TOXICOLOGICAL PROFILE FOR 

PYRIDINE 

Agency for Toxic Substances and Disease Registry 

U.S. Public Health Service 

September 1992 
ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply 

endorsement by the Agency for Toxic Substances and Disease Registry. 










1 

1. PUBLIC HEALTH STATEMENT 

This Statement was prepared to give you information about pyridine and to emphasize the human 

health effects that may result from exposure to it. The Environmental Protection Agency (EPA) has 

identified 1,177 sites on its National Priorities List (NPL). Pyridine has been found at 4 of these sites. 

However, we do not know how many of the 1,177 NPL sites have been evaluated for pyridine. As EPA 

evaluates more sites, the number of sites at which pyridine is found may change. This information is 

important for you to know because pyridine may cause harmful health effects and because these sites 

are potential or actual sources of human exposure to pyridine. 

When a chemical is released from a large area, such as an industrial plant, or from a container, such 

as a drum or bottle, it enters the environment as a chemical emission. This emission, which is also 

called a release, does not always lead to exposure. You can be exposed to a chemical only when you 

come into contact with the chemical. You may be exposed to it in the environment by breathing, 

eating, or drinking substances containing the chemical or from skin contact with it. 

If you are exposed to a hazardous chemical such as pyridine, several factors will determine whether 

harmful health effects will occur and what the type and severity of those health effects will be. These 

factors include the dose (how much), the duration (how long), the route or pathway by which you are 

exposed (breathing, eating, drinking, or skin contact), the other chemicals to which you are exposed, 

and your individual characteristics such as age, sex, nutritional status, family traits, life style, and state 

of health. 

1.1 WHAT IS PYRIDINE? 

Pyridine is a flammable colorless liquid with an unpleasant smell. It can be made from crude coal 

tar or from other chemicals. Pyridine is used as a solvent and to make many different products such as 

medicines, vitamins, food flavorings, pesticides, paints, dyes, rubber products, adhesives, and 

waterproofing for fabrics. Pyridine can also be formed from the breakdown of many natural materials 

in the environment. Many of the foods that you eat have flavors that are the result of complex 

compounds that contain pyridine. 

Liquid pyridine evaporates into the air very easily. If pyridine is released to the air, it may take 

several months to years until it breaks down into other compounds. Pyridine also mixes very easily 

with water. If it is released to water or soil, it may break down in a few days to few months. 

You may find information on the properties and uses of pyridine and how it behaves in the 

environment in Chapters 3, 4, and 5. 

1.2 HOW MIGHT I BE EXPOSED TO PYRIDINE? 

Pyridine and pyridine-containing compounds are present throughout the environment at very low 

levels. Pyridine has been found in the air inside and 
2 

1. PUBLIC HEALTH STATEMENT 

around factories that produce it or use it to make other products. You could be exposed to pyridine if 

you work in one of these factories or if you live or work near a hazardous waste site that releases it to 

the surrounding air. Pyridine is also released into the air from burning cigarettes and from hot coffee. 

Pyridine is not usually found in rivers or other natural waters. It has been found in wells in an 

industrial area in Wyoming. The levels of pyridine in the well water were as high as 53 parts of 

pyridine in 1 billion parts of water (53 ppb). Pyridine is not usually found in the soil near hazardous 

waste sites or in industrial areas. Pyridine has been found in drinking water samples taken around 

hazardous waste sites and industrial areas. However, we do not know the levels. It is also found in 

certain foods such as fried chicken, cheese, and fried bacon. Although the levels in these foods are not 

known, they are probably very low and are not expected to result in any health effects. The level of 

pyridine in some frozen mango (a tropical fruit) was reported to be 1 part of pyridine per million parts 

of mango (1 ppm). You could be exposed to small amounts of pyridine if you eat these foods or drink 

water containing pyridine. 

You can find more information on how you might be exposed to pyridine in Chapter 5. 

1.3 HOW CAN PYRIDINE ENTER AND LEAVE MY BODY? 

Pyridine can enter your body when you breathe in air, drink water, or eat food that contains this 

chemical, or by skin contact with the chemical. When it enters your body by mouth, more than half of 

it is absorbed. Within 1 day, most of what was absorbed leaves your body in urine as pyridine itself or 

its breakdown products. We do not know what happens to the rest of it. There is also no information 

about what happens to pyridine that is breathed in or gets on your skin. 

You can find more information on how pyridine enters and leaves the body in Chapter 2. 

1.4 HOW CAN PYRIDINE AFFECT MY HEALTH? 

Very few studies have been conducted to determine the possible effects of pyridine exposure on 

human health. From case reports on humans and studies in animals, we think the most important health 

concern for humans exposed to pyridine will be damage to the liver. Other health concerns for humans 

may be neurological effects, renal effects, and irritation of the skin and eye. We do not know whether 

pyridine can cause cancer, birth defects, or problems with reproduction. 

You can find more information on health effects of pyridine in humans and animals in Chapter 

2. 
 

3 

1. PUBLIC HEALTH STATEMENT 

1.5	 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO PYRIDINE? 

Tests can be used to find out whether you have been recently exposed to pyridine. These tests 

measure levels of pyridine in urine and blood. They use special equipment and are done in special 

laboratories, so they are not usually available in a doctor's office. The levels of pyridine in urine or 

blood cannot be used, however, to find out how much pyridine you were exposed to or whether 

specific harmful effects will occur. 

You will find more information on how pyridine can be measured in exposed humans in 

Chapters 2 and 6. 

1.6 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government has set certain regulations and guidelines to help protect people from 

the possible health effects of pyridine in the environment. The EPA has not set limits on the amount of 

pyridine that may be present in drinking water. The Occupational Safety and Health Administration 

(OSHA) has set an average air exposure level of 5 ppm for an g-hour day, 40-hour work week. The 

National Institute for Occupational Safety and Health (NIOSH) has set 3,600 ppm in air as the level 

that is immediately dangerous to life and health (IDLH). The American Conference of Governmental 

Industrial Hygienists (ACGIH), which is a special nongovernment group set up to protect workers, also 

recommends 5 ppm for an g-hour day. 

You will find more information on governmental rules for pyridine in Chapter 7. 

1.7 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns not covered here, please contact your state health 

or environmental department or: 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology 

1600 Clifton Road, E-29 

Atlanta, Georgia 30333 

This agency can also provide you with information on the location of the nearest occupational 

and environmental health clinic. Such clinics specialize in recognizing, evaluating, and treating 

illnesses that result from exposure to hazardous substances. 

5 

2. HEALTH EFFECTS 

2.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, 

toxicologists, and other interested individuals and groups with an overall perspective of the toxicology 

of pyridine and a depiction of significant exposure levels associated with various adverse health 

effects. It contains descriptions and evaluations of studies and presents levels of significant exposure 

for pyridine based on toxicological studies and epidemiological investigations. 

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of exposure-­

inhalation, oral, and dermal--and then by health effect--death, systemic, immunological, neurological, 

developmental, reproductive, genotoxic, and carcinogenic effects. These data are discussed in terms of 

three exposure periods--acute (less than 15 days), intermediate (15-364 days), and chronic (365 days or 

more). 

Levels of significant exposure for each route and duration are presented in tables and illustrated 

in figures. The points in the figures showing noobserved-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the 

studies. LOAELs have been classified into "less serious" or "serious" effects, These distinctions are 

intended to help the users of the document identify the levels of exposure at which adverse health 

effects start to appear. They should also help to determine whether or not the effects vary with dose 

and/or duration, and place into perspective the possible 

significance of these effects to human health. 

The significance of the exposure levels shown in the tables and figures may differ depending 

on the user's perspective. For example, physicians concerned with the interpretation of clinical findings 

in exposed persons may be interested in levels of exposure associated with "serious" effects. Public 

health officials and project managers concerned with appropriate actions to take at hazardous waste 

sites may want information on levels of exposure associated with more subtle effects in humans or 

animals (LOAEL) or exposure levels below which no adverse effects (NOAEL) have been observed. 

Estimates of levels posing minimal risk to humans (Minimal Risk Levels, MRLs) may be of 

interest to health professionals and citizens alike. Estimates of exposure levels posing minimal risk to 

humans (MRLs) have been made, where data were believed reliable, for the most sensitive noncancer 

effect for each exposure duration. MRLs include adjustments to reflect human variability from 

laboratory animal data to humans. 
6 

2. HEALTH EFFECTS 

Although methods have been established to derive these levels (Barnes et al. 1988; EPA 1989a), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in 

development or are acquired following repeated acute insults, such as hypersensitivity reactions, 

asthma, or chronic bronchitis. As these kinds of health effects data become available and methods to 

assess levels of significant human exposure improve, these MRLs will be revised. 

2.2.1 Inhalation Exposure 

2.2.1.1 Death 

No studies were located regarding death in humans after inhalation exposure to pyridine. 

A l-hour LC50 for pyridine of 9,010 ppm for male rats and of 9,020 ppm for female rats was 

reported by Vernot et al. (1977). 

These l-hour LC50 levels for rats are recorded in Table 2-l and plotted 

in Figure 2-l. 

2.2.1.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, or dermal/ocular effects in humans or animals after inhalation exposure to 

pyridine. 

Renal Effects. No useful studies were located regarding renal effects in humans after 

inhalation exposure to pyridine. 

Rats exposed to pyridine vapors at 5-10 mg/L for a single exposure period of about 40 minutes 

showed a decrease in glutamine level in the kidneys accompanied by an increase in ammonia excretion 

in the urine (Bolonova 1972, as cited in EPA 1978). 

2.2.1.3 Immunological Effects 

No studies were located regarding immunological effects in humans or animals after inhalation 

exposure to pyridine. 


9 

2. HEALTH EFFECTS 

2.2.1.4 Neurological Effects 

There are limited studies regarding neurological effects in humans after inhalation exposure to 

pyridine. In a case report on healthy adults, symptoms that developed following exposure to 

undetermined levels of pyridine vapors included headaches, giddiness, a desire to sleep, and 

quickening of pulse and respiration (Neff 1886). The study did not describe the concentration of 

pyridine or other exposure conditions such as duration of exposure. 

No studies were located regarding neurological effects in animals after inhalation exposure to 

pyridine. 

No studies were located regarding the following health effects in humans or animals after 

inhalation exposure to pyridine: 

2.2.1.5 Developmental Effects 

2.2.1.6 Reproductive Effects 

2.2.1.7 Genotoxic Effects 

In vitro genotoxicity studies are discussed in Section 2.4. 

2.2.1.8 Cancer 

No studies were located regarding cancer effects in humans or animals after inhalation 

exposure to pyridine. 

2.2.2 Oral Exposure 

2.2.2.1 Death 

No useful studies were located regarding death in humans after oral exposure to pyridine. 

The death of a 32-year-old man who had been receiving pyridine as an intermittent medication 

for the treatment of epilepsy has been reported (Pollock et al. 1943). Because other medications such 

as magnesium sulfate, sodium bromide, phenobarbital, and/or sodium dilantin were stated to be 

previous and continuing medications for this patient and because the physical condition of this man at 

the start of pyridine treatment was not described, it is not possible to attribute this death specifically to 

pyridine exposure. 

Another case study reported the incident of a 29-year-old man who died within 2 days of 

ingesting approximately a half cup (about 125 mL) of pyridine during a syphoning accident (Helme 

1893). Upon admission to a hospital he was treated by the administration of demulcents (not otherwise 

described), milk, and brandy, application of mustard and linseed poultices to his throat and 
10 

2. HEALTH EFFECTS 

chest, and a brandy enema which he was reported to have retained. It is not clear whether this medical 

intervention was of benefit to this man or possibly exacerbated an already serious situation. 

An LD50 of 1,580 mg/kg was reported in rats within 14 days following a single oral 

administration of pyridine (Smyth et al. 1951). No compound related deaths were reported in rats that 

received pyridine by gavage for 90 days at dosage levels up to 50 mg/kg/day (Anderson 1987). 

The LD50 value for rats in the acute-duration category and a NOAEL and LOAEL for death in 

rats in the intermediate-duration category are recorded in Table 2-2 and plotted in Figure 2-2. 

2.2.2.2 Systemic Effects 

The NOAEL values and all reliable LOAEL values for each systemic effect in each species and 

duration category are recorded in Table 2-2 and plotted in Figure 2-2. 

Respiratory Effects. No studies were located regarding respiratory effects in humans after oral 

exposure to pyridine. 

No compound-related gross or histopathological effects were observed in the lungs of rats that 

received pyridine by gavage for 90 days at dosage levels up to 50 mg/kg/day (Anderson 1987). 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans 

after oral exposure to pyridine. 

No compound-related gross or histopathological effects were observed in the hearts of rats that 

received pyridine by gavage for 90 days at dosage levels up to 50 mg/kg/day (Anderson 1987). 

Gastrointestinal Effects. No studies were located regarding gastrointestinal effects in humans 

after oral exposure to pyridine. 

No compound-related gross or histopathological effects were observed in the gastrointestinal 

organs of rats that received pyridine by gavage for 90 days at levels up to 50 mg/kg/day (Anderson 

1987). 

Hematological Effects. No studies were located regarding hematological effects in humans 

after oral exposure to pyridine. 

No adverse effects on hematological parameters were noted in rats that received pyridine by 

gavage for 90 days at levels up to 50 mg/kg/day (Anderson 1987). 


13 

2. HEALTH EFFECTS 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans after 

oral exposure to pyridine. 

No compound-related gross or histopathological effects were observed in the muscles or bones 

of rats that received pyridine by gavage for 90 days at levels up to 50 mg/kg/day (Anderson 1987). 

Hepatic Effects. No reliable studies were located regarding hepatic effects in humans after oral 

exposure to pyridine. Case studies have been reported in which two patients with epilepsy developed 

hepatic effects when treated with pyridine (Pollock et al. 1943). Co-administration of other 

medications including magnesium sulfate, sodium bromide, phenobarbital, and/or sodium dilantin to 

these patients before and during pyridine administration and the lack of information on their hepatic 

status previous to pyridine administration preclude a clear understanding of the role of pyridine in the 

observed effects. 

Pyridine exposure has been associated with hepatic effects in rats. In a 90-day study, female 

rats that received pyridine by gavage at dosage levels of 10 mg/kg/day and higher had significantly 

increased liver weights (Anderson 1987). Inflammatory hepatic lesions were found in 70% of male rats 

that received 50 mg/kg/day. Lesions included bile ductule proliferation, mixed peribiliary infiltrate, 

and enlarged vacuolated hepatocytes. These lesions were reported in 20% of females at 50 mg/kg/day. 

The NOAEL for liver effects in this study was 1 mg/kg/day. In a 3-month drinking water study, mice 

that received pyridine at dosage levels up to 380 mg/kg/day did not have significantly increased levels 

of malondialdehyde (a measure of lipid peroxidation) in their livers (Pinsky and Bose 1988). Hepatic 

effects, including liver enlargeness, vacuolization, and necrosis were also reported in early studies in 

which pyridine citrate in diets was administered to male rats for up to 4 months in a complex series of 

dietary experiments (Baxter 1948; Coulson and Brazela 1948; Baxter and Mason 1947). However, due 

to extreme variations in the dietary sources of vital nutrients and the failure to describe in detail the 

effects of the diets alone (without pyridine) on the liver of these rats, it is difficult to clearly attribute 

the observed effects to pyridine exposure. 

Renal Effects. No reliable studies were located regarding renal effects in humans after oral 

exposure to pyridine. Renal effects have been reported in case studies in which patients with 

convulsive disorders were given pyridine in conjunction with other medications such as magnesium 

sulfate, sodium bromide, phenobarbital, and/or sodium dilantin (Pollock et al. 1943). Because of the 

coadministration of other substances and because the renal status of these patients before pyridine 

administration was not described, it is not possible to attribute the observed renal effects to pyridine. 
14
 

2. HEALTH EFFECTS 

No compound-related gross or histopathological effects were observed in the kidneys of rats 

that received pyridine by gavage for 90 days at dosage levels up to 50 mg/kg/day (Anderson 1987). 

Renal degeneration has been reported in studies in which pyridine citrate was administered in the diets 

of male rats for up to 4 months (Baxter 1948; Baxter and Mason 1947). However, despite variations in 

the composition of the diets and a lack of detailed information on the effects of those diets on the renal 

status of the test animals, it is possible to draw conclusions on the renal effects of pyridine 

administration from these studies. 

Dermal/Ocular Effects. No studies were located regarding dermal/ocular effects in humans 

after oral exposure to pyridine. However, congestion of the epiglottis, trachea, bronchi, lungs, 

esophagus, and stomach was reported in a case of accidental swallowing of half a cupful of pyridine 

which resulted in death (Helme 1893). This common finding of congestion would indicate that 

pyridine is irritating to mucous membranes of the gastrointestinal and respiratory systems. 

No compound-related dermal or ocular effects were observed in rats that received pyridine by 

gavage for 90 days at dosage levels up to 50 mg/kg/day (Anderson 1987). 

Other Systemic Effects. No studies were located regarding other systemic effects in humans 

after oral exposure to pyridine. 

In a go-day study, total body weight gain for male rats that received pyridine by gavage at 50 

mg/kg/day was significantly decreased from that of controls during weeks 8-12 of the study (Anderson 

1987). Significantly decreased weight gain was not found in any other dosage group. The NOAEL for 

this effect was 25 mg/kg/day. 

2.2.2.3 Immunological Effects 

No studies were located regarding immunological effects in humans or animals after oral 

exposure to pyridine. 

2.2.2.4 Neurological Effects 

No useful studies were located regarding neurological effects in humans after oral exposure to 

pyridine. A case study was reported in which a patient with epilepsy was reported to develop further 

neurological roblems, including a stuporous condition, slow and slurred speech, and slow reflexes 

during a 4-month oral treatment with pyridine as an anticonvulsive (Pollock et al. 1943). Coadministration of other medications, including magnesium sulfate, sodium bromide, phenobarbital 

and/or sodium dilantin to this patient before and during pyridine administration, compounded by the 

existing neurological disease state, preclude a clear understanding of the role of pyridine in the 

observed effects. 
15 

2. HEALTH EFFECTS 

No compound-related effects were observed in the brains of rats that received pyridine by 

gavage for 90 days at dosage levels up to 50 mg/kg/day (Anderson 1987). However, restlessness was 

observed in male rats following oral exposure at all dosage levels. 

In a 3-month drinking water study, mice that received pyridine at a dosage level of 380 mg/kg/day 

had significantly increased levels of malondialdehyde (a measure of lipid peroxidation) in the cerebellum 

and striatum of their brains (Pinsky and Bose 1988). A marked but nonsignificant increase was measured in 

the cortex. The NOAEL for these effects was 38 mg/kg/day. 

The NOAEL value for neurological effects in the rat in the intermediate-duration category is 

recorded in Table 2-2 and plotted in Figure 2-2. 

2.2.2.5 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after oral 

exposure to pyridine. 

2.2.2.6 Reproductive Effects 

No studies were located regarding reproductive effects in humans or animals after oral 

exposure to pyridine. 

2.2.2.7 Genotoxic Effects 

No studies were located regarding genotoxic effects in humans after oral exposure to pyridine. 

No chromosomal damage was observed in a micronucleus test in which mice were 

administered a single dose of pyridine by gavage at doses up to 1,000 mg/kg (Harper et al. 1984). 

Other genotoxicity studies are discussed in Section 2.4. 

2.2.2.8 Cancer 

No studies were located regarding cancer effects in humans or animals after oral exposure to 

pyridine. 

2.2.3 Dermal Exposure 

2.2.3.1 Death 

No studies were located regarding death in humans or animals after dermal exposure to 

pyridine. 
16
 

2. HEALTH EFFECTS
 

2.2.3.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, or other systemic effects in humans or animals after dermal exposure 

to pyridine. 

Dermal/ocular Effects. In primary skin irritation studies in rabbits, application of pure 

pyridine has resulted in mild dermal irritation (scored 3 out of a possible 10) and moderate ocular 

irritation (scored 7 out of a possible 10) (Smyth et al. 1951). 

No studies were located regarding the following health effects in humans or animals after 

dermal exposure to pyridine: 

2.2.3.3 Immunological Effects 

2.2.3.4 Neurological Effects 

2.2.3.5 Developmental Effects 

2.2.3.6 Reproductive Effects 

2.2.3.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.4. 

2.2.3.8 Cancer 

No studies were located regarding carcinogenic effects in humans or 

animals after dermal exposure to pyridine. 

2.2.4 Other Routes of Exposure 

Because the available data on the toxicity of pyridine via inhalation, oral, and dermal exposure 

are extremely limited, studies conducted via intraperitoneal and subcutaneous exposures have also 

been considered. These studies are also limited in number and scope, and serve only to provide 

additional evidence that decreased weight gain is associated with exposure to this chemical. 

2.2.4.1 Death 

Acute LD50 values for subcutaneously administered pyridine in rats have been reported as 

1,000 mg/kg (Brazda and Coulson 1946) and 866 mg/kg (Mason et al. 1971). An LD50 of 1,200 mg/kg 

was reported for mice that received pyridine via intraperitoneal injection (Baxter and Mason 1947). 

Mortality rates for rats that received subcutaneous injections of pyridine twice weekly for a 

year at levels up to 100 mg/kg/day were comparable to mortality rates of controls (Mason et al. 1971). 
17 

2. HEALTH EFFECTS 

2.2.4.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, or dermal/ocular effects in humans or animals after intraperitoneal or 

subcutaneous exposure to pyridine. 

Other Systemic Effects. No studies were located regarding other systemic effects in humans 

after intraperitoneal or subcutaneous exposure to pyridine. 

In rats that received subcutaneous injections of pyridine at 100 mg/kg/day twice weekly for a 

year, body weight was decreased 5%-16% below that of controls at the end of treatment. By 6 months 

after the termination of treatment, weights were comparable to control weights (Mason et al. 1971). 

2.2.4.3 Immunological Effects 

No studies were located regarding immunological effects in humans or animals after 

intraperitoneal or subcutaneous exposure to pyridine. 

2.2.4.4 Neurological Effects 

No studies were located regarding neurological effects in humans or animals after 

intraperitoneal or subcutaneous exposure to pyridine. 

2.2.4.5 Developmental Effects 

Abnormal chick development resulted from the injection of pyridine into eggs at very high 

levels (10 mg/egg or 20 mg/egg). Muscular hypoplasia occurred in 15% of chicks at the low dose and 

67% at the high dose. In addition, at the high dose, 4.9% of the chicks had defective beaks and 1.1% 

had short or twisted necks (Landauer and Salam 1974). 

2.2.4.6 Reproductive Effects 

No studies were located regarding reproductive effects in humans or animals after 

intraperitoneal or subcutaneous exposure to pyridine. 

2.2.4.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.4. 

2.2.4.8 Cancer 

No studies were located regarding cancer effects in humans after intraperitoneal or 

subcutaneous exposure to pyridine. 
18 

2. HEALTH EFFECTS 

There was no evidence of carcinogenicity due to pyridine administration in rats that received 

subcutaneous iniections at levels up to 100 mg/kg/day twice weekly for a year (Mason et al. 1971). 

2.3 TOXICOKINETICS 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

No studies were located regarding absorpt inhalation exposure to pyridine. ion in humans or 

anima1s after inhalation exposure to pyridine. 

2.3.1.2 Oral Exposure 

The available information indicates that orally administered pyridine is well absorbed by 

humans and animals. 

By 24 hours after ingestion of a single dose of 14C-pyridine at 0.05 mg/kg (administered in 

orange juice) by humans, approximately 67% of the administered 14C-label was recovered in the urine 

(D'Souza et al. 1980), indicating that at least 67% had been absorbed within that time period. In that 

same study, rats and guinea pigs that received 14C-pyridine at 7 mg/kg excreted 58% and 76%, 

respectively of the 14C-label in urine by 24 hours after administration, indicating absorption of at least 

those percentages of the administered dose. Rats administered 14C-pyridine at 7, 68, and 357 mg/kg 

excreted 58%, 13%, and 20%, respectively, of the 14C-label in their urine within 24 hours. The lower 

rate of excretion at higher doses suggests that the uptake of pyridine may involve nonlinear saturation 

kinetics. 

2.3.1.3 Dermal Exposure 

No studies were located regarding absorption in humans or animals after dermal exposure to 

pyridine. 

2.3.2 Distribution 

No quantitative studies were located regarding distribution in humans or animals after exposure 

to pyridine by the following routes: 

2.3.2.1 Inhalation Exposure 

2.3.2.2 Oral Exposure 

2.3.2.3 Dermal Exposure 
19 

2. HEALTH EFFECTS 

2.3.3 Metabolism 

Some information on the metabolism of pyridine is derived from a study in which the Nmethylpyridinium ion was identified as a urinary metabolite of 14C-pyridine administered orally to 

humans, rats, and guinea pigs and via intraperitoneal administration to rats, guinea pigs, gerbils, 

hamsters, rabbits, and cats (D'Souza et al. 1980). In the 24-hour urine collection in humans, this 

metabolite was present at 9% of the administered dose, and in other species, levels of Nmethylpyridinium varied widely with species, dose level, route of administration, and period of urine 

collection. Rats had a relatively low ability to methylate pyridine administered at 7 mg/kg either orally 

or via intraperitoneal injection, with 3.1% and 5.0%, respectively, of the administered dose recovered 

as the N-methylpyridinium ion in their urine in 24 hours. In guinea pigs, for comparison, these values 

were 31% and 31%, respectively, for oral and intraperitoneal administration. N-methylpyridinium 

appears to be more toxic to rats and mice than pyridine itself (Brazda and Coulson 1946). No attempts 

were made to identify other metabolites of pyridine in this study. However, a subsequent study 

identified pyridine-Noxide as a urinary metabolite of all species tested in that study except rabbits and 

as accounting for nearly one-third of the total radioactivity (32% of the administered dose) in the 24­

hour urine from the human volunteers in that study (Damani et al. 1982). Other pyridine metabolites 

determined in these test animals included 2-pyridone, 3-hydroxypyridine, and 4-pyridone (human urine 

was not analyzed for these metabolites). Pyridine-N-oxide was also identified in the urine of hamsters, 

mice, rats, rabbits, ferrets, and guinea pigs after intraperitoneal administration of pyridine (Gorrod and 

Damani 1980). In an analysis of the data on urinary metabolites of pyridine reported in the early 

literature, EPA (1978) and Santodonato et al. (1985) have proposed the metabolic pathway by which 

N-methylation followed by ring hydroxylation or, alternatively, ring hydroxylation in the meta position 

would account for the observed metabolites. The presence of the N-methylpyridinium ion has been 

reported in the urine of humans, rats, guinea pigs, gerbils, mice, hamsters, and cats (D'Souza et al. 

1980). However, this pathway does not take into account the identification of pyridine-N-oxide and 

other metabolites in the urine of several species (humans, hamsters, rats, rabbits, mice, ferrets, and 

guinea pigs) after oral or intraperitoneal administration of pyridine (Damani et al. 1982; Gorrod and 

Damani 1980). A proposed metabolic pathway incorporating all above metabolites for pyridine is 

shown in Figure 2-3. 

2.3.4 Excretion 

2.3.4.1 Inhalation Exposure 

No studies were located regarding excretion in humans or animals after inhalation exposure to 

pyridine. 

21
 

2. HEALTH EFFECTS
 

2.3.4.2 Oral Exposure 

The only available information on excretion of orally administered pyridine is a study by 

D'Souza et al. (1980). In two humans who received 14C-pyridine at 0.05 mg/kg (administered in orange 

juice), approximately 67% of the administered 14C-label was recovered in the urine in a 24-hour 

period. In rats and guinea pigs administered 7 mg/kg, recovery was approximately 58% and 76%, 

respectively. These data indicate that urine is the major route of pyridine excretion in these species at 

these dose levels. No other information was provided. 

2.3.4.3 Dermal Exposure 

No studies were located regarding excretion in humans or animals after dermal exposure to 

pyridine. 

2.3.4.4 Other Routes of Exposure 

No data are available on the excretion of pyridine administered to humans via other routes of 

exposure. Several animal species were given intraperitoneal injections of 14C-pyridine in a study by 

D'Souza et al. (1980). In rats, guinea pigs, gerbils, mice, hamsters, rabbits, and cats that received doses 

of 7 mg/kg, levels of 14C-label recovered in urine (48-hour collection in cats, 72 hours in rabbits, 24 

hours in all other species) ranged from 75% of the administered dose in cats to 48% in rats. 

Comparisons of 14C-label excretion in the urine of rats and guinea pigs that received the same 

dose (7 mg/kg) of 14C-pyridine via oral or intraperitoneal administration indicated that values within 

each species were similar for both routes of administration; in rats, these values were 58% and 48%, 

respectively, of the administered dose, and in guinea pigs, these values were 31% and 31%, 

respectively, of the administered dose for both routes. 

2.4 RELEVANCE TO PUBLIC HEALTH 

As discussed in Section 2.2, 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 MRLs can be 

derived. By the oral route, there is limited evidence from case studies in humans (Pollock et 

al. 1943) 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 
22 

2. HEALTH EFFECTS 

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. 

Death. No deaths that are clearly attributable to pyridine have been reported in humans. The 

available information in animals does not suggest that lethality is a public health concern for exposure 

to pyridine via inhalation or the oral route. 

The death of a 32-year-old man who had been receiving pyridine as an oral medication for a 

convulsive disorder (epilepsy) has been reported (Pollock et al. 1943). Because other medications such 

as magnesium sulfate, sodium bromide, phenobarbital, and/or sodium dilantin were stated to be 

previous and continuing medications for this patient and because the physical condition of this man at 

the start of pyridine treatment was not described, it is not possible to attribute this death specifically to 

pyridine exposure. 

In another case study, a 29-year-old man died within 2 days of swallowing an estimated halfcup of pyridine during a syphoning accident (Helme 1893). Medical intervention was immediate and 

rigorous and included the administration of demulcents (not otherwise described), milk, and brandy, 

application of mustard and linseed poultices to his throat and chest, and a brandy enema which he 

retained. It is not possible to assess the potential contribution of this treatment regimen to his rapid 

death. 

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. 

Systemic Effects. 

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, including bile duct proliferation, mixed peribiliary infiltrate, and enlarged vacuolated 

hepatocytes 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. However, preliminary 
23 

2. HEALTH EFFECTS 

evidence of hepatic effects from pyridine exposure has been previously reported in studies conducted 

more than 40 years ago. Pyridine citrate was administered to male rats (also Sprague-Dawley) for up to 

4 months in a complex series of dietary experiments that included variations in fat and carbohydrate 

sources and the levels of essential dietary nutrients such as certain amino acids (Baxter 1948; Baxter 

and Mason 1947; Coulson and Brazda 1948). The authors reported that the addition of pyridine to 

these diets resulted in hepatic enlargement, vacuolization, and necrosis. However, because of the other 

variations in the diet and lack of detail in reporting study results, it is difficult to interpret the findings 

of these experiments or to clearly attribute the observed effects to pyridine exposure. These studies do 

serve, however, to confirm the general conclusion of the Anderson (1987) study, which is that hepatic 

effects are of potential concern with oral exposure to pyridine and to suggest that exposed humans may 

also be at risk for hepatic effects. 

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 numbers of 

rats used per group and duration of exposure were not clearly reported. However, variations in dietary 

composition (i.e., source and percentage of vital nutrients) did not contribute to the appearance of the 

observed lesions. 

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. During weeks 8-12 of this study, male rats consistently weighed 12%-14% less than 

controls, a difference that was statistically as well as clinically significant. Food consumption was not 

decreased in treated animals of either sex. This observation is supported by the results of a l-year study 

in which the body weights of rats that were administered pyridine at doses up to 100 mg/kg/day via 

subcutaneous injection were decreased 5%-16% below control values (Mason et al. 1971). Although 

these observations suggest that effects on body weight might also pose a potential health concern for 

humans exposed to pyridine, it is important to note that they are based on limited evidence. 

Immunological Effects. There are no studies of immunological effects in humans or animals exposed 

to pyridine via any route of exposure. 
24 

2. HEALTH EFFECTS 

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). 

No morphological effects were noted in the brains of rats that received pyridine by gavage for 

90 days at dosage levels up to 50 mg/kg/day (Anderson 1987). However, restlessness was noted in the 

male rats of all groups which received pyridine. This neurological effect was not observed in controls 

or female test rats. Lipid peroxidation was observed in selected areas of the brain of mice that received 

pyridine in their drinking water for 3 months at a dosage level of 380 mg/kg/day (Pinsky and Bose 

1988). The authors suggest that lipid peroxidation could lead to regionally selective neurotoxicity. The 

significance of this observation in relation to neurological function and/or morphology is not entirely 

clear. However, there is some evidence that neurological effects resulting from pyridine exposure via 

the inhalation and oral routes of exposure may be health concerns. 

Developmental Effects. There are no studies of developmental effects in humans or animals 

exposed to pyridine via the inhalation, oral, or dermal routes. However, abnormal chick development 

resulted from injection of pyridine into eggs at very high levels (l0-20 mg/egg). Muscular hypoplasia 

occurred in 15% of chicks at the low dose and 67% at the high dose. In addition, at the high dose, 4.9% 

of the chicks had defective beaks and 1.1% had short or twisted necks (Landauer and Salam 1974). 

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 
25 

2. HEALTH EFFECTS 

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, presented in Table 2-3, 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. 

2.5 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. 

They have been classified as markers of exposure, markers of effect, and markers of susceptibility 

(NAS/NRC 1989). 

A biomarker of exposure is a xenobiotic substance or its metabolite(s) or the product of an 

interaction between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a 

compartment of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally 

the substance itself or substance-specific metabolites in readily obtainable body fluid(s) or excreta. 

However, several factors can confound the use and interpretation of biomarkers of exposure. The body 

burden of a substance may be the result of exposures from more than one source. The substance being 

measured may be a metabolite of another xenobiotic substance (e.g., high urinary levels of phenol can 

result from exposure to several different aromatic compounds). Depending on the properties of the 

substance (e.g., biologic half-life) and environmental conditions (e.g., duration and route of exposure), 

the substance and all of its metabolites may have left the body by the time biologic samples can be 

taken. It may be difficult to identify individuals exposed to hazardous substances that are commonly 

found in body tissues and fluids (e.g., essential mineral nutrients such as copper, zinc, and selenium). 

Biomarkers of exposure to pyridine are discussed in Section 2.5.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other 

alteration within an organism that, depending on magnitude, can be recognized as an established or 

potential health impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or 

cellular signals of tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in 

female genital epithelial cells), as well physiologic 

27 

2. HEALTH EFFECTS 

signs of dysfunction such as increased blood pressure or decreased lung capacity. Note that these 

markers are often not substance specific. They also may not be directly adverse, but can indicate 

potential health impairment (e.g., DNA adducts). Biomarkers of effects caused by pyridine are 

discussed in Section 2.5.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an 

organism's ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be 

an intrinsic genetic or other characteristic or a preexisting disease that results in an increase in 

absorbed dose, biologically effective dose, or target tissue response. If biomarkers of susceptibility 

exist, they are discussed in Section 2.7, "POPULATIONS THAT ARE UNUSUALLY 

SUSCEPTIBLE." 

2.5.1 Biomarkers Used to Identify and/or Quantify Exposure to Pyridine 

There is currently no biomarker that is used to identify or quantify exposure to pyridine. 

Pyridine can be measured in blood and urine in humans and animals by gas chromatography 

(Audunsson 1988; Dubowski 1975). Also the rate of urinary excretion levels of 14C-labelled pyridine 

(Shaker et al. 1982) and its metabolite, the N-methylpyridinuim ion, have been measured (D'Souza 

et al. 1980). However, these methods cannot be used to measure pyridine exposure in humans. 

Pyridine-N-oxide can also be identified in the urine of several species, including mice, rats, rabbits, 

hamsters, guinea pigs and ferrets after intraperitoneal exposure to pyridine (Gorrod and Damani 1980). 

However, based on the currently available information, the levels of these substances in biological 

media cannot be used to calculate or estimate corresponding levels of exposure to pyridine. 

2.5.2 Biomarkers Used to Characterize Effect Caused by Pyridine 

There are currently no subtle or sensitive biomarkers of effects associated with pyridine. 

Because of the limited amount of data available on this chemical, even the broad categories of toxicity 

have not yet been adequately characterized. 

2.6 INTERACTIONS WITH OTHER CHEMICALS 

There is currently no information on the interactions of pyridine with other chemicals. 

2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

No populations have been identified that are unusually susceptible to pyridine. However, 

persons with existing liver and kidney disease may be at increased risk of further liver and kidney 

damage, based on the results of studies in animals. 
28 

2. HEALTH EFFECTS 

2.8 MITIGATION OF EFFECTS
 

This section will describe clinical practice and research concerning methods for reducing toxic effects 

of exposure to pyridine. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to pyridine. When 

specific exposures have occurred, poison control centers and medical toxicologists should be consulted 

for medical advice. 

Central nervous system depression and hepatic and renal damage are the major effects observed 

following exposure to pyridine. Human exposure to pyridine may occur by inhalation, ingestion or by 

dermal contact. However, inhalation is the predominant route for acute exposures. General 

recommendations for reducing absorption of pyridine following exposure have included removing the 

exposed individual from the contaminated area and removing contaminated clothing, followed by 

washing the skin thoroughly with soap and water. If the eyes are exposed they are rinsed with water. 

Gastric lavage or administration of activated charcoal and a cathartic are common treatments following 

oral exposure (Spoerke 1991). Emetics are not recommended due to the hazard of aspirating gastric 

contents (Bronstein and Currance 1988). 

Information is limited regarding the retention of pyridine by the body, and so the need for methods for 

enhancing elimination is not clear. Excretion studies suggest that the compound is rapidly eliminated 

from the body (D'Souza et al. 1980). However, no information was located on the biological halflives 

of pyridine or its metabolites. No methods have been established for reducing the body burden 

following exposure to pyridine. 

The toxicity of pyridine has been attributed to its metabolites. If this is true, it could be possible to 

reduce toxicity by pharmacologically limiting metabolism, or shunting metabolism to routes that are 

less toxic than others. However, current knowledge of the metabolism of pyridine does not allow a full 

assessment of the net effect of interfering with that metabolism. Available studies suggest that 

methylation of pyridine may cause hepatic and renal injury by draining the labile methyl groups of 

choline and methionine thus producing an "intrinsic" deficiency of these substances (Baxter 1949; 

Baxter and Mason 1947). However, based on the metabolites found in urine in more recent excretion 

studies, methylation may not be a major metabolic route (D'Souza et al. 1980). Therefore, it's role in 

the overall toxicity of pyridine may be suspect. Urinary excretion of methylated pyridine accounted 

for only 5-12% of the administered dose in humans (D'Souza et al. 1980). On the other hand, urinary 

excretion of pyridine-N-oxide accounts for 32% of the administered dose, which is approximately half 

of the total radioactivity in the 24-hr urine from the human volunteers (Damani et al. 1982). The 

potential role of N-oxidation in the toxicity of pyridine has not been evaluated. Specific methods for 

reducing toxic effects cannot be established because of the limited information regarding the 

mechanisms of toxicity of pyridine. 
29 

2. HEALTH EFFECTS 

2.9 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in 

consultation with the Administrator of EPA and agencies and programs of the Public Health Service) 

to assess whether adequate information on the health effects of pyridine is available. Where adequate 

information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), 

is required to assure the initiation of a program of research designed to determine the health effects 

(and techniques for developing methods to determine such health effects) of pyridine. 

The following categories of possible data needs have been identified by a joint team of 

scientists from ATSDR, NTP, and EPA. They are defined as substance-specific informational needs 

that, if met, would reduce or eliminate the uncertainties of human health assessment. In the future, the 

identified data needs will be evaluated and prioritized, and a substance-specific research agenda will be 

proposed. 

2.9.1 Existing Information on Health Effects of Pyridine 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and 

animals to pyridine are summarized in Figure 2-4. The purpose of this figure is to illustrate the existing 

information concerning the health effects of pyridine. Each dot in the figure indicates that one or more 

studies provide information associated with that particular effect. The dot does not imply anything 

about the quality of the study or studies. Gaps in this figure should not be interpreted as "data needs" 

information (i.e., data gaps that must necessarily be filled). 

As shown in Figure 2-4, studies of human exposure to pyridine are limited to case reports in 

which systemic effects, neurological effects, and death were associated with oral exposure. Existing 

animal studies are limited to lethality determinations via the inhalation and oral routes, dermal and 

ocular irritation data, and information on systemic and neurological effects from an intermediateduration study via the oral route. 

2.9.2 Data Needs 

Acute-Duration Exposure. There are currently no useful data available on humans exposed to 

pyridine for this duration period for any route of exposure. The only information available for animals 

are inhalation LC50 and oral LD50 values in rats (Smyth et al. 1951; Vernot et al. 1977) and primary 

dermal and ocular irritation data in rabbits (Smyth et al. 1951). Data were 

31
 

2. HEALTH EFFECTS
 

not considered sufficient to derive an MRL for any route. Acute-duration studies conducted via the oral 

route would probably be most useful since persons living or working in the vicinity of hazardous waste 

sites are likely to be exposed via this route because pyridine has been found in the drinking water in 

these areas. Also, contamination of food and drinking water is possible in laboratories and industries 

where pyridine is being used. Inhalation data would also be useful for these populations and exposed 

workers. Toxicokinetic data are very limited for this chemical. A study using dermal exposure would 

be relevant to the safety of workers if absorption via this route were first demonstrated in other studies. 

Intermediate-Duration Exposure. There are currently no reliable data on humans exposed to 

pyridine for this duration period via any route of exposure. Data in animals are limited to a 90-day 

gavage study in rats in which the major adverse effects were hepatic lesions, neurological effects, and 

effects on weight gain were also seen (Anderson 1987). However, because there were no reliable 

supporting or confirmatory studies for this duration, the available data are not considered sufficient to 

derive an MRL for the oral or any other route. Toxicokinetic data are also extremely limited. An 

intermediateduration (90-day) study via the oral route would be useful since this is an important route 

of exposure for persons exposed via drinking water as a result of living or working in the vicinity of 

hazardous waste sites. The National Toxicology Program (NTP) is currently conducting a 14-week 

drinking water study in rodents (2 strains of rats and 1 strain of mice) which may provide valuable data 

to compare with information from the Anderson (1987) study which now serves as virtually the entire 

useful database for this duration period. A study conducted via dermal exposure would be especially 

useful if dermal absorption could first be demonstrated by other studies. 

Chronic-Duration Exposure and Cancer. There are no chronic-duration data available for 

humans or animals, and there are no toxicokinetic data for this exposure duration. Therefore, it is not 

possible to derive an MRL for any route for this duration. Chronic studies using the oral route would 

be useful, since chronic low-level exposure to pyridine via drinking water may occur in the vicinity of 

hazardous waste sites. Chronic inhalation studies are also necessary to characterize potential effects 

from breathing low levels of pyridine near these sites. 

There is also no information on the carcinogenic potential of pyridine in humans or animals. 

Chronic-duration studies conducted via any route of exposure should assess this potential effect. As 

stated previously, exposure via the oral route is probably the most relevant to persons living or 

working in the vicinity of hazardous waste sites. Inhalation exposure to pyridine in contaminated air is 

also a route of concern for persons living and working near these sites. 

Genotoxicity. The currently available in vivo and in vitro studies do not indicate that pyridine is 

potentially genotoxic (Abe and Sasaki 1977; Aeschbacher et al. 1989; Commoner 1976; Harper 
32 

2. HEALTH EFFECTS 

et al. 1984; Ishidate and Odashima 1977; Riebe et al. 1982; Seixas et al. 1982). Further studies in this 

area do not appear to be warranted unless metabolic studies indicate the generation of a potentially 

genotoxic metabolite, an alkylating agent, and/or 

a compound that might be capable of DNA binding. 

Reproductive Toxicity. There is currently no information on the effects of pyridine on 

reproductive parameters in humans or animals via any route of exposure. In any further studies 

conducted for any duration period and via any route of exposure, it would be useful to investigate the 

potential doseresponse relationship of exposure to pyridine on a number of end points, including sperm 

count, sperm morphology, and reproductive organ pathology. If the reproductive system were 

identified as a target, studies to assess reproductive function would be useful. This information would 

be valuable in helping to assess the impact of pyridine on the reproductive capacity of exposed workers 

and persons living and working in the vicinity of hazardous waste sites. 

Developmental Toxicity. There are currently no available studies on the developmental effects 

of pyridine via inhalation, oral, or dermal exposure in humans or animals. The relevance of effects 

observed on the development of chick embryos when extremely high levels of pyridine were injected 

into eggs (Landauer and Salam 1974) is unknown; these observations suggest that this may be an area 

in which further study is warranted. Studies to assess the potential developmental effects of exposure 

to pyridine would therefore, be useful. Chronic studies using the oral and inhalation routes would 

probably be the most helpful in assessing the potential risks to the offspring of persons exposed in the 

vicinity of hazardous waste sites. 

Immunotoxicity. There are currently no data in humans or animals on the effects of pyridine 

on the immune system via any route of exposure. Immunological assessments, including analysis of 

peripheral blood components and effects on lymphoid tissue, would be a valuable component of any 

intermediate- or chronic-duration studies conducted in the future via any route of exposure. This would 

be helpful in developing a dose-response relationship and assessing the potential risks of persons 

exposed in the workplace and in the vicinity of hazardous waste sites. 

Neurotoxicity. There are currently few data on the effects of pyridine on the nervous 

system of humans via any route of exposure. However, pyridine is a central nervous depressant 

and has been used to treat epileptic patients (Pollock et al. 1943). The only information in 

animals is a 90-day gavage study in rats (Pinsky and Bose 1988) in which no morphological 

effects were noted in brain tissue and a 3-month drinking water study in mice which resulted in 

increased levels of lipid peroxidation in brain tissue, Restlessness in male rats was observed in 

the 90 day gavage study (Anderson 1987). In any further studies conducted via any route of 

exposure for any duration period, it would be useful to collect data on any demonstrated 
33 

2. HEALTH EFFECTS 

neurological effects, including histopathological changes as well as clinical manifestations in order to 

assess the potential neurotoxic effects of exposure to pyridine in the workplace or in the vicinity of 

hazardous waste sites. A study currently being conducted by the firm of Arthur D. Little to assess the 

neurological effects of short-term oral exposure to pyridine in mice should provide useful information. 

Epidemiological and Human Dosimetry Studies. No epidemiological studies have been 

identified for populations exposed to pyridine. These studies would be useful in assessing potential 

adverse effects in humans. In any such studies, points of greatest interest based on the results of 

previous studies in animals appear to be effects on liver and body weight and any developmental 

abnormalities in the offspring of exposed persons. Neurological, dermal/ocular, and renal observations 

would also be of interest. Similarly, human dosimetry studies of these populations would be useful in 

associating pyridine levels with the reported effects. 

Biomarkers of Exposure and Effect. Measurement of pyridine or its metabolites, Nmethylpyridinium, or pyridine-N-oxide, in blood or urine may provide an adequate qualitative 

indication of recent exposure to pyridine (Audunsson 1988; Dubowski 1975; Gorrod and Damani 

1980). However, very little information is currently available on these measurements in humans or 

animals, especially for N-methylpyridinium. The development of methods that could be used to 

calculate or estimate levels of exposure to pyridine from the levels of these substances in biological 

fluids would be extremely useful. 

There are currently no subtle or sensitive biomarkers of effects known for pyridine. After 

pyridine toxicity has been more fully studied, further research to identify biomarkers of pyridine 

effects would be helpful in assessing possible health impacts of pyridine around hazardous waste sites. 

Absorption, Distribution, Metabolism, and Excretion. There is currently very little 

information on the toxicokinetics of pyridine. A study in humans, rats, and guinea pigs indicates that it 

can be absorbed by these species via the oral route (D'Souza et al. 1980). Estimates of the extent of 

absorption via the inhalation and dermal routes and calculations of the rates of absorption via all three 

routes would be useful in helping to compare relative potential risks due to the presence of pyridine in 

various environmental media. In addition, information on potential determinants of absorption (dose 

level, nutritional status, etc.) would also be helpful in assessing potential absorption by exposed 

humans and the consequent relevance of conducting further toxicity tests in animals by the inhalation 

or dermal routes. 

There are no distribution data available for pyridine in humans or animals. The use of multiple 

species and a comparison of tissue levels of pyridine associated with multiple dose levels via each 

route of exposure would be useful in helping to assess the likelihood that pyridine would reach 

potential target organs in exposed humans. 
34 

2. HEALTH EFFECTS 

It would be useful to fully elucidate the metabolic pathway for orally administered pyridine in 

mammalian species. Further studies via the oral route may provide data on potentially toxic 

intermediates, including evidence for the generation of alkylating agents. It would also be useful to 

collect data on urinary metabolites identified during inhalation or dermal administration of pyridine. 

Available data indicate that in humans, rats, and guinea pigs, orally administered pyridine 

and/or its metabolites are excreted mainly in the urine (D'Souza et al. 1980). However, complete 

balance studies to account for all of the pyridine administered are not available. Data on fecal and 

breath excretion associated with the oral route and with all routes of excretion after inhalation and 

dermal administration would be useful. 

Comparative Toxicokinetics. The toxicokinetic studies available in both humans and animals 

are limited and it is not possible to determine if there are any major differences in the kinetics of this 

compound across species. It would be useful to investigate patterns of distribution to identify target 

organs and to measure rates of excretion in several species and to identify blood metabolites in humans 

and animals in order to confirm these assumed relationships. Studies in this area would also be helpful 

in putting the results of all available toxicity studies into perspective in terms of their relevance to the 

potential human health effects of pyridine under similar conditions of exposure. 

Mitigation of Effects. Recommended methods for the mitigation of acute effects of pyridine 

include administration of oxygen if exposure is by inhalation, flushing with water if exposure is to skin 

or eyes, and gastric lavage or administration of activated charcoal if exposure is oral (Bronstein and 

Currance 1988; Spoerke 1991). No information was located concerning mitigation of effects from 

lower-level or longer-term exposure to pyridine. Further information on techniques to mitigate such 

effects would be useful in determining the safety and effectiveness of possible methods for treating 

pyridine-exposed populations surrounding hazardous waste sites. 

2.9.3 On-going Studies 

A research project is now in progress investigating the neurological effects of short-term 

exposure to pyridine via gavage in the rat (CCTTE 1988). These tests are being conducted by the firm 

of Arthur D. Little and are sponsored by EPA's Office of Solid Waste. No other details are currently 

available for this study. 

In addition, NTP is completing the prechronic phase of studies of pyridine (includes 14- and 

90-day studies). The objective of these studies is to determine doses for the chronic toxicity and 

carcinogenicity bioassay of pyridine in a 2-year drinking water study. Dr. June Dunnick is the NTP 
35 

3. CHEMICAL AND PHYSICAL INFORMATION 

3.1 CHEMICAL IDENTITY 

Table 3-1 lists common synonyms, trade names, and other pertinent identification information 

for pyridine. 

3.2 PHYSICAL AND CHEMICAL PROPERTIES 

Table 3-2 lists important physical and chemical properties of pyridine. 



39 

4. PRODUCTION, IMPORT, USE, AND DISPOSAL 

4.1 PRODUCTION 

Pyridine is produced either by isolation from natural sources such as coal, or through chemical 

synthesis (HSDB 1989). Pyridine is produced by the fractional distillation of coal-tar residues (HSDB 

1989; NSC 1978; Santodonato et al. 1985) in which 1 ton of coal produces 0.07-0.21 pounds of 

pyridine bases of which 57% is pyridine (Santodonato et al, 1985). Synthetically produced pyridine is 

currently the more important source of pyridine for commercial uses (Santodonato et al. 1985). Small 

amounts of pyridine are synthesized from acetaldehyde, formaldehyde, and ammonia with a fluidized 

silica-alumina catalyst, followed by fractionation to isolate the pyridine (Harper et al. 1985; HSDB 

1989; NSC 1978). 

Pyridine is produced from natural sources by Crowley Tar Products of Stow, Ohio, and 

Oklahoma City, Oklahoma (Harper et al. 1985; HSDB 1989; SRI 1986, 1987, 1988). Pyridine is 

synthetically produced by two companies, the Nepera Chemical Co. of Harriman, New York and the 

Reilly Tar and Chemical Corporation of Indianapolis, Indiana (Harper et al. 1985; SRI 1986, 1987, 

1988). 

Current volumes of pyridine produced in the United States were not located (HSDB 1989). 

Production volumes steadily increased from 1945 (844 metric tons) through 1968 (3,366 metric tons), 

and the estimated 1985 production volume of pyridine was 6,800 metric tons (Santodonato et a1. 

1985). Production is expected to continue at a steady annual increase of l-28 depending upon economic 

conditions (Santodonato et al. 1985). The U.S. production capacity for synthetic pyridines (pyridine 

and pyridine derivatives) is estimated to be 27,216 metric tons (Santodonato et al. 1985). 

Harper et al. (1985) estimated the 1982 consumption of pyridine in the United States at 5,400-7,500 

metric tons. Facilities that manufacture or process pyridine are shown in Table 4-l. 

4.2 IMPORT/EXPORT 

No information was located regarding the current import volume of pyridine. The 1973 import 

volume was 4.5 metric tons (HSDB 1989). The United States exports 50% of the pyridines it produces 

(Harper et al. 1985). It is not clear whether this includes pyridine derivatives in addition to pyridine. 

In 1975, exports of pyridine were 341 metric tons (HSDB 1989). No data were located regarding 

current export volumes. 

4.3 USE 

Pyridine is used directly in the denaturation of alcohol (ACGIH 1986; HSDB 1989; NSC 1978) 

and as a solvent in paint and rubber preparation (ACGIH 1986; HSDB 1989; NSC 1978) and in research 

laboratories for functions such as extracting plant hormones (Santodonato et al. 1985). Half of the pyridine 

41 

4. PRODUCTION, IMPORT, USE, AND DISPOSAL 

produced today is used as an intermediate in making various insecticides and herbicides for 

agricultural applications (ACGIH 1986; Harper et al. 1985; Santodonato et al. 1985). Approximately 

20% goes into the production of piperidine (Harper et al. 1985; Santodonato et al. 1985) which is 

commercially significant in the preparation of chemicals used in rubber vulcanization and 

agriculture (NSC 1978). Pyridine is also used as an intermediate in the preparation of drugs 

(antihistamines, steroids, sulfa-type and other antibacterial agents) dyes, water repellents, and 

polycarbonate resins (ACGIH 1986; Harper et al. 1985; NSC 1978; Santodonato et al. 1985). Pyridine 

is also approved by the Food and Drug Administration (FDA) for use as a flavoring agent in the 

preparation of foods (Harper et al. 1985; HSDB 1989) (for additional information about pyridine in 

foods, see Chapter 5). 

4.4 DISPOSAL 

Waste pyridine, when present as a constituent of a commercial chemical product or chemical 

intermediate, is considered to be a hazardous waste, as is any residue, soil, water, or other debris 

resulting from the clean-up of this waste. Disposal of these materials must be managed according to 

state and federal regulations (HSDB 1989). Restrictions that apply to the disposal of waste pyridine are 

listed in Chapter 7. 

Current practices for the disposal of waste pyridine include rotary kiln incineration at 820°­

1,600°C (HSDB 1989). Waste pyridine is a potential candidate for liquid injection incineration (650° ­

1,600°C) or fluidized bed incineration at a temperature range of 450°-980°C (HSDB 1989). 

43 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW
 

Pyridine is an organic liquid with an unpleasant odor; it is very soluble in water. It is released 

to the environment from industrial sources that manufacture and use it and as fugitive emissions from 

facilities such as coal gasification and oil shale processing. Pyridine may be removed from the 

atmosphere by photooxidation or wet deposition (precipitation). Pyridine in water is unlikely to 

volatilize appreciably, but may sorb to soils and sediments or biodegrade. Bioconcentration of pyridine 

in aquatic organisms is not likely to be important. 

Pyridine has rarely been detected in ambient air, water, or soil, except in the vicinity of 

industrial sources. Several foods may contain pyridine, and ingestion of these foods is the most likely 

route of pyridine exposure for the general population. Occupational exposure to pyridine may be high. 

Populations living in the vicinity of hazardous waste sites where pyridine has been detected may also 

be exposed. The EPA has identified 1,177 NPL sites. Pyridine has been found at 4 of the sites 

evaluated for this chemical. However, we do not know how many of the 1,177 NPL sites have been 

evaluated for this chemical. As more sites are evaluated by the EPA, the number may change (View 

1989). The frequency of these sites within the United States can be seen in Figure 5-l. 

5.2 RELEASES TO THE ENVIRONMENT

 Manufacturers, processors, and users of pyridine are required to report quantities of releases of 

this substance to environmental media annually (EPA 1988a). According to the SARA Section 313 

Toxics Release Inventory (TRI), an estimated total of 635,374 pounds of pyridine were released to the 

environment from manufacturing and processing facilities in the United States in 1987 (TRI 1989). 

The TRI data should be used with caution since the 1987 data represent first-time reporting by these 

facilities. Only certain types of facilities were required to report. This is not an exhaustive list. The 28 

facilities reporting releases in 1987 are presented in Table 5-l. 

Additional releases of pyridine may occur from oil shale processing and coke oven facilities, 

but these releases are not included in the TRI. Releases of pyridine relevant to specific media are 

discussed below. 

5.2.1 Air 

Pyridine is released to the atmosphere from facilities that manufacture and use this compound 

and from oil shale processing and coke oven facilities. Releases of an estimated 298,438 pounds of 

pyridine to air from domestic industrial sources were reported in 1987 (TRI 1989). Atmospheric 

emissions of pyridine from shale oil waste waters ranged from 0.44 to 30 μg/mL of wastewater 

(Hawthorne and Sievers 1984). 


46
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.2.2 Water 

Releases of pyridine to ambient waters have been reported. Industrial releases to surface water 

and groundwater (underground injection) reported in 1987 were estimated to be 4,630 pounds and 

303,650 pounds, respectively (TRI 1989). In addition, 209,880 pounds of pyridine were disposed of in 

publicly owned treatment works (POTWs) in 1987 (TRI 1989). Some fraction of the quantity treated at 

POTWs is probably released to the environment. Pyridine was detected in one of two oi1 shale 

processing effluents at a concentration of 152 μg/L (ppb), but not in coal gasification plant effluents 

(Pellizzari et al. 1979). It was also detected in effluents from coke-oven quenching operations at 11 

mg/L (EPA 1982b) and detected, but not quantified, in four industrial effluents (Shackelford and Keith 

1976). Pyridine was also found in oil-shale retort water in Australia at a concentration of about 5 mg/L 

(Dobson et al. 1985). 

Data from the Contract Laboratory Program (CLP) Statistical Database indicate that none of 

the hazardous waste sites sampled were positive for pyridine in surface water or groundwater (Eckel 

1990). 

5.2.3 Soil 

Pyridine releases to land from industrial sources totalled an estimated 28,656 pounds in 1987 

(TRI 1989). Additional releases of pyridine to soil may occur from spillage of oil shale waste waters 

on land surfaces (Leenheer and Stuber 1981). No other information was located on pyridine releases to 

soil. Pyridine was not detected in soil samples from hazardous waste sites (Eckel 1990). 

5.3 ENVIRONMENTAL FATE 

5.3.1 Transport and Partitioning 

Pyridine exists in the atmosphere as a vapor. Its vapor pressure is approximately 0.027 atm 

(20.6 mmHg) at 25°C (Chao et al. 1983). Because of its high water solubility, a large fraction of vaporphase pyridine released to the atmosphere would tend to dissolve in water vapor (such as clouds and 

rain drops). A Henry's law constant estimates the tendency of a chemical to partition between its vapor 

state and water. The Henry's law constant for pyridine was measured as l.lxl0-5 atm-m3

-mole-1 at 25°C 

for aqueous solutions (5 mg/L) (Hawthorne et al. 1985). The magnitude of this value indicates that 

much of the pyridine in the atmosphere is removed by wet deposition (precipitation). 

Pyridine is highly soluble in water (Jori et al. 1983). The magnitude of Henry's law constant 

(l.lxl0-5 atm-m3-mole-1 for aqueous solutions) suggests that pyridine in water will not volatilize into the 

atmosphere quickly. In addition, the equilibrium partitioning of pyridine between water and air was 
47
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

found to be influenced by the pH of the water; a decrease in pH resulted in less partitioning from 

solution (Hakuta et al. 1977). The rate of pyridine volatilization from water has not been 

experimentally measured. 

Pyridine in water may partition to soils and sediments to an extent that depends on the pH of 

the water, and to a lesser extent, the organic-carbon content of the soil. Pyridine is a weak organic base 

in solution; its ionization constant is 5.23x10-6 at 20°C (Albert et al. 1948). Consequently, pyridine is 

predominantly in a cationic electrolyte form (pyridinium ion) in acidic solutions, whereas it is a neutral 

molecule in alkaline media. 

The extent of pyridine adsorption by pure-clay minerals was greatest in 

the pH range of 4-5.5, whereas adsorption was negligible in alkaline solutions (pH greater than 7) 

(Baker and Luh 1971). The magnitude of pyridinium adsorption was correlated with the cationexchange capacity of the clays. The rate of pyridinium desorption from the clays was slower than that 

of adsorption (Luh and Baker 1971). 

Pyridine was weakly adsorbed by sandstone at 38°C (Donaldson et al. 1975), but these authors 

did not report any pH measurements. Pyridine adsorption by an alkaline soil was negligible (Felice et 

al 1984); Zachara et al. (1987) also found that pyridine adsorption was more significant in acidic soils 

because of salt formation. 

The extent of adsorption of neutral organic molecules by soils is often correlated with the 

organic-carbon content of the soil (Hassett et al. 1983). When adsorption is expressed as a function of 

organic-carbon content, an organic carbon/water partition coefficient (Koc) can be calculated and may 

be used to classify the relative mobility of the chemical in soil. Based on its octanol-water partition 

coefficient (Table 3-2), an estimated Koc for pyridine is 7 (Roy and Griffin 1985). An experimentally 

derived Koc of about 40 can be calculated from the adsorption data in Zachara et al. (1987). As 

compared with Koc values listed for other compounds, these low Koc values suggest that pyridine is 

very highly mobile in soil, whereas pyridine as pyridinium will be less mobile, particularly in acidic 

soils. 

Pyridine may not partition to organisms in water. An octanol/water partition coefficient (KoW) 

estimates the likelihood of a chemical to partition to organisms in an aquatic environment. Octanol is 

believed to best imitate the fatty structures in plants and animal tissues (Kenaga and Goring 1980). The 

Koc of pyridine has been measured as 4 (Leo et al. 1971). This low value indicates that pyridine will 

not partition to fatty tissues in plants or animals. 

A bioconcentration factor (BCF) relates the concentration of a chemical in the tissues of aquatic 

organisms to the concentration of the chemical in the media in which they live. BCFs for pyridine have 

not been experimentally measured, but they may be less than 5, based on the empirical regressions of 
48
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

Kenaga (1980) and Neely et al. (1974). These low BCFs suggest that pyridine is probably not 

bioconcentrated by aquatic plants and animals and therefore probably not biomagnified in terrestrial or 

aquatic food chains. 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

Atmospheric pyridine may be slowly photodegraded by hydroxyl radicals in the troposphere. 

The rate constant for this reaction at 23°C has been measured as 5x10-13 cm3

/molecule-s, and the 

estimated atmospheric life time of pyridine may range from 23 to 46 days, depending on the 

concentration of hydroxyl radicals (Atkinson et al. 1987). Reaction by-products were not studied. It 

appears that the rate of ozone-initiated decay of pyridine is too slow to be an important mechanism for 

removing pyridine from the atmosphere. The decay rate of pyridine by ground-state oxygen (O(3P)) 

has been measured as 1.7x10-13 cm3/molecule-s (Mani and Sauer 1968). If the mean concentration of 

ground-state oxygen radicals is 5x10-4 molecules/cm3 (Cupitt 1980), then the half-life of this reaction 

(2.6 years) may also be too slow to be important. 

5.3.2.2 Water 

Biodegradation may be the most important mechanism that can degrade pyridine in water. 

Pyridine may oxidize in water, but the reactions are very slow. The rate constant for pyridine oxidation 

by alkylperoxy radicals (RO2) was estimated as approximately 0.67/M-s at 50°C (Mill et al. 1979). 

Because of the low concentration of these radicals in photolyzed natural waters, the half-life of this 

reaction may be on the order of decades. The rate constant for hydroxyl radical-initiated decay in water 

has been measured as 1.8x109/M-s at 21°C, pH 7 (Dorfman and Adams 1973). radicals is 10-17 mole/L 

(Mill et al. If the mean concentration of hydroxyl 1979), the half-life of this reaction would be about 

1.2 years. No information was located that suggests that pyridine hydrolyzes in water nor should it be 

anticipated from its chemical structure. 

Most pyridine biodegradation studies have been concerned with transformations in soils and 

sewage sludges (see Section 5.3.3). In a study of pyridine biodegradation in unfiltered river water, the 

rate of removal depended on the initial concentration of pyridine, but in general, at lower 

concentrations (less than 20 mg/L), pyridine degradation was virtually complete in 8 days or less 

(Cassidy et al. 1988). No information concerning the microorganisms present in the water was given, 

but this study suggests that biodegradation may be a much more rapid mechanism for the removal of 

pyridine from the environment than are abiotic mechanisms. 
49 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.3.2.3 Soil 

It is very likely that pyridine biodegrades in soils and sewage sludges, but the rate and extent of 

the process is uncertain. Pyridine has been found to biodegrade readily in laboratory-screening tests 

(Gerike and Fischer 1979, 1981; Ruffo et al. 1984). For example, about 94%-100% of the pyridine 

added to municipal wastewater biodegraded in 2-21 days, depending on the specific test procedure 

used. Other studies have reported that pyridine biodegraded in sewage water or sludge, but that the 

process was slow (Battersby and Wilson 1989; Cooper and Catchpole 1973; Ettinger et al. 1954; 

Gomolka and Gomolka 1978; Malaney 1960). For example, pyridine was found to be only partially 

degraded in dilute sewage sludge, and the process required a month before significant removal was 

detected (Battersby and Wilson 1989). 

There is evidence that pyridine can be biodegraded in soil. A branching bacteria 

(Proactinomyces) that can utilize pyridine as a sole-source of carbon and nitrogen, and energy has been 

isolated (Moore 1949). Pyridine was biodegraded in an aqueous extract of a garden soil, but the 

process was slow (Naik et al. 1972). Complete degradation under aerobic conditions required 

66-170 days, whereas l-2 months were required under anaerobic conditions. However, in a soil 

incubated with low concentrations of pyridine, the compound was completely degraded in about 8 days 

(Sims and Sommers 1985). The halflife of the process was approximately 3 days. 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

5.4.1 Air 

Pyridine has not been detected in ambient outdoor air, except in the vicinity of industrial 

sources. Pyridine was not found in rural or urban air (Hawthorne and Sievers 1984; Shah and 

Heyerdahl 1988). However, pyridine was detected at a concentration of 13 μg/m3

 in air in the vicinity 

of an oil shale wastewater facility (Hawthorne and Sievers 1984; Shah and Heyerdahl 1988). Pyridine 

was also present in indoor air at the same oil shale facility at a concentration of 41 μg/m3 (Hawthorne 

and Sievers 1984). The concentration of pyridine in indoor air contaminated with cigarette smoke may 

be as high as 16 μg/m3 (Brunnemann et al. 1991). 

Pyridine has been detected in workplace air at pyridine manufacturing plants and chemical 

plants using pyridine as an intermediate at time-weighted average (TWA) concentrations ranging from 

0.02 to 3.2 mg/m3 (EPA 1982b). 

5.4.2 Water 

Pyridine is rarely detected in ambient waters. It was present in surface water of the Cuyahoga 

River in Ohio (IJC 1983). The compound was not detected in groundwater samples in Wyoming 

(detection limit 0.1-0.5 ppb) (Pellizzari et al. 1979; Stuermer et al. 1982). However, it was detected in 
50 

5. POTENTIAL FOR HUMAN EXPOSURE 

groundwater 15 months after completion of coal gasification activities at a Wyoming site at 

concentrations ranging from 0.82 to 53 ppb (Stuermer et al. 1982). Pyridine was detected in 2 of 17 

drinking water concentrates (Lucas 1984). 

5.4.3 Soil 

No information was located on pyridine concentrations in ambient soils. Pyridine was detected 

in creosote-contaminated sediments in Puget Sound, Washington at a concentration of 0.22 μg/g 

(Krone et al. 1986). 

5.4.4 Other Environmental Media 

Pyridine may be present in foods from both natural and anthropogenic sources. Pyridine was 

detected among the natural volatile components of several foods, including fried chicken, Beaufort 

cheese, sukiyaki, fried bacon, and frozen mango (Dumont and Adda 1978; Ho et al. 1983; MacLeod 

and Snyder 1.988; Shibamoto et al. 1981; Tang et al. 1983). The concentration was reported only for 

mango at 1.0 μg/g (MacLeod and Snyder 1988). Pyridine is approved by the Food and Drug 

administration (FDA) for use as a flavoring agent (Table 7-l) and, therefore, may be present in other 

foods as well. Pyridine has also been identified as a component of tobacco smoke (Curvall et al. 1984; 

Florin et al. 1980; Riebe et al. 1982) and is a coffee aroma constituent (Aeschbacher et al. 1989). 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Humans may be exposed to pyridine by inhalation, ingestion, or dermal contact. However, in 

the United States the general population is most likely to be exposed to pyridine by the ingestion of 

foods naturally containing this compound or, possibly, by inhalation of tobacco smoke. EPA (1978) 

reported that total pyridine is estimated to be ingested in the United States at about 500 mg/year, per 

person, mainly from food. The presence of pyridine in expired air is not necessarily an indicator of 

exposure to this chemical since pyridine has been detected in the expired air (detection limits not 

specified) of nonsmoking subjects described as prediabetic (i.e., nine offspring of diabetic parents and 

five subjects having one diabetic parent and several diabetic relatives) (Krotoszynski and O'Neill 

1982). Pyridine was not detected in the expired air of 20 nonsmoking control (nondiabetic) or 28 

diabetic subjects. 

The greatest potential for exposure to pyridine occurs in the workplace. 

Occupational exposures, usually by inhalation or dermal absorption, may occur during pyridine 

production or its use as a chemical intermediate or solvent (Santodonato et al. 1985). Additional 

exposures may occur at coke-oven and oil-shale processing facilities. Reported workplace TWA 

concentrations range from 0.02 to 3.2 mg/m3

 (ppm) (EPA 1982b), but these data do not include 

cokeoven plants. It has been estimated that maximum long-term workplace exposures 
51 

5. POTENTIAL FOR HUMAN EXPOSURE 

to pyridine will not exceed 3.2-16 mg/m3, except for possible brief exposures to higher concentrations 

(Santodonato et al. 1985). The National Institute for Occupational Health and Safety (NIOSH) 

estimated that the number of workers exposed to pyridine increased from about 29,000 during the early 

1970s (NOHS 1990) to about 41,000 during the early 1980s (NOES 1990). These estimates also do not 

include workers at coke-oven plants. Neither the NOHS nor the NOES databases contain information 

on the frequency, concentration, or duration of exposure of workers to any of the chemicals listed 

therein. These surveys provide only estimates of the number of workers potentially exposed to 

chemicals in the workplace. 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Workers in industrial facilities that manufacture, use, or produce fugitive emissions of pyridine 

have the highest potential for exposure to this compound. Other populations with potentially higher 

than average exposure are those living in the vicinity of these facilities or of hazardous waste sites 

at which pyridine has been identified. 

5.7 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in 

consultation with the Administrator of EPA and agencies and programs of the Public Health Service) 

to assess whether adequate information on the health effects of pyridine is available. Where adequate 

information is not available, ATSDR, in conjunction with the NTP, is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for 

developing methods to determine such health effects) of pyridine. 

The following categories of possible data needs have been identified by a joint team of 

scientists from ATSDR, NTP, and EPA. They are defined as substance-specific informational needs 

that, if met, would reduce or eliminate the uncertainties of human health assessment. In the future, the 

identified data needs will be evaluated and prioritized, and a substance-specific research agenda will be 

proposed. 

5.7.1 Data Needs 

Physical and Chemical Properties. Most of the physical/chemical properties required to 

predict the environmental fate and transport of pyridine have been measured. However, it appears that 

the volatility and sorption of pyridine from water varies considerably with the pH of the water 

(Baker and Luh 1971). Additional data on the effect of pH on the Henry's law constant, volatilization 

rate, and Koc would be useful to predict more accurately the environmental fate of pyridine. 
52
 

5. POTENTIAL FOR HUMAN EXPOSURE 

Production, Import/Export, Use, and Disposal. Information is generally available regarding 

the production, use, and disposal of pyridine in commercial facilities (Harper et al. 1985; HSDB 1989). 

The production locations, major uses, and disposal methods have been identified, and land disposal of 

pyridine is restricted by EPA. However, current production, import, and disposal volumes were not 

located. Releases from manufacturing and use facilities are reported in the TRI, but fugitive emissions 

from cokeoven and oil-shale processing facilities have not been reported. These data would be useful 

in evaluating both occupational exposures and exposures of the populations living in the vicinity of 

these facilities. 

According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. 

Section 11023, industries are required to submit chemical release and off-site transfer information to 

the EPA. The Toxics Release Inventory (TRI), which contains this information for 1987, became 

available in May of 1989. This database will be updated yearly and should provide a list of industrial 

production facilities and emissions. 

Environmental Fate. The available data are insufficient to predict accurately the 

environmental fate of pyridine. Pyridine most likely partitions to soils and sediments and from the 

atmosphere to water vapor. Additional data regarding the Koc of pyridine, especially in nonacidic 

environments, would be useful in confirming the likelihood of pyridine partitioning among 

environmental media. 

Data on transport and degradation are limited. Data on the composition and fate of the products 

of the atmospheric photodegradation of pyridine would enhance our understanding of the atmospheric 

fate of this compound, and additional studies on the biodegradation of pyridine in water and soil would 

be helpful in evaluating the fate of pyridine in these media. 

Bioavailability from Environmental Media. Pyridine is very soluble in water (Sax and Lewis 

1987). Human and animal data indicate that it is well absorbed by the oral route (D'Souza et al. 1980). 

It is expected to be available when it is present in natural waters. Under acidic conditions, it will 

adsorb to soils and sediments to some degree (Baker and Luh 1971). However, ingestion of soil-bound 

pyridine is an unlikely route of exposure. Information on dermal absorption from water would be 

useful in assessing the potential effects of recreational use of natural waters contaminated with 

pyridine. Information on absorption of inhaled pyridine released to the air would also be useful in 

assessing its bioavailability from that medium. 

Food Chain Bioaccumulation. Because of pyridine's low Kow (Verschueren 1983) and high water 

solubility (Sax and Lewis 1987), it probably will not bioconcentrate in plants, aquatic organisms, or 

animals. However, no data on bioconcentration factors or biomagnification in terrestrial or aquatic food 
53
 

5. POTENTIAL FOR HUMAN EXPOSURE
 

chains were located. Additional information on bioconcentration and biomagnification is needed to 

confirm the predicted limited importance of these processes in the environmental fate of pyridine. 

Exposure Levels in Environmental Media. Although pyridine has been identified in air, 

water, and sediments, data regarding pyridine concentrations in environmental media are sparse. The 

available data are insufficient to evaluate the potential for human exposure to this compound; 

therefore, human intake levels of pyridine from environmental media have not been estimated. 

Additional monitoring data for this compound in all media in the vicinity of identified potential 

pollution sources and at hazardous waste sites would be useful in assessing the potential for human 

exposure. In addition, identification and monitoring of those foods to which pyridine is added as a 

flavoring agent would increase the accuracy of estimates of human intake by this route of exposure. 

Exposure Levels in Humans. It would be useful to collect information on levels of exposure 

to pyridine in the environment that are associated with blood, urine, or tissue levels of pyridine and/or 

its metabolites in the exposed populations. Additional information relating those levels to the 

subsequent development of health effects would also be extremely useful. 

Exposure Registries. No exposure registries for pyridine were located. This compound is not 

currently one of the compounds for which a subregistry has been established in the National Exposure 

Registry. The compound will be considered in the future when chemical selection is made for 

subregistries to be established. The information that is amassed in the National Exposure Registry 

facilitates the epidemiological research needed to assess adverse health outcomes that may be related 

to the exposure to this compound. 

5.7.2 On-going Studies 

Remedial investigations and feasibility studies conducted at the 4 NPL humans sites known to 

be contaminated with pyridine will add to the available database on exposure levels in environmental 

media, exposure levels in and exposure registries. 

No other on-going studies were located regarding the environmental transport, or potential for 

human exposure to pyridine. 

55
 

6. ANALYTICAL METHODS
 

The purpose of this chapter is to describe the analytical methods that are available for detecting 

and/or measuring and monitoring pyridine in environmental media and in biological samples. The 

intent is not to provide an exhaustive list of analytical methods that could be used to detect and 

quantify pyridine. Rather, the intention is to identify well-established methods that are used as the 

standard methods of analysis. Many of the analytical methods used to detect pyridine in environmental 

samples are the methods approved by federal agencies such as EPA and the National Institute for 

Occupational Safety and Health (NIOSH). Other methods presented in this chapter are those that are 

approved by groups such as the Association of Official Analytical Chemists (AOAC) and the 

American Public Health Association (APHA). Additionally, analytical methods are included that refine 

previously used methods to obtain lower detection limits, and/or to improve accuracy and 

precision. 

As a volatile to semivolatile material, pyridine can be determined by gas chromatography (GC) 

analysis using mass spectrometric (MS) detection. Pyridine is usually collected from the gas phase on a 

column of solid sorbent, such as Tenax Pyridine can be removed from aqueous or slurry samples by 

purge-and-trap techniques or as headspace gas. Cryogenic (low temperature) collection and sorption in 

organic liquids are also possible. 

6.1 BIOLOGICAL MATERIALS 

In biological systems in which pyridine may have been metabolized or may itself be a 

metabolite, consideration should be given to the possible binding of the analyte by endogenous 

substances in the biological system. However, no information was found in the literature pertaining to 

such binding or to the release of biologically bound pyridine prior to analysis. 

Sensitive and selective methods are available for the qualitative and quantitative measurement 

of pyridine after it is separated from its sample matrix. Gas chromatography, using either sensitive and 

highly specific MS or highly sensitive flame ionization detection (FID), is the analytical method most 

commonly used. Capillary gas chromatography, also known as highresolution gas chromatography 

(HRGC), has facilitated the analysis of compounds such as pyridine that can be measured by gas 

chromatography and has resulted in improvements in resolution and sensitivity. It has made the choice 

of a stationary phase less important than was previously the case with packed columns. The 

instrumental capability to separate volatile analytes by HRGC is, for the most part, no longer the 

limiting factor in their analysis. High-performance liquid chromatography (HPLC) has been used to 

measure isotopically labelled pyridine and its metabolites in urine (Shaker et al. 1982). This method 

has the advantage of compatibility with the liquid matrix of biological samples. 
56 

6. ANALYTICAL METHODS 

In biological samples, after pyridine is released from the sample matrix, it is usually determined 

by gas chromatography. Methods for the detection of pyridine in biological materials are summarized 

in Table 6-l. 

6.2 ENVIRONMENTAL SAMPLES 

For the determination of pyridine in air, the analyte is usually trapped and concentrated from a 

large volume of air on a solid sorbent, such as Tenax or activated carbon, from which it can be 

released thermally or eluted with a solvent such as dichloromethane for subsequent measurement. For 

aqueous samples, pyridine is purged with an inert gas, collected on a solid such as Tenax, or 

cryogenically collected, followed by thermal desorption and measurement. Gas chromatography using 

sensitive and highly specific MS or highly sensitive FID are the analytical methods of choice for the 

determination of pyridine in environmental samples. 

Methods for the determination of pyridine in environmental samples are summarized in Table 

6.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in 

consultation with the Administrator of EPA and agencies and programs of the Public Health Service) 

to assess whether adequate information on the health effects of pyridine is available. Where adequate 

information is not available, ATSDR, in conjunction with the NTP, is required to assure the initiation 

of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of pyridine. 

The following categories of possible data needs have been identified by a joint team of 

scientists from ATSDR, NTP, and EPA. They are defined as substance-specific informational needs 

that, if met, would reduce or eliminate the uncertainties of human health assessment. In the future, the 

identified data needs will be evaluated and prioritized, and a substance-specific research agenda will be 

proposed. 

6.3.1 Data Needs 

Sensitive and selective methods are available for the qualitative and quantitative measurement 

of pyridine after it is separated from its sample matrix. 

An area of continuing interest is the ability to transfer analytes that have been isolated from a 

biological or environmental matrix quantitatively and in a narrow band to the HRGC; therefore this is 

an area of on-going study. 


59 

6. ANALYTICAL METHODS 

Another area of interest is to identify and accurately measure the quantity of compounds in the HRGC 

peaks. Mass spectrometric detection and Fourier transform infrared spectroscopy (FTIR) have been 

useful for this purpose. 

The metabolites of pyridine in biological materials are difficult to determine in routine practice 

because of the lack of standardized methods for their measurement. In addition, not all of the pyridine 

metabolites have been identified and characterized, and this must first be accomplished. 

Methods for Determining Biomarkers of Exposure and Effect. As with most xenobiotics, 

the identification of biomarkers of exposure to pyridine would be helpful in detecting exposure to this 

compound before adverse morphological or clinical effects occur. There is no available information in 

the literature that can be used to correlate levels of exposure to pyridine with resulting levels in urine 

or other biological fluids. Once biomarkers are identified, research on methods to detect them would 

be useful. 

Similarly, no methods have been identified that are sensitive enough to correlate levels in 

biological media with levels at which biological effects occur. The development of these methods 

would be useful in the protection of populations exposed to pyridine. 

Methods for Determining Parent Compounds and Degradation Products in 

Environmental Media. The media of most concern for human exposure to pyridine are drinking water 

(primarily from groundwater sources) and air. As illustrated by the data presented in Table 6-2 (e.g., 

Frei et al. 1974; NIOSH 1984; Sasai and Tsukioka 1981), the methods available for the determination 

of pyridine in water and air are not adequate to determine natural background levels of this compound. 

However, these background levels may well be insignificantly low. Methods are certainly adequate to 

measure the levels of pyridine at which known health effects occur. In general, the precision, accuracy, 

reliability, and specificity of methods to determine pyridine in water and air are not adequately 

documented. Additional work in this area would be useful. 

Methods for determining pyridine in water, air, and waste samples are undergoing constant 

improvement. For example, research is on-going to develop a "Master Analytical Scheme" for the 

determination of organic compounds, including pyridine, in water (Michael et al. 1988). The goal of 

this project is to detect and quantitatively measure organic compounds at 0.1 μg/L in drinking water, 1 

μg/L in surface waters, and 10 μg/L in effluent waters. Analytes are to include numerous nonvolatile 

compounds and some compounds that are only semisoluble in water, as well as volatile compounds (bp 

<150°C). 

Sampling methodologies for compounds such as pyridine continue to pose problems such as 

nonrepresentative samples, insufficient sample volumes, contamination, and the need for labor-intensive, 

tedious extraction and purification procedures (Green and Le Pape 1987). Although HPLC methods have 
60 

6. ANALYTICAL METHODS 

simplified these procedures, it is desirable to have the means to measure organic compounds such as 

pyridine in situ in water and in other environmental media without the need for these sampling and 

extraction procedures to isolate the analyte prior to analysis. 

6.3.2 On-going Studies 

The Environmental Health Laboratory Sciences Division of the Center for Environmental 

Health and Injury Control, Centers for Disease Control, is developing methods for the analysis of 

pyridine and other volatile organic compounds in blood. These methods use high resolution gas 

chromatography and magnetic sector mass spectrometry which gives detection limits in the low 

parts per trillion range. 

The Cooperative Institute for Research in Environmental Sciences (CIRES) at the University of 

Colorado, Boulder, is conducting research to improve methods of analysis for pyridine and related 

compounds in environmental samples. 

Improvements continue to be made in chromatographic separation and detection. Problems 

associated with the collection of pyridine on a sorbent trap, followed by thermal sorption, may be 

overcome with direct purging to a capillary column with whole column cryotrapping (Pankow and 

Rosen 1988) or by trapping on a very thick film (about 100 pm) of cross-linked silicone 

(Roeraade and Blomberg 1989). Current activities in the areas of supercritical fluid extraction (King 

1989) and supercritical fluid chromatography (Smith 1988) include determination of compounds such 

as pyridine in biological samples and environmental media. Fourier transform infrared flow cell 

detectors are sensitive and selective for the detection of compounds such as pyridine that have been 

separated by supercritical fluid chromatography (Wieboldt et al. 1988). Immunoassay methods of 

analysis are also promising for the determination of various organic substances, and it is 

reasonable to assume that pyridine and its metabolites are candidates for this type of analysis. 
61 

7. REGULATIONS AND ADVISORIES 

Because of its potential to cause adverse health effects in exposed people, a number of 

regulations and guidelines have been established for pyridine by various national and state agencies. 

These values are summarized in Table 7-1. 

63
 

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of organic chemicals in fish. Environ Sci Technol 8:113-115. 

*Neff JS. 1886. Pyridine in the treatment of asthma. NY Med J (March 18):299-301. 

*NIOSH. 1984. Pyridine-method 2505. In: NIOSH manual of analytical methods. 3rd ed. Cincinnati, 

OH: National Institute for Occupational Safety and Health. DHHS (NIOSH) Publication No. 84-100. 

*NIOSH. 1985. Pocket guide to chemical hazards. Washington, DC: U.S. Department of Health and 

Human Services, Public Health Service, Centers for Disease Control, National Institute for 

Occupational Safety and Health. 

*NLM . 1989. Chemline. National Library of Medicine, Bethesda, MD. December 15, 1989. 

*NOES. 1990. National Occupational Exposure Survey. National Institute of Occupational Safety and 

Health, Cincinnati, OH. January 3, 1990. 

*NOHS. 1990. National Occupational Hazard Survey. National Institute of Occupational Safety and 

Health, Cincinnati, OH. January 23, 1990. 

*NSC. 1978. Data sheet: Pyridine. Chicago, IL: National Safety Council 
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*OSHA. 1989. U.S. Department of Labor. Occupational Safety and Health Administration: Part III. 

Federal Register 54:2332-2335, 2950. 

Pai V, Bloomfield SF, Jones J, et al. 1978. Mutagenicity testing of nitrogenous compounds and their 

N-oxidized products using TRP+

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nitrogen. Gand Biomedical Press, 375-382. Elsevier/North-Holland Biomedical Press, 375-382. 

*Pankow JF, Rosen ME. 1988. Determination of volatile compounds in water by purging directly to a 

capillary column with whole column cryotrapping. Environ Sci Technol 22:398-405. 

*Pellizzari ED, Castillo NP, Willis S, et al. 1979. Identification of organic components in aqueous 

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water and wastewater. American Society for Testing and Materials. ASTM STP 686, 256-274. 

Perrin DD. 1964. The effect of temperature on pK values of organic bases. Aust J Chem 17:484-488. 

Perrin DD. 1965. Dissociation constants of organic bases in aqueous solution. London, England: 

Butterworths, 178-183. 

*Pinsky C, Bose R. 1988. Pyridine and other coal tar constituents as free radical-generating 

environmental neurotoxicants. Mol Cell Biochem 84:217-222. 

*Pollock LJ, Finkelman I, Arieff AJ. 1943. Toxicity of pyridine in man. Arch Intern Med 71:95-106. 

Proctor NH, Hughes JP, Fischman ML. 1988. Chemical hazards of the workplace. 2nd ed. 

Philadelphia, PA: J.B. Lippincott Company. 

*Reinhardt CF, Brittelli MR. 1981. Patty's industrial hygiene and toxicology. Volume 2A: Toxicology. 

3rd ed. New York, NY: John Wiley and Sons, 2727-2732. 

*Riebe M, Westphal K, Fortnagel P. 1982. Mutagenicity testing, in bacterial test systems, of some 

constituents of tobacco. Mutat Res 101:39-43. 

Rivera RL. 1990. Written communication (March 13) to Barry L. Johnson, Agency for Toxic 

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Department of Environmental Quality, State of Oregon, Portland, OR. 

Roberts PV, Reinhard M, Valocchi AJ. 1982. Movement of organic contaminants in groundwater: 

Implications for water supply. J Am Water Works Assoc 74:408-413. 
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*Roeraade J, Blomberg S. 1989. New methodologies in trace analysis of volatile organic compounds. J 

High Resolut Chromatogr 12:138-141. 

Roubickova J. 1986. [Biological treatment of waste water with higher concentrations of pyridine 

bases.] Vodni Hospod B 36:271-277. (Czech) 

*Roy WR, Griffin RA. 1985. Mobility of organic solvents in water-saturated soil materials. Environ 

Geol Water Sci 7:241-247. 

*Ruffo C, Galli E, Arpino A. 1984. Comparison of methods for the biodegradability evaluation of 

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Hyg Assoc J 47:A-142-A-151. 

*Santodonato J, Bosch S, Meylan W, et al. 1985. Monograph on human exposure to chemicals in the 

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*Sax NI. 1984. Dangerous properties of industrial materials. 6th ed. New York, NY: Van Nostrand 

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pyridine derivatives. Mutat Res 163:23-31. 

 

81
 

9. GLOSSARY
 

Acute Exposure -- Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption Coefficient (Koc) -- The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd) -- The amount of a chemical adsorbed by a sediment or soil (i.e., the solid 

phase) divided by the amount of chemical in the solution phase, which is in equilibrium with the solid 

phase, at a fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per 

gram of soil or sediment. 

Bioconcentration Factor (BCF) -- The quotient of the concentration of a chemical in aquatic 

organisms at a specific time or during a discrete time period of exposure divided by the concentration 

in the surrounding water at the same time or during the same period. 

Cancer Effect Level (CEL) -- The lowest dose of chemical in a study, or group of studies, that 

produces significant increases in the incidence of cancer (or tumors) between the exposed population 

and its appropriate control. 

Carcinogen -- A chemical capable of inducing cancer. 

Ceiling Value -- A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure -- Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Developmental Toxicity -- The occurrence of adverse effects on the developing organism that may 

result from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any 

point in the life span of the organism. 

Embryotoxicity and Fetotoxicity -- Any toxic effect on the conceptus as a result of prenatal exposure 

to a chemical; the distinguishing feature between the two terms is the stage of development during 

which the insult occurred. The terms, as used here, include malformations and variations, altered 

growth, and in utero death. 

EPA Health Advisory -- An estimate of acceptable drinking water levels for a chemical substance 

based on health effects information. A health advisory is not a legally enforceable federal standard, 
 82
 

9. GLOSSARY
 

but serves as technical guidance to assist federal, state, and local officials. 

Immediately Dangerous to Life or Health (IDLH) -- The maximum environmental concentration of 

a contaminant from which one could escape within 30 min without any escape-impairing symptoms or 

irreversible health effects. 

Intermediate Exposure -- Exposure to a chemical for a duration of 15-364 days as specified in the 

Toxicological Profiles. 

Immunologic Toxicity -- The occurrence of adverse effects on the immune system that may result 

from exposure to environmental agents such as chemicals. 

In Vitro -- Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo -- Occurring within the living organism. 

Lethal Concentration(LO) (LC50) -- The lowest concentration of a chemical in air which has been 

reported to have caused death in humans or animals. 

Lethal Concentration (50) (LC50) -- A calculated concentration of a chemical in air to which exposure 

for a specific length of time is expected to cause death in 50% of a defined experimental animal 

population. 

Lethal Dose(LO) (LD50) -- The lowest dose of a chemical introduced by a route other than inhalation 

that is expected to have caused death in humans or animals. 

Lethal Dose(50) (LD50) -- The dose of a chemical which has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50) -- A calculated period of time within which a specific concentration of a 

chemical is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL) -- The lowest dose of chemical in a study or 

group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Malformations -- Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level -- An estimate of daily human exposure to a chemical that is likely to be without 

an appreciable risk of deleterious effects (noncancerous) over a specified duration of exposure. 
83 

9. GLOSSARY 

Mutagen -- A substance that causes mutations. A mutation is a change in the genetic material in a 

body cell. Mutations can lead to birth defects, miscarriages, or cancer. 

Neurotoxicity -- The occurrence of adverse effects on the nervous system following exposure to 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL) -- The dose of chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen 

between the exposed population and its appropriate control. Effects may be produced at this dose, but 

they are not considered to be adverse. 

Octanol-Water Partition Coefficient (Kow) -- The equilibrium ratio of the concentrations of a 

chemical in n-octanol and water, in dilute solution. 

Permissible Exposure Limit (PEL) -- An allowable exposure level in workplace air averaged over an 

8-hour shift. 

q1* -- The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3 for air). 

Reference Dose (RfD) -- An estimate (with uncertainty spanning perhaps an order of magnitude) of 

the daily exposure of the human population to a potential hazard that is likely to be without risk of 

deleterious effects during a lifetime. The RfD is operationally derived from the NOAEL (from 

animal and human studies) by a consistent application of uncertainty factors that reflect various types 

of data used to estimate RfDs and an additional modifying factor, which is based on a professional 

judgment of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects 

such as cancer. 

Reportable Quantity (RQ) -- The quantity of a hazardous substance that is considered reportable 

under CERCLA. Reportable quantities are: (1) 1 lb or greater or (2) for selected substances, an amount 

established by regulation either under CERCLA or under Sect. 311 of the Clean Water Act. Quantities 

are measured over a 24-hour period. 

Reproductive Toxicity -- The occurrence of adverse effects on the reproductive system that may 

result from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the 

related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual 

behavior, fertility, pregnancy outcomes, or modifications in other functions that are Dependent on the 

integrity of this system. 
84
 

9. GLOSSARY
 

Short-Term Exposure Limit (STEL) -- The maximum concentration to which workers can be 

exposed for up to 15 min continually. No more than four excursions are allowed per day, and there 

must be at least 60 min between exposure periods. The daily TLV-TWA may not be exceeded. 

Target Organ Toxicity -- This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single 

limited exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen -- A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV) -- A concentration of a substance to which most workers can be 

exposed without adverse effect. The TLV may be expressed as a TWA, as a STEL, or as a CL. 

Time-weighted Average (TWA) -- An allowable exposure concentration averaged over a normal 8-

hour workday or 40-hour workweek. 

Toxic Dose (TD50) -- A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Uncertainty Factor (UF) -- A factor used in operationally deriving the RfD from experimental data. 

UFs are intended to account for (1) the variation in sensitivity among the members of the human 

population, (2) the uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in 

extrapolating from data obtained in a study that is of less than lifetime exposure, and (4) the 

uncertainty in using LOAEL data rather than NOAEL data. Usually each of these factors is set equal to 

10. 
A-l 

APPENDIX A 

USER'S GUIDE
 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in nontechnical language. Its intended 

audience is the general public especially people living in the vicinity of a hazardous waste site or 

substance release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the substance. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence 

that will direct the reader to chapters in the profile that will provide more information on the given 

topic. 

Chapter 2 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (2-1, 2-2, and 2-3) and figures (2-l and 2-2) are used to summarize health effects by duration of 

exposure and endpoint and to illustrate graphically levels of exposure associated with those effects. All 

entries in these tables and figures represent studies that provide reliable, quantitative estimates of NoObserved-Adverse-Effect Levels (NOAELS), Lowest-Observed- Adverse-Effect Levels (LOAELs) for 

Less Serious and Serious health effects, or Cancer Effect Levels (CELs). In addition, these tables and 

figures illustrate differences in response by species, Minimal Risk Levels (MRLs) to humans for 

noncancer end points, and EPA's estimated range associated with an upper-bound individual lifetime 

cancer risk of 1 in 10,000 to 1 in 10,000,000. The LSE tables and figures can be used for a quick 

review of the health effects and to locate data for a specific exposure scenario. The LSE tables and 

figures should always be used in conjunction with the text. 

The legends presented below demonstrate the application of these tables and figures. A representative 

example of LSE Table 2-l and Figure 2-l are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See LSE Table 2-l 

(1). Route of Exposure One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. When 

sufficient data exist, 
A-2 

APPENDIX A 

three LSE tables and two LSE figures are presented in the document. The three LSE tables 

present data on the three principal routes of exposure, i.e., inhalation, oral, and dermal (LSE 

Table 2-1, 2-2, and 2-3, respectively). LSE figures are limited to the inhalation (LSE Figure 2­

l) and oral (LSE Figure 2-2) routes. 

(2.) Exposure Duration Three exposure periods: acute (14 days or less); intermediate (15 to 364 

days); and chronic (365 days or more) are presented within each route of exposure. In this 

example, an inhalation study of intermediate duration exposure is reported. 

(3.) Health Effect The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the “System” column of the LSE table. 

(4.) Key to Figure Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to define a NOAEL and a Less Serious LOAEL 

(also see the two "18r" data points in Figure 2-l). 

(5.) Species The test species, whether animal or human, are identified in this column. 

(6.) Exposure Frequency/Duration The duration of the study and the weekly and daily exposure 

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to [substance x] via inhalation 

for 13 weeks, 5 days per week, for 6 hours per day. 

(7.) System This column further defines the systemic effects. These systems include: respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not 

covered in these systems. In the example of key number 18, one systemic effect (respiratory) 

was investigated in this study. 

(8.) NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at 

which no harmful effects were seen in the organ system studied. Key number 18 reports a 

NOAEL of 3 ppm for the respiratory system which was used to derive an intermediate 

exposure, inhalation MRL of 0.005 ppm (see footnote “c”). 

(9.) LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest exposure level used 

in the study that caused a harmful health effect. LOAELs have been classified into "Less 

Serious" and "Serious" effects. These distinctions help readers identify the levels of exposure at 

which adverse health effects first appear and the gradation of effects with increasing dose. A 

brief description of the specific end point used to 
A-3 

APPENDIX A 

quantify the adverse effect accompanies the LOAEL. The "Less Serious" respiratory effect 

reported in key number 18 (hyperplasia) occurred at a LOAEL of 10 ppm. 

(10). Reference The complete reference citation is given in Chapter 8 of the profile. 

(11). CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of 

carcinogenesis in experimental or epidemiological studies. CELs are always considered serious 

effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report 

doses which did not cause a measurable increase in cancer. 

(12). Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote "c" indicates the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See LSE Figure 2-1 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure levels for particular exposure duration. 

(13). Exposure Duration The same exposure periods appear as in the LSE table. In this example, 

health effects observed within the intermediate and chronic exposure periods are illustrated. 

(14).	 Health Effect These are the categories of health effects for which reliable quantitative data 

exist. The same health effects appear in the LSE table. 

(15).	 Levels Of Exposure Exposure levels for each health effect in the LSE tables are graphically 

displayed in the LSE figures. Exposure levels are reported on the log scale "y" axis. Inhalation 

exposure is reported in mg/m3

 or ppm and oral exposure is reported in mg/kg/day. 

(16).	 NOAEL In this example, 18r NOAEL is the critical end point for which an intermediate 

inhalation exposure MRL is based. As you can see from the LSE figure key, the open-circle 

symbol indicates a NOAEL for the test species (rat). The key number 18 corresponds to the 

entry in the LSE table. The dashed descending arrow indicates the extrapolation from the 

exposure level of 3 ppm (see entry 18 in the Table) to the MRL of 0.005 ppm (see footnote "b" 

in the LSE table). 

(17).	 CEL Key number 38r is one of three studies for which Cancer Effect Levels (CELs) were 

derived. The diamond symbol refers to a CEL for the test species (rat). The number 38 

corresponds to the entry in the LSE table. 
A-4 

APPENDIX A 

(18). Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the 

upper-bound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from EPA's Human Health Assessment Group's upper-bound estimates of the slope of the cancer 

dose response curve at low dose levels (q1*). 

(19). Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. 


A-7
 

APPENDIX A
 

Chapter 2 (Section 2.4) 

Relevance to Public Health 

The Relevance to Public Health section provides a health effects summary based on evaluations of 

existing toxicological, epidemiological, and toxicokinetic information. This summary is designed to 

present interpretive, weight-of-evidence discussions for human health end points by addressing the 

following questions. 

1.What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The section discusses health effects by end point. Human data are presented first, then animal data. 

Both are organized by route of exposure (inhalation, oral, and dermal) and by duration (acute, 

intermediate, and chronic). In vitro data and data from parenteral routes (intramuscular, intravenous, 

subcutaneous, etc.) are also considered in this section. If data are located in the scientific literature, a 

table of genotoxicity information is included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, andcardinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. MRLs for noncancer end points if derived, and the end 

points from which they were derived are indicated and discussed in the appropriate section(s). 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to 

public health are identified in the Identification of Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information was available, MRLs were derived. MRLs are specific for 

route (inhalation or oral) and duration (acute, intermediate, or chronic) of exposure. Ideally, MRLs can 

be derived from all six exposure scenarios (e.g., Inhalation - acute, -intermediate, -chronic; Oral -

acute, - intermediate, - chronic). These MRLs are not meant to support regulatory action, but to aquaint 

health professionals with exposure levels at which adverse health effects are not expected to occur in 

humans. They should help physicians and public health officials determine the safety of a community 

living near a substance emission, given the concentration of a contaminant in air or the estimated daily 

dose received via food or water. MRLs are based largely on toxicological studies in animals and on 

reports of human occupational exposure. 
A-8 

APPENDIX A 

MRL users should be familiar with the toxicological information on which the number is based. 

Section 2.4, "Relevance to Public Health," contains basic information known about the substance. 

Other sections such as 2.6, "Interactions with Other Chemicals" and 2.7, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology used by the Environmental Protection Agency 

(EPA) (Barnes and Dourson, 1988; EPA 1989a) to derive reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the end point which, in its best judgement, represents the 

most sensitive humanhealth effect for a given exposure route and duration. ATSDR cannot make this 

judgement or derive an MRL unless information (quantitative or qualitative) is available for all 

potential effects (e.g., systemic, neurological, and developmental). In order to compare NOAELs 

and LOAELs for specific end points, all inhalation exposure levels are adjusted for 24hr exposures and 

all intermittent exposures for inhalation and oral routes of intermediate and chronic duration are 

adjusted for continous exposure (i.e., 7 days/week). If the information and reliable quantitative data on 

the chosen end point are available, ATSDR derives an MRL using the most sensitive species (when 

information from multiple species is available) with the highest NOAEL that does not exceed any 

adverse effect levels. The NOAEL is the most suitable end point for deriving an MRL. When a 

NOAEL is not available, a Less Serious LOAEL can be used to derive an MRL, and an uncertainty 

factor (UF) of 10 is employed. MRLs are not derived from Serious LOAELs. Additional uncertainty 

factors of 10 each are used for human variability to protect sensitive subpopulations (people 

who are most susceptible to the health effects caused by the substance) and for interspecies variability 

(extrapolation from animals to humans). In deriving an MRL, these individual uncertainty factors are 

multiplied together. The product is then divided into the adjusted inhalation concentration or oral 

dosage selected from the study. Uncertainty factors used in developing a substance-specific MRL are 

provided in the footnotes of the LSE Tables. 



C-l 

APPENDIX C 

PEER REVIEW 

A peer review panel was assembled for pyridine. The panel consisted of the following 

members: Dr. Edmond LaVoie, Professor, Medicinal Chemistry, Rutgers University; Dr. James 

Withey, Research Scientist, Health and Welfare, Canada; Dr. Joseph Sincheiner, Professor, 

Toxicology, University of Michigan. These experts collectively have knowledge of pyridine's physical 

and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and 

animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with 

the conditions for peer review specified in Section 104(i)(13) of the Comprehensive Environment 

Response, Compensation, and Liability Act, as amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have 

reviewed the peer reviewers' comments and determined which comments will be included in the 

profile. A listing of the peer reviewers' comments not incorporated in the profile, with a brief 

explanation of the rationale for their exclusion, exists as part of the administrative record for 

this compound. A list of databases reviewed and a list of unpublished documents cited are also 

included in the administrative record. 

The citation of the peer review panel should not be understood to imply its approval of the 

profile's final content. The responsibility for the content of this profile lies with the ATSDR.