of pyridine necessary to cause death in animals are very high. Reported l-hour validation LC50 values for rats were approximately 9,000 ppm (Vernot et al. 1977), and the acute oral LD50 value in rats was 1,580 mg/kg (Smyth et al. 1951). No compound-related deaths were reported in rats that received pyridine by gavage for 90 days at levels up to 50 mg/kg/day (Anderson 1987). Therefore, it appears to be unlikely that inhalation or ingestion of the low levels of pyridine that may be present in air, water, or food would present a concern for lethality in humans. A possible exception may be laboratory or industrial settings where accidental exposure to high levels of pyridine can occur.

Hepatic Effects. Hepatic effects are the major potential health concern associated with exposure to pyridine. There is no clear evidence of hepatic effects associated with human exposure to pyridine. In a go-day gavage study in Sprague-Dawley rats, however, increased liver weight and inflammatory hepatic lesions were found (Anderson 1987). These observations suggest that human exposure to pyridine via the oral route may pose a concern for adverse liver effects. It is important to note that this concern is based on the results of a single study.

Renal Effects. There is no information on renal effects associated with human exposure to pyridine. Observations of degeneration of the renal tubular epithelium were reported in studies in which pyridine citrate was administered to male rats for up to 4 months (Baxter 1948). The currently available data suggest that exposure to pyridine may be associated with potential renal effects in humans.

Other Systemic Effects. There is no clear evidence of other systemic effects in association with human exposure to pyridine. However, decreased weight gain in developing rats during a go-day gavage study (Anderson 1987) suggests that this may be an area of concern associated with exposure to pyridine.

Immunological Effects. There are no studies of immunological effects in humans or animals exposed to pyridine via any route of exposure.

Neurological Effects. There are few studies of neurological effects in humans exposed to pyridine via any route of exposure. Pyridine is a central nervous system depressant. Neurological effects in man (nonpatients) have been noted by Pollock et al. (1943) and Neff (1886). Slow and slurred speech, slow reflexes, and a stuporous condition were reported to occur in an epilepsy patient who had been receiving other drugs in addition to pyridine (Pollock et al. 1943). Because of the existing disease state and the co-administration of other drugs, this information can only be viewed as suggestive evidence that exposure to pyridine can result in neurological effects in humans. Healthy adults, exposed to undetermined amounts of pyridine vapors, developed symptomatology which included some neurological effects. Included were slight temporal headaches, sensations approaching giddiness, a desire to sleep, and quickening of pulse and respiration (Neff 1886).

Developmental Effects. There are no studies of developmental effects in humans or animals exposed to pyridine via the inhalation, oral, or dermal routes. Because of the test system and extremely high doses of pyridine used, the relevance of these findings to the potential effects of pyridine on human development is not clear. However, this study constitutes the only investigation of the effects of pyridine on prenatal development; therefore, these findings warrant some consideration.

Reproductive Effects. No studies were located on reproductive effects of pyridine in humans or animals after any route of exposure.

Genotoxic Effects. No studies were located concerning genotoxic effects of pyridine in humans after any route of exposure. The only available in vivo study in animals provides no evidence that exposure to pyridine is potentially genotoxic. Negative results were reported in a micronucleus test in which single doses of pyridine were administered to mice by gavage at levels up to 1,000 mg/kg (Harper et al. 1984).

In vitro genotoxicity data for pyridine also indicate that pyridine does not show genotoxic potential. The results of tests for chromosomal aberrations using Chinese hamster ovary cells were negative (Ishidate and Odashima 1977) and sister chromatid exchange assays were weakly positive (Abe and Sasaki 1977). Results of assays using several strains of Salmonella tvphimurium have all been negative (Aeschbacher et al. 1989; Commoner 1976; Riebe et al. 2982; Seixas et al. 1982), as well as the pol A+/pol A- assay in Escherichia coli (Riebe et al. 1982).

Cancer. No studies were located of carcinogenic effects of pyridine exposure in humans or animals by any route of exposure.

Applicant's summary and conclusion

Conclusions:

The health effects of exposure to pyridine have not been well studied. No minimum risk levels (MRLs) are developed for pyridine.