1.1.1. Nomenclature

• Chem. Abstr. Serv. Reg. No.: 110-86-1
• Deleted CAS Reg. Nos: 6999-00-4; 45410-39-7; 62301-32-0; 82005-06-9; 85404-19-9; 85404-20-2; 152758-95-7; 163392-20-9
• Chem. Abstr. Name: Pyridine
• IUPAC Systematic Name: Pyridine
• Synonyms: Azabenzene; azine

1.1.2. Structural and molecular formulae and relative molecular mass

1.1.3. Chemical and physical properties of the pure substance

(a)

Description: Colourless liquid with a disagreeable odour (Budavari, 1998)

(b)

Boiling-point: 115.2 °C (Lide & Milne, 1996)

(c)

Melting-point: –41.6 °C (Lide & Milne, 1996)

(d)

Density: 0.9819 g/cm³ at 20 °C (Lide & Milne, 1996)

(e)

Spectroscopy data: Infrared (prism [15]; grating [12]), ultraviolet [9], nuclear magnetic resonance (proton [10200, V96]; C-13 [1201]) and mass spectral data have been reported (Sadtler Research Laboratories, 1980; Lide & Milne, 1996)

(f)

Solubility: Miscible with water, acetone, benzene, chloroform, diethyl ether and ethanol (Lide & Milne, 1996)

(g)

Volatility: Vapour pressure, 2.76 kPa at 25 °C (Lide & Milne, 1996); relative vapour density (air = 1), 2.73 (Verschueren, 1996)

(h)

Stability: Highly flammable; flash point, 20 °C (closed cup) (Budavari, 1998); explosive limits, 12.4% (upper), 1.8% (lower) by volume in air (American Conference of Governmental Industrial Hygienists, 1999)

(i)

Octanol/water partition coefficient (P): log P, 0.60/0.65 (Hansch et al., 1995)

(j)

Conversion factor¹: mg/m³ = 3.24 × ppm

1.1.4. Technical products and impurities

Pyridine is commercially available in several grades for specific applications. Specifications vary according to country but are usually greater than 99.8% purity by gas chromatographic analysis (Scriven et al., 1996; Burdick & Jackson, 1997).

Trade names for pyridine include: CP 32.

1.1.5. Analysis

Selected methods for the analysis of pyridine in various matrices are given in Table 1.

Table 1

Selected methods for the analysis of pyridine.

1.4.1. Natural occurrence

Pyridine is found among the volatile components of black tea (Vitzthum et al., 1975) and in the leaves and roots of Atropa belladonna (Burdock, 1995).

1.4.2. Occupational exposure

According to the 1981–83 National Occupational Exposure Survey (NOES, 1999), as many as 43 000 workers in the United States were potentially exposed to pyridine. Occupational exposure may occur by inhalation and dermal contact during its production by synthesis or by treatment and distillation of crude coal-tar, during the processing of oil-shale and at coke-oven works. Exposure may also occur during its wide use as a chemical intermediate and/or solvent (Santodonato et al., 1985; Agency for Toxic Substances and Disease Registry, 1992). Laboratory use appears to account for a large number of workers potentially exposed (Santodonato et al., 1985; NOES, 1999).

Few data, especially recent data, are available on occupational exposure levels of pyridine. In 1978, the United States Pyridine Task Force of the Interagency Testing Committee reported that in United States workplaces where pyridine was manufactured or used as a chemical intermediate or as a solvent, workers were exposed to 8-h time-weighted average (TWA) pyridine concentrations ranging from 0.008 to 1.0 ppm [0.026 to 3.24 mg/m³]. Technicians working in quality control and research and development laboratories of one of the pyridine manufacturers were exposed to TWA concentrations (measured over 6-h periods) of no more than 0.09 ppm [0.29 mg/m³] (Santodonato et al., 1985).

A few studies have evaluated exposure levels in industries where pyridine originates from coal or coal-tar or where coal-tar products are processed or used. In a pyridine production shop of a coal-tar manufacture in the former USSR, pyridine levels were 7.5–10 mg/m³ and occasionally reached 20 mg/m³ (Izmerov, 1984). Mašek (1981) measured airborne concentrations in various industries in former Czechoslovakia. Values ranged from 0.005 to 2.98 mg/m³ [0.0015–0.92 ppm] in coking plants, from 0.005 to 0.135 mg/m³ [0.0015–0.042 ppm] in blast furnaces and steel works and from 0.010 to 0.630 mg/m³ [0.0031–0.195 ppm] in rolling mills and foundries. More recently, Bienik et al. (1993) reported personal exposure levels ranging from 0.002 to 0.7 mg/m³ [0.00062–0.22 ppm] (24 workers) in a Polish carbochemical plant. A study in a United States laboratory conducting research on coal conversion technology found no level of pyridine greater than 0.2 ppm [0.65 mg/m³] throughout the 1979–82 sampling period (Dreibelbis et al., 1982).

Air samples were collected in the moulding and pouring departments of a United States iron foundry using a phenolic urethane binder. The two-day average level of pyridine, emitted as a breakdown product of 4-phenylpropylpyridine used as a binder catalyst, was 5.9 ppm [19.1 mg/m³] in the moulding area (Apol, 1982). Pyridine as a possible pyrolysis product was not detected (< 0.1 ppm) [0.32 mg/m³] near a nylon injection-moulding operation of a United States electrical components production plant (Hartle & Erhenberg, 1985).

1.4.3. Environmental occurrence

The production of pyridine and its wide use as a solvent and as an intermediate in the synthesis of piperidine and a wide variety of drugs, insecticides and herbicides and chemicals used in rubber vulcanization may result in its release into the environment (Jori et al., 1983; Agency for Toxic Substances Disease Registry, 1992; Environmental Protection Agency, 1999). Pyridine occurs in the environment as a by-product of coal gasification (Stuermer et al., 1982).

Pyridine and its homologues are produced in coking procedures and present in the non-condensable gases. Pyridine is also present in coal-tar and as a component in creosote (Agency for Toxic Substances Disease Registry, 1992; Dutch Ministry of Social Affairs and Employment, 1993).

3.1.1. Mouse

Groups of 50 male and 50 female B6C3F₁ mice, seven weeks of age, were exposed to pyridine (purity, 99.8%) in the drinking-water at concentrations of 0, 250, 500 or 1000 mg/L (ppm), equivalent to an average daily dose of 0, 35, 65 or 110 mg/kg bw, for males and 0, 125, 250 or 500 ppm [mg/L], equivalent to an average daily dose of 15, 25 or 70 mg/kg bw, for females for 104 weeks (males) or 105 weeks (females). Mean body weights of males were similar to those of the controls; mean body weights of 250- and 500-ppm females were lower than those of controls from weeks 89 and 73, respectively. Survival of exposed males and females was similar to that of the controls. Statistical analyses were carried out using the Poly-3 test. Hepatocellular adenomas occurred at an increased incidence in males: 29/50, 40/50 (p = 0.003), 34/49 and 39/50 (p = 0.011) in control, low-, mid- and high-dose mice, respectively. The incidence of hepatocellular carcinomas in males was: 15/50 control, 35/50 low-dose, 41/49 mid-dose and 40/50 high-dose mice, respectively (p < 0.001, pairwise comparisons for all treated groups). The incidence of hepatoblastomas in males was: 2/50, 18/50, 22/49 and 15/50 (p < 0.001, pairwise comparisons for all treated groups) in control, low-dose, mid-dose and high-dose mice, respectively. In female mice, the incidence of hepatocellular carcinomas was increased in a dose-related manner: 13/49 control, 23/50 low-dose, 33/50 (p = 0.014) mid-dose and 41/50 high-dose mice (p < 0.001). The incidence of hepatoblastomas was also significantly increased: 1/49 control, 2/50 low-dose, 9/50 (p = 0.007) mid-dose and 16/50 high-dose mice (p < 0.001) (National Toxicology Program, 1997).

3.1.2. Rat

Groups of 50 male and 50 female Fischer 344/N rats, eight weeks of age, were given drinking-water containing 0, 100, 200 or 400 ppm pyridine (purity, 99.8%) for 103 weeks (males) or 104 weeks (females). Average daily doses were 0, 7, 14 and 33 mg/kg bw. Mean body weights of 200- and 400-ppm males after weeks 73 and 6, respectively, and females after weeks 61 and 9, respectively, were less than those of controls [statistical significance not reported]. Survival of exposed males and females was not significantly different from that of controls. As shown in Table 3, the incidence of renal tubule adenomas in male rats was increased, whether single sections or single and multiple sections combined were evaluated (National Toxicology Program, 1997).

Table 3

Incidence of renal tubule tumours in male Fischer 344 rats fed pyridine in the diet.

In a concurrent experiment, groups of 50 male Wistar rats, seven weeks of age, were given drinking-water containing 0, 100, 200 or 400 ppm pyridine (purity, 99.8–0.6%), resulting in average daily doses of approximately 8, 17 or 36 mg/kg bw, for 104 weeks. Mean body weights of rats exposed to 100, 200 or 400 ppm were significantly lower than those of controls, beginning at weeks 69, 49 and 6, respectively. Survival of rats exposed to 200 or 400 ppm pyridine was significantly lower than that of the controls. The incidence of testicular adenoma in rats exposed to 400 ppm was significantly increased compared with controls: 5/50 controls, 6/49 low-dose, 4/49 mid-dose and 12/50 high-dose (p = 0.012, pairwise comparison). In contrast to the Fischer rats, renal tubule cell tumours were not observed at increased incidence, even after step sectioning (US National Toxicology Program, 1997). [The Working Group noted that the National Toxicology Program cited a historical control range for testicular adenomas in Wistar rats (0–22%) (Walsh & Poteracki, 1994), the upper limit of which was similar to the incidence in high-dose males seen in this study.]

4.1.1. Humans

The fate of pyridine was examined in two healthy male subjects, who each received an oral dose of 3.4 mg [¹⁴C]pyridine [approx. 0.01 mg/kg bw] in orange juice. A total of 65 and 68% of the ¹⁴C-dose was recovered in the 0–24-h urine of the two subjects, respectively, and two metabolites were identified: pyridine N-oxide, which accounted for 32% of the dose, and N-methylpyridinium ion, accounting for 6 and 12% of the dose, respectively. Some 25% of the dose was not characterized (D'Souza et al., 1980; Damani et al., 1982).

4.1.2. Experimental systems

Pyridine is metabolized in animals by oxidation at the nitrogen atom, giving pyridine N-oxide, and at all carbon atoms of the ring, giving 2- and 4-pyridone and 3hydroxypyridine. In addition, it undergoes N-methylation, yielding the quaternary ammonium ion N-methylpyridinium. The relative contributions of these pathways to the overall fate of pyridine were examined by Damani et al. (1982) who administered [¹⁴C]pyridine intraperitoneally to rats, mice, guinea-pigs, hamsters, gerbils, rabbits and cats at a dose of 7 mg/kg bw. At least 50% of the administered ¹⁴C was recovered in the urine of the animals and the amounts of the various specific metabolites differed markedly between species, as shown in Table 4. Only small amounts (0.4–5% of dose) of unchanged pyridine were found in most species, but cats excreted 14% and rabbits 25% of the dose in this form. The extent of N-oxidation varied widely between species, from 0.3% of dose in rats to 39% in hamsters. Pyridine N-oxide was not detected in rabbit urine. The excretion of N-methylpyridinium also varied between species, being lowest in gerbils (∼2% of dose) and highest in cats (51% of dose). The major C-oxidation product was 4-pyridone, which ranged from 4% of the dose in hamsters to 19% in rabbits. 2-Pyridone and 3-hydroxypyridine were minor metabolites in all species, the former being absent from the metabolic profile in rabbits. Mice did not oxidize pyridine at any carbon atom of the ring. The occurrence of additional metabolic pathways is suggested by the excretion of unidentified products, accounting for up to 37% of the dose, in all species except guinea-pigs and cats (Damani et al., 1982). These pathways include glucuronidation of 3-hydroxypyridine, previously observed in rabbits (Smith, 1953).

Table 4

Species variations in the metabolic C- and N-oxidation and N-methylation of [¹⁴C]pyridine in various laboratory animals in vivo.

There is a dose-dependence in the metabolism of pyridine. At low doses of pyridine, N-methylation may be the preferred route of biotransformation, while at higher doses, such as 40 mg/kg bw, the extent of N-oxidation varied from some 10% in rats to 20–40% in mice, hamsters, guinea-pigs, rabbits and ferrets (Damani et al., 1982). In rats, the formation of N-methylpyridinium ion as a percentage of administered dose fell from 10 to 0.8% with increasing dose over the range 1–500 mg/kg bw (D'Souza et al., 1980). The occurrence of N-methylation was similar whether pyridine was given orally or by intraperitoneal injection. In contrast, guinea-pigs excreted 31% of a dose as N-methylpyridinium independently of dose (either 1 or 7 mg/kg bw, as for rats): this was unaffected by the route of administration but the excretion decreased to 2% when the intraperitoneal dose was 500 mg/kg bw. The low N-methylation capacity of the rat was not enhanced by pre-treatment and dietary supplementation with DL-methionine, the precursor of the methyl donor S-adenosylmethionine.

D'Souza et al. (1980) examined the further metabolism of N-methylpyridinium. Rats and guinea-pigs given N-methyl[¹⁴C]pyridinium by intraperitoneal injection excreted 53% and 85% respectively of the dose in the 0–24-h urine. In both species, > 95% of urinary ¹⁴C was present as unchanged N-methylpyridinium.

4.2.1. Humans

Ingestion of approximately 500 mg/kg bw pyridine by a 29-year-old man caused nausea, dizziness, abdominal pain and lung congestion followed by death after 43 h. Inhalation by workers of pyridine vapours at a concentration of about 125 ppm [405 mg/m³] pyridine for 4 h per day for one to two weeks resulted in headache, dizziness, insomnia, nausea and anorexia (Jori et al., 1983).

4.2.2. Experimental systems

Pyridine citrate given in the diet (0.7–1.0%) to young adult male rats [strain not stated] resulted in the death of most of the animals within two or three weeks (Baxter, 1947). Clinical and histopathological examination revealed acute hepatic and renal injury, followed by regenerative changes, cirrhosis and chronic renal injury. Increasing the choline content of the diet at the same time that the pyridine level was also being increased caused a marked reduction in fatty degeneration and fibrosis of the liver without any significant reduction in the severity and extent of the acute necrosis.

In rats, the LD₅₀ of pyridine after a single subcutaneous injection was estimated to be 866 mg/kg bw (Mason et al., 1971). It is of interest to note that the intraperitoneal LD₅₀ of N-methylpyridinium, a major metabolite in some species, is 0.22 g/kg bw in mice, compared with 1.2 g/kg bw for pyridine (D'Souza et al., 1980). A dose of 100 mg/kg bw administered subcutaneously twice weekly for one year to male and female Fischer 344 rats led to significant retardation of weight gain (Mason et al., 1971). Inhalation of 5 ppm [16 mg/m³] pyridine for 6 h per day for four days caused olfactory epithelial lesions in male Fischer 344/N rats. These included vascular degeneration of sustentacular cells, focal, marked attenuation of the epithelium, loss of neurons and the presence of intraepithelial luminal structures (Nikula & Lewis, 1994). In male Sprague-Dawley rats, a single intraperitoneal dose of pyridine (200 mg/mL saline; 1 mmol/kg bw) caused a significant increase in serum level of sorbitol dehydrogenase, indicating liver damage (Felten et al., 1998).

In male New Zealand White rabbits, pyridine treatment (one intraperitoneal injection of 100 mg/kg bw daily for five days) resulted in increased hepatic microsomal content of cytochrome P450, with induction of several isoforms that exhibit elevated catalytic activities toward pyridine, N-nitrosodimethylamine, alcohols and aniline (Kaul & Novak, 1987). Kim et al. (1988) confirmed these findings, demonstrating the induction of a high-affinity isozyme [subsequently understood to be CYP2E1] responsible for the production of pyridine N-oxide. Treatment of male Sprague-Dawley rats with pyridine as a single intraperitoneal dose of 100 mg/kg bw resulted in moderate induction of hepatic CYP1A1, as judged by inspection of immunoblots (not quantified) (Kim et al., 1991a). Similar results were obtained for renal CYP1A1 and CYP1A2 (Kim et al., 1995). Combined treatment of male Sprague-Dawley rats with pyridine and acetone had over-additive (synergistic) inducing effects on CYP1A1 and CYP1A2 in the liver and CYP1A1 in the lung, where the effect was particularly great. Thus, lung CYP1A1 activity was increased 21-fold by exposure to 20 ppm [65 mg/m³] pyridine vapour (5–6 h per day for 10 consecutive days), fivefold by oral intake of acetone (7.5% v/v solution in drinking water for 10 consecutive days) and 115.5-fold by the combined treatment (Iba et al., 1993). Other isozymes inducible in rat liver (male Sprague-Dawley) by pyridine treatment are CYP2B1/2B2 and, most notably, CYP2E1 (Kim et al., 1993), while in rabbit liver (male New Zealand White) an increase in CYP2E1 but no increase in CYP2B and only a marginal increase in CYP4B expression was observed (Kim et al., 1991b). In SENCAR mouse skin, topical application of pyridine (300 or 500 mg/kg bw) resulted in increases in CYP1A1, CYP2B1 and CYP3A (Agarwal et al., 1994).

In inhalation experiments in male Fischer 344/N rats, exposure to 5 ppm pyridine for four days (6 h per day) resulted in induction of hepatic CYP2E1 (Hotchkiss et al., 1993). Induction of hepatic CYP2E1 was also observed in male Swiss albino mice and male Sprague-Dawley rats treated daily with 80 mg/kg bw pyridine (given intraperitoneally) for one to three days (Anari et al., 1995). In pyridine-treated male Sprague-Dawley rats (one dose of 100 mg/kg bw, daily for four days), increased CYP2E1 protein was observed in the liver and kidney, while CYP2E1 mRNA was induced only in the kidney, indicating tissue-specific mechanisms of induction (Goasduff et al., 1996). Another enzyme inducible by pyridine is carboxylesterase. Inhalation of 5 ppm pyridine for four days (6 h per day) resulted in increased carboxylesterase immunoreactivity in Bowman's glands and sustentacular cells of the nasal mucosa in male Fischer 344/N rats, 20 hours after the end of exposure (Nikula et al., 1995). In primary cultures of hepatocytes from male Sprague-Dawley rats treated with 25 mM [2 g/L] pyridine for 24 h, the CYP2E1 protein level was increased by about ninefold, and that of CYP2B mRNA and protein by about 30-fold (Zangar et al., 1995).

Acute pyridine treatment (single intraperitoneal dose of 200 mg/kg bw) increased the metabolism of 2-butanol twofold in Sprague-Dawley rat liver microsomes and threefold in rabbit (New Zealand White) liver microsomes (Page & Carlson, 1993). In liver microsomes from pyridine-treated (one intraperitoneal injection of 100 mg/kg bw, daily for four days) male Sprague-Dawley rats, increased oxidative biotransformation of the chlorofluorocarbon 1,2-dichloro-1,1,2-trifluoroethane was found the day after the last injection (Dekant et al., 1995).

In male Sprague-Dawley rats, a single intraperitoneal treatment with pyridine (100 mg/kg bw) enhanced the metabolic activation of carbon tetrachloride 24 h later, leading to increased hepatic expression of the immediate early genes c-fos and c-jun (Gruebele et al., 1996). Similarly, pyridine treatment (a single intraperitoneal dose of 200 mg/kg bw) of male NSA and CD1 mice resulted in enhanced formation of styrene oxide (S enantiomer) from styrene in liver microsomes 18 h after dosing (Carlson, 1997). In agreement with these results, Gadberry et al. (1996) reported enhanced hepato- and pneumotoxicity of styrene in male non-Swiss albino mice treated with pyridine. Induction of CYP2E1, after a single intraperitoneal dose of pyridine (200 mg/kg bw) given to male Sprague-Dawley rats, was correlated with increases in para-nitrophenol hydroxylation, ethoxyresorufin deethylation and N-nitrosodimethylamine metabolism in lung and liver microsomes 24 h after dosing (Carlson & Day, 1992). Treatment of Sprague-Dawley rats by intraperitoneal injection with 100 mg/kg bw pyridine per day for three days led to a threefold increase in testicular microsomal CYP2E1 content and para-nitrophenol hydroxylation (Jiang et al., 1998).

Male and female Fischer 344 rats and B6C3F1 mice and male Wistar rats were given drinking water containing 0, 50, 100, 250, 500 or 1000 ppm (mg/L) pyridine for 13 weeks (National Toxicology Program, 1997). Water consumption by female Fischer 344 rats and male Wistar rats exposed to 1000 ppm pyridine was lower than that of control rats. Evidence of anaemia was present in male and female Fischer 344 rats. Exposure to pyridine (500 or 1000 ppm) increased serum alanine aminotransferase and sorbitol dehydrogenase activities and the incidence of centrilobular degeneration, hypertrophy, chronic inflammation and pigmentation in all rats. Spontaneous nephropathy, common in ageing male rats, increased only in male Fischer 344 rats exposed to 500 or 1000 ppm pyridine. The incidence of granular casts and renal tubule hyaline degeneration was increased in male Fischer 344 rats exposed to 500 or 1000 ppm pyridine. Immunohistochemical staining for α_2u-globulin was positive in all male rats and negative in female Fischer 344 rats [actual data not reported]. In mice, no treatment-related clinical findings were observed.

Male and female Fischer 344 rats and male Wistar rats were given drinking water containing 0, 100, 200 or 400 ppm (mg/L) pyridine for 103–104 weeks (National Toxicology Program, 1997). Male B6C3F₁ mice were given drinking water containing 0, 250, 500 or 1000 ppm pyridine for 104 weeks and female B6C3F₁ mice 0, 125, 250 or 500 ppm pyridine for 105 weeks. In Fischer 344 rats, the incidence of renal tubule hyperplasia was increased in males exposed to 400 ppm pyridine compared with controls; the severity of chronic progressive nephropathy was increased slightly in males with increasing exposure concentration, but statistical significance was not indicated; the incidence of mineralization of the stomach in the high-dose males was increased significantly compared with controls; increases in centrilobular cytomegaly and cytoplasmic vacuolization, and pigmentation in the liver were seen in male and females; periportal fibrosis was increased in the liver of males, with an increased incidence of bile duct hyperplasia in females. In male Wistar rats, liver lesions included an increase in the incidence of centrilobular degeneration and necrosis, fibrosis, periportal fibrosis, and pigmentation. Spontaneous, age-related chronic progressive nephropathy was moderately severe in control and exposed male Wistar rats and was considered to be the cause of the high mortality in this study. In mice, pyridine increased the incidence of haematopoietic cell proliferation in the spleen and follicular cell hyperplasia in the thyroid gland.

Incubation in 1–20 µM pyridine for 20 min inhibited norepinephrine-induced phasic and tonic contractions in the thoracic aorta, incubated as aortic rings, as well as the endothelium-denuded aorta of Wistar rats (Hsu & Lin-Shiau, 1995). These effects were related to inhibition of the calcium influx normally elicited by norepinephrine.

4.3.1. Humans

No data were available to the Working Group.

4.3.2. Experimental systems

Groups of 10 male and 10 female B6C3F₁ mice were exposed to 0, 250, 500 or 1000 ppm (mg/L) pyridine in the drinking-water for 13 weeks. Average daily doses were 0, 50, 85 and 160 mg/kg bw for males and 0, 60, 100 and 190 mg/kg bw for females. Spermatozoal motility was slightly, but significantly, decreased at all three dose levels tested. There were no significant differences in estrous cycle lengths in females (National Toxicology Program, 1997).

Groups of 10 male and 10 female Fischer 344 rats were exposed to 0, 250, 500 and 1000 ppm pyridine in the drinking-water for 13 weeks. Average daily doses were 0, 25, 55 and 90 mg/kg bw. At the highest dose level, a lower body weight was accompanied by reduced weight of epididymis and testes in males. In females, average estrous cycle length was significantly increased at the highest dose level (National Toxicology Program, 1997).

4.4.1. Humans

No data were available to the Working Group.

4.4.2. Experimental systems (see Table 5 for references)

Table 5

Genetic and related effects of pyridine.

Ecotoxicological, including genetic toxicological, data have been reviewed by Jori et al. (1983) and the National Toxicology Program (1997).

Pyridine did not induce mutations in Salmonella typhimurium with or without metabolic activation, nor in mouse lymphoma L5178Y cells. It also gave negative results in chromosomal aberration assays in two Chinese hamster studies in vitro (one without an exogenous metabolic system only) and a mouse bone-marrow test in vivo, and in the sister chromatid exchange assay in Chinese hamster cells in vitro. The invivo mouse micronucleus test was also negative. The cell transformation assay with Syrian hamster embryo cells (without exogenous metabolism only) was negative.

Pyridine lowered the clastogenicity of benzene but not of benzo[a]pyrene or cyclophosphamide in the in-vivo mouse bone marrow micronucleus test after oral administration (Harper et al., 1984; Harper & Legator, 1987).

Pyridine induced aneuploidy in Saccharomyces cerevisiae, when tested without metabolic activation only.

Three studies have been reported on the sex-linked recessive lethal mutation assay in Drosophila melanogaster. An equivocal result was obtained following feeding of pyridine, while a repeat test at a slightly higher concentration was negative; the injection method of treatment also gave a negative result. In another study, administration in the feed gave negative results, while injection gave positive results. The heritable translocation assay was negative in the same laboratory. A further set of experiments in the same laboratory produced negative results for the sex-linked recessive lethal test, although a lower dose for injection was used than in the other experiments.

Overall evaluation

Pyridine is not classifiable as to its carcinogenicity to humans (Group 3).