U.S. EPA

High Production Volume Chemical Challenge Program

Robust Summaries and Test Plan

for 2,3-pyridinedicarboxylic acid 

(CAS No. 89-00-9)

Revised Submission

Submitted by:

Exponent, Inc. 

1800 Diagonal Road, Suite 500

Alexandria, VA 22314

On behalf of:

BASF Corporation

3150 Highway JJ

Palmyra, MO 63641

Date of submission:

February 9, 2011
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

ii

Table of Contents

1.0 Executive Summary 1

2.0 Introduction 4

2.1 Overview 4

2.2 Methods for Data Review 4

3.0 Substance Information for 2,3-Pyridinedicarboxylic Acid 6

3.1 Substance Description 6

3.2 Use and Exposure Information 6

4.0 Analog for 2,3-Pyridinedicarboxylic Acid 8

4.1 EPA Guidance for Use of Analogs 8

4.2 Structural Similarity and Comparison of Data for PDC and EPDC 9

5.0 Data Analysis 11

5.1 Physico-chemical Properties 11

5.2 Environmental Fate and Pathways 11

5.3 Ecotoxicity 14

5.4 Health Effects 16

6.0 Conclusions and Recommendations 22

7.0 SIDS Data Matrix 23

8.0 References 25

List of Figures

Figure 1. Structure of 2,3-pyridinedicarboxylic acid 6

Figure 2. Comparison of structures of PDC and EPDC 9
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

iii

List of Tables

Table 1: Testing plan and rationale 3

Table 2. Comparison of physico-chemical properties of PDC and EPDC 10

Table 3. Environmental fate and pathways information for PDC and EPDC 14

Table 4. Ecotoxicity information for PDC and EPDC 16

Table 5. Health effects information for PDC and EPDC 21
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

1

1.0 Executive Summary

2,3-pyridinedicarboxylic acid (CAS No. 89-00-9), also known as PDC or quinolinic acid, is 

solid, with a molecular weight of 167.12 g/mole. The available data for PDC (measured, 

estimated, and from references) were supplemented with data on a related chemical, 2,3-

pyridinedicarboxylic acid, 5-ethyl (CAS No. 102268-15-5), also known as EPDC, which was 

used as an analog. 

2,3-Pyridinedicarboxylic acid is an intermediate in the manufacturing process for the herbicide 

imazapyr. Potential exposures are thought to be extremely limited, because personal protective 

equipment is used during process sampling events when any exposure might occur. 

Environmental exposures are expected to be extremely rare, because any spills would be handled 

in an appropriate manner to minimize release to the environment (which would already be 

limited by the physicochemical properties of PDC). 

EQC Level III fugacity modeling predicts that, if released to the environment, PDC is expected 

to partition primarily to soil (77.0%) and water (22.0%). Vapor-phase PDC, which is expected 

to be limited due to its low volatility, will be degraded in the atmosphere by reaction with 

hydroxyl radicals, with a half-life of 9.9 days. PDC does contain chromophores that absorb at 

wavelengths > 290 nm and therefore may be susceptible to direct photolysis by sunlight. The 

pKa values of 2.43 and 5.48 indicate that PDC will exist almost entirely in ionic form in the 

neutral range of pH and this, coupled with a low vapor pressure and high water solubility, 

indicates that volatilization from water is not expected to be an important fate process. PDC is 

not expected to undergo hydrolysis in the environment due to the lack of functional groups that 

hydrolyze under environmental conditions. Because of its low octanol-water partition 

coefficient, PDC is not expected to bioaccumulate. PDC was found to be readily biodegradable 

in a test conducted according to OECD Guideline 301B. Biodegradation has also been observed 

in soil (100% after 8 days) and in aqueous nutrient solutions inoculated with soil (81% in 5 

days). 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

2

Based upon the available data for EPDC and the use of PDC as an intermediate in the production 

of herbicides, aquatic plants are likely the most sensitive of the three trophic levels used to 

evaluate ecotoxicity. The toxicity of PDC to aquatic plants was therefore determined in a study 

conducted with the green alga, Pseudokirchneriella subcapitata, according to OECD Guideline 

201. The resulting 72-hour EC50 for PDC was >100 mg/L. There are no studies available on the 

toxicity of PDC to fish or invertebrates. However, based upon structure-activity relationships, 

PDC is expected to be non-toxic to aquatic animals (LC50/EC50 well in excess of > 100 mg/L), 

which is supported by the available data for EPDC (EC50 > 100 mg/L for Daphnia magna). 

There are no reliable data on the acute toxicity of PDC to mammals. The acute mammalian 

toxicity of EPDC is low based upon the measured oral LD50 for rats (> 5000 mg/kg bw in one 

study and 4251 mg/kg bw in another study) and the dermal LD50 for rabbits (> 2000 mg/kg bw). 

In a micronucleus test with PDC conducted according to OECD Guideline 474, no clastogenic 

effects or aneugenic activity were seen in bone marrow cells in vivo. Results for EPDC were 

negative (i.e., no response) in the bacterial reverse mutation assay. A combined repeated-dose 

toxicity study with the reproduction/developmental toxicity screen (OECD 422) was performed 

with PDC. The NOAEL for general systemic toxicity was 50 mg/kg bw/day for male rats, based 

upon impaired body weight and pathological findings in the gastrointestinal tract, and 250 mg/kg 

bw/day for female rats based upon pathological findings in the gastrointestinal tract. No effects 

upon reproductive performance or fertility were observed, resulting in a NOAEL for 

reproductive toxicity of 1000 mg/kg bw/day. Similarly, there were no effects on the offspring, 

resulting in a developmental NOAEL of 1000 mg/kg bw/day. 

The original test plan submitted for PDC in February, 2008 identified several data gaps for HPV 

elements. This revised test plan incorporates the results of testing conducted since that date by 

the sponsor to determine the melting point, water solubility, biodegradability, acute toxicity to 

algae, clastogenicity, repeated dose toxicity, reproductive toxicity, and developmental toxicity. 

Including these new data, the overall conclusions and recommendations are that adequate 

information exists for all HPV elements for 2,3-pyridinedicarboxylic acid. This information is 

summarized in Table 1. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

3

Table 1: Testing plan and rationale

CAS #89-00-9

PDC

Information 

Available?

OECD Study?

GLP Study?

Supporting 

Information?

Estimation 

Method?

Acceptable?

Testing 

Recommended?

HPV Endpoint

Physico-chemical Properties

Melting Point Y Y Y Y N Y N

Boiling Point Y N N Y Y Y N

Vapor Pressure Y N N Y Y Y N

Partition Coefficient Y N N Y Y Y N

Water Solubility Y Y Y Y Y Y N

Environmental Fate

Photo-Degradation Y N N Y Y Y N

Water Stability Y N N Y Y Y N

Fugacity Y N N Y Y Y N

Biodegradation Y Y Y Y Y Y N

Ecotoxicity

96-Hour Fish Y N N Y N Y N

48-Hour Invertebrate Y Y Y Y N Y N

96-Hour Algae Y Y Y Y N Y N

Health Effects

Acute Y N N Y N Y N

Genetic Toxicology in vitro Y N N Y N Y N

Genetic Toxicology in vivo Y Y Y Y N Y N

Repeated Dose Y Y Y N N Y N

Reproductive Y Y Y N N Y N

Developmental Y Y Y N N Y N
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

4

2.0 Introduction

2.1 Overview

Exponent, on behalf of BASF Corporation, has prepared the revised robust summaries and 

revised test plan for 2,3-pyridinedicarboxylic acid, also referred to as PDC or quinolinic acid 

(CAS No. 89-00-9), under the United States Environmental Protection Agency’s (U.S. EPA) 

Extended High Production Volume (eHPV) Chemical Challenge Program. 

The purpose of this plan is to develop physicochemical data, environmental fate and effects data, 

and mammalian health effects data for 2,3-pyridinedicarboxylic acid consistent with the 

Screening Information Data Set (SIDS). Therefore, this plan summarizes the existing SIDS data 

for 2,3-pyridinedicarboxylic acid and evaluates the need for testing to fill any data gaps in the 

SIDS endpoints.

2.2 Methods for Data Review

A review of the scientific literature and BASF Corporation’s company data was conducted on the 

physicochemical properties, environmental fate and effects, and mammalian toxicity endpoints 

for 2,3-pyridinedicarboxylic acid and the surrogate, 2,3-pyridinedicarboxylic acid, 5-ethyl-. 

Searches were conducted on CAS numbers and chemical names using the following databases 

and web sites: ATSDR, CICAD, ESIS, HPVIS, HERA, IARC, IPCS INTOX Databank, IRIS, 

Japanese Chemicals Evaluation and Research Institute, NTP, OECD, EFDB, ECOTOX, and 

TOXNET (including TOXLINE, MEDLINE, CCRIS, HSDB, DART, GENETOX, and 

CHEMIDPlus). In addition to these databases and web sites, a literature search was performed 

and standard handbooks (e.g., CRC Handbook on Chemicals, Hawley’s Condensed Chemical 

Dictionary, Merck Index, etc.) were consulted for physicochemical properties. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

5

This document addresses a single HPV sponsored chemical; however, data for a closely related 

compound, 2,3-pyridinedicarboxylic acid, 5-ethyl- (CAS No. 102268-15-5) have been used to 

support the data set for the sponsored chemical through a read-across approach. Data readacross means that physicochemical property and toxicological data from one chemical are used 

to estimate those same characteristics for another chemical, and is appropriate only when the two 

chemicals are deemed sufficiently similar in structure that they are likely to have similar 

chemical and toxicological properties. Typically, the more data-based information there is to 

support this assumption, the stronger the foundation for the read-across approach will be. The 

use of structural analogs is consistent with EPA guidance for use of structure-activity 

relationships (SAR) in the HPV Chemical Challenge Program (EPA, 1999a).

In accordance with U.S. EPA guidance, in those instances where measured physicochemical 

parameters and environmental fate data were not available, these properties were developed 

using EPIWIN (EPISuite version4.0) modeling. EPIWIN is an acronym for the Estimation 

Programs Interface for Microsoft Windows, and is a package of computer programs developed 

by the U.S. EPA Office of Pollution Prevention and Toxics (OPPTS), which uses computational 

methods and structure-activity relationships (SAR) in estimating chemical properties, 

environmental fate, and aquatic toxicity of organic chemicals. Because of the inherent 

limitations of SAR approaches, EPIWIN modeling may produce non-realistic estimates; 

therefore, EPIWIN data are evaluated for reasonableness prior to use. In accordance with EPA 

guidance, environmental transport and fate estimates were developed using the Level III 

Equilibrium Criteria Model (EQC) in EPIWIN v4.0 as described by Mackay et al. (1996). 

Robust summaries were prepared for 2,3-pyridinedicarboxylic acid and 2,3-pyridinedicarboxylic 

acid, 5-ethyl-, in EPA’s High Production Volume Information System (HPVIS) for key studies 

to provide a detailed summary of the test methods and results. Though several studies may have 

been evaluated for a particular SIDS endpoint, in general robust summaries were prepared only 

for the critical study that represented the best available data. Selection of the critical study was 

based on a review of all studies using the ranking system developed by Klimisch et al. (1997), as 

well as the criteria outlined in the U.S. EPA’s (1999b) methods for determining the adequacy of 

existing data. Reliable studies that provided supporting data were also included. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

6

3.0 Substance Information for 2,3-Pyridinedicarboxylic 

Acid

3.1 Substance Description

2,3-pyridinedicarboxylic acid (CAS No. 89-00-9), also known as pyridine-2,3-dicarboxylic acid 

or PDC, is used by BASF to manufacture the herbicide imazapyr. Other uses are as an 

intermediate in the production of nicotinic acid (HSDB, 2007). It is an odorless solid with a 

molecular weight of 167.12 g/mole. Also known as quinolinic acid, this compound can also be 

produced as an endogenous metabolite of L-tryptophan via the kynurenine pathway in the 

mammalian central nervous system (HSDB, 2007). 

Figure 1. Structure of 2,3-pyridinedicarboxylic acid

3.2 Use and Exposure Information

PDC is used in the manufacture of the herbicide imazapyr. The production volume of PDC is 

greater than 1 million pounds per year; hence PDC is an HPV chemical. The greatest possibility 

for exposure to workers in the manufacturing process of PDC occurs during the solid charging 

operation. In order to minimize exposure, operators involved in this manufacturing step wear a 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

7

full face organic vapor respirator that includes a dust cartridge, as well as dermal protection. All 

subsequent processing occurs in closed systems with no routine exposure possible except for QC 

sampling. All sampling is performed with the proper personal protective equipment (PPE), using 

sample stations designed to minimize the possibility of exposure. Samples are handled in 

laboratory settings according to a chemical hygiene plan and using engineering controls such as 

fume hoods. PDC is not volatile, so the probability of inhalation exposure is quite low and air 

monitoring is not warranted. Dermal exposures that might be associated with sampling the 

materials (and waste streams) during the manufacturing process are prevented through worker 

training regarding proper health and safety procedures, the use of proper PPE, and engineering 

controls.

The vast majority of PDC is converted to the herbicide imazapyr, and the inventory of PDC on 

site for manufacturing at any one time is small. Larger amounts are stored in warehouses. Any 

small amount of PDC that might end up in the final product is regulated by the active ingredient 

registration. All organic and aqueous waste streams from the process that use PDC are 

incinerated on site or disposed of via an on-site deep well. Potential environmental exposures 

are limited to transportation accidents en route to the manufacturing sites or spills on such sites, 

which are handled in accordance with recognized emergency response and safety procedures, 

respectively, to minimize potential exposures. Should a spill occur, the dispersion of PDC would 

be minimal. As PDC is a solid, a rainfall event would be needed to mobilize the material such 

that it would dissolve into water or bind to soil. The use of secondary containment at the 

manufacturing sites further limits potential environmental release. In summary, PDC poses a 

minimal exposure threat to workers and the environment. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

8

4.0 Analog for 2,3-Pyridinedicarboxylic Acid

4.1 EPA Guidance for Use of Analogs

In its SAR guidance for the HPV Chemical Challenge Program, the EPA states that the most 

likely analogs for an HPV chemical are those that resemble the candidate chemical in terms of 

the following:

1. molecule structure/size; 

2. some substructure that may play a critical functional role;

3. some molecular property (e.g., lipophilicity, electronic and steric parameters); and/or 

4. some precursor, metabolite, or breakdown product.

In general, valid analogs should have close structural similarity and the same functional groups 

as the HPV chemical. In addition, a high correlation is desired between the HPV chemical and 

the putative analog for the following parameters:

 Physicochemical properties (e.g., physical state, molecular weight, log Kow, water 

solubility);

 Absorption potential;

 Mechanism of action of biological activity; and

 Metabolic pathways/kinetics of metabolism.
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

9

4.2 Structural Similarity and Comparison of Data for PDC and 

EPDC

The selected analog for PDC is 2,3-pyridinedicarboxylic acid, 5-ethyl-. Also known as 5-

ethylpyridine-2,3-dicarboxylic acid, or EPDC, this compound differs from the HPV chemical by 

only the addition of an ethyl group, and thus is believed to possess most of the desired properties 

for an analog as described in EPA guidance. The structures of the two chemicals are shown in 

Figure 2.

2,3-pyridinedicarboxylic acid 2,3-pyridinedicarboxylic acid, 5-ethylFigure 2. Comparison of structures of PDC and EPDC

Table 2 compares the properties of PDC and EPDC. The source of the information is classified 

as “measured”, “reference”, or “estimated.” Measured data were obtained through experimental 

procedures, while estimated data were obtained through structure-activity correlations 

(EPIWIN). The designation of reference means that the values were obtained from handbooks 

(such as the Merck Index), from material safety data sheets, or from other sources such as 

databases. Complete details on the sources of information for each data element are provided in 

the Robust Summaries submitted with this Test Plan. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

10

Table 2. Comparison of physico-chemical properties of PDC and EPDC

Substance 

Information and 

Properties

2,3-pyridinedicarboxylic acid

(89-00-9)

2,3-pyridinedicarboxylic acid, 5-ethyl-

(102268-15-5)

Synonym

pyridine-2,3-dicarboxylic acid; PDC; 

quinolinic acid

5-ethylpyridine-2,3-dicarboxylic acid; EPDC

Molecular Formula C7H5NO4 C9H9NO4

Molecular weight 167.12 195.18

Melting point 185 – 190oC (measured)1

157 °C (estimated)

Boiling point 357 °C (estimated) 380 °C (estimated)

Vapor pressure 2.6 x 10-6hPa (estimated) 1.5 x 10-6hPa (estimated)

Water solubility 9.56 g/L (measured)27.5 g/L (estimated)

Partition coefficient 

(log Kow)

-0.12 (estimated) 0.92 (estimated)

Note: estimated values are from EPIWIN

1 Drew, 2008a

2 Drew, 2008b

These compounds have very similar physico-chemical properties and would be expected to have 

very similar environmental fate patterns. The absorption, distribution, metabolism, and 

elimination of these compounds are also expected to be similar. The additional ethyl group on 

EPDC is not expected to have any effect upon either aquatic or mammalian toxicity, and thus the 

available toxicity data for EPDC should have a high predictability for PDC. Therefore, data 

read-across is used for those instances where valid and reliable data are available for EPDC but 

not PDC. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

11

5.0 Data Analysis

A summary of the available data for PDC and EPDC is shown, along with information on the 

reliability of the data, in the completed SIDS data matrix provided in Section 7. These data are 

discussed below, while details are provided in the Robust Summaries submitted concurrently 

with this Test Plan. 

5.1 Physico-chemical Properties

BASF conducted testing to determine the melting point and water solubility of PDC. Melting 

point is a key property that is used in estimation of other properties, while water solubility is a 

key property because of its potential relevance for human and environmental risk assessment. In 

a study conducted according to OECD Guideline 102, the melting point of PDC was determined 

to be 185 – 190 °C (Drew, 2008a). The water solubility was determined to be 9.56 g/L at 22°C in 

a study conducted according to OECD Guideline 105 (Drew, 2008b). The remaining data values 

for physico-chemical properties for PDC and EPDC were obtained from literature references, 

Material Safety Data Sheets (MSDS), and estimation using EPIWIN. These data are presented in 

Table 2 (in the previous section) and in the Robust Summaries. 

Recommendation: No additional physico-chemical properties studies are necessary. The 

available data fill the HPV required data elements with sufficient precision to define the potential 

hazards of PDC.

5.2 Environmental Fate and Pathways

The environmental fate data for 2,3-pyridinedicarboxylic acid and 2,3-pyridinedicarboxylic acid, 

5-ethyl, are summarized in Table 3, below, along with identification of the sources of 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

12

information (reference, measured, or estimated). Additional information is tabulated in Section 7 

and more fully described in the Robust Summaries.

5.2.1 Photodegradation, Volatilization, and Hydrolysis

Indirect photodegradation in air was calculated for PDC and EPDC using AOPWIN v1.92. The 

resulting half-life was approximately 10 days for PDC and 5 days for EPDC. PDC does contain 

chromophores that absorb at wavelengths > 290 nm and therefore may be susceptible to direct 

photolysis by sunlight (HSDB, 2007). The pKa values of 2.43 and 5.48 indicate that PDC will 

exist almost entirely in ionic form at pH values from 5 to 9, and therefore volatilization from 

water is not expected to be an important fate process. In addition, the predicted Henry’s Law 

Constant for PDC is 4.46 x 10-11 atm-m

3

/mole (HENRYWIN v3.20), which is extremely low and 

indicates a lack of volatility. Volatilization from soil was minimal in a study by Sims and 

Sommers (1985). Neither PDC nor EPDC is expected to undergo hydrolysis in the environment 

because of the lack of functional groups that hydrolyze under environmental conditions. 

5.2.2 Bioaccumulation, Fugacity, and Biodegradation

Neither PDC nor EPDC is expected to bioaccumulate, as their log Kow values are calculated to 

be less than 1. If released to the environment, PDC is expected to partition primarily to soil 

(77%) and water (23%), as predicted by EQC Level III fugacity modeling. The behavior of 

EPDC is predicted to be quite similar (84% soil, 16% water). 

A study to determine the biodegradability of PDC in the carbon dioxide evolution test (OECD 

Guideline 301B) was performed, following Good Laboratory Practices (GLP) by Schwarz 

(2009). The test substance, mixed with a defined inorganic medium and a non pre-adapted 

inoculum of activated sludge, was incubated under aerobic conditions for up to 28 days. The 

resulting mean (2 assays) production of carbon dioxide was 80-90% relative to the theoretical 

carbon dioxide after 10 days, indicating that PDC was readily biodegradable under the conditions 

of the test. Studies are also available from the literature in which PDC was demonstrated to 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

13

biodegrade. Sims and Sommers (1985) investigated the fate of 25 pyridine derivatives in soil, 

and concluded that pyridinecarboxylic acids were the most labile. Only 3.8% of 2,3-

pyridinedicarboxylic acid remained after 2 days of incubation, and none was detected after 

8 days. In aqueous nutrient solutions inoculated with soil, Sims and Sommers (1986) observed 

81% biodegradation of PDC within 5 days (based upon the release of inorganic nitrogen) while 

Naik et al. (1972) observed complete aerobic decomposition within 4–8 days and anaerobic 

decomposition within 16–32 days when tested in enriched cultures containing garden soil. 

The ready biodegradability of EPDC was determined according to OECD Guideline 301A, DOC 

Die-Away Test performed under GLP by Schwarz (2007). The test substance, mixed with 

inorganic medium and a non-adapted inoculum (municipal activated sludge) demonstrated less 

than 10% biodegradation after 28 days, as measured by dissolved organic carbon. This result 

indicates that EPDC was not readily biodegradable under the conditions of the test. 

Recommendation: No additional studies on environmental fate and pathways are necessary. 

The HPV required endpoints are fulfilled by a combination of test results and estimation using 

acceptable methods. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

14

Table 3. Environmental fate and pathways information for PDC and EPDC

Environmental Fate 

Endpoint

2,3-pyridinedicarboxylic acid

(89-00-9)

2,3-pyridinedicarboxylic acid, 5-ethyl-

(102268-15-5)

Photodegradation half-life 9.9 days (estimated)14.8 days (estimated)1

Hydrolysis Expected to be stable to hydrolysis Expected to be stable to hydrolysis

Fugacity (percent distribution 

over time assuming equal 

emissions to air, water and 

soil)

Air: <1%; Water: 22.9%; Soil: 77.0%; 

Sediment: <1% (estimated)2

Air: <1%; Water: 16.3%; Soil: 83.6%; 

Sediment: <1% (estimated)2

Biodegradation

Readily biodegradable per OECD 301B.

(Guideline study, reliable without 

restriction)3

Not readily degradable per OECD 301A. 

(Guideline study, reliable without 

restriction)4

1 estimated by AOPWIN v1.92

2

estimated by EQC Level III

3 Schwarz, 2009

4

Schwarz 2007

5.3 Ecotoxicity

The acute toxicity data are summarized in Table 4 and Section 7 and are fully described in the 

Robust Summaries. Because PDC is an intermediate in the production of an herbicide 

(imazapyr), it would be expected that algae would be the most sensitive aquatic organisms 

relative to fish and invertebrates. Therefore, an algal toxicity test was conducted according to 

OECD Guideline 201 and under GLP (Hoffman, 2009). In this study, the green alga 

Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum) was exposed 

for 72 hours to five concentrations of PDC (10 to 100 mg/L in algal medium), which were 

analytically verified to be within an average of 99.7% of nominal at test initiation and 102.5% of 

nominal at test termination. The EC50 was calculated based upon both growth rate (increase in 

biomass per day) and yield (final biomass minus initial biomass) and was >100 mg/L for either 

parameter, indicating that PDC is practically non-toxic to algae1

.

 

1 Ecotoxicity categories are according to http://www.epa.gov/oppefed1/ecorisk_ders/toera_analysis_eco.htm
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

15

The toxicity of EPDC to two aquatic plant species was determined through studies conducted 

under GLP according to current guidelines. Analytical verification of the test concentrations was 

performed. The results of these tests indicate that EPDC is slightly toxic to the green alga, 

Selenastrum capricornutum (96-hour EC50 = 10.8 mg/L; Olivieri, 2000a) and practically nontoxic to the aquatic vascular plant Lemna gibba (14-day EC50 > 101 mg/L; Olivieri, 2000b). In 

comparison to the EC50 for green algae for PDC, it is noted that the former EC50 is from a 

72-hour exposure while the value for EPDC is from a 96-hour exposure and would be expected 

to be lower. 

No test results are available for fish or daphnids for PDC; however predictions made using 

ECOSAR v1.00 indicate that PDC is practically non-toxic to fish and daphnids, with estimated 

LC50/EC50 values of 920 mg/L and 3562 mg/L. A reliable acute toxicity test was conducted 

with EPDC using Daphnia magna (Mulligan, 2000) according to current guidelines, with 

analytical verification of the concentrations of test substance, and under GLP. The results 

indicate that EPDC is practically non-toxic to D. magna (48-hour EC50 > 100 mg/L). ECOSAR 

predicts that EPDC is not toxic to fish with an estimated LC50 of 220 mg/L. 

Recommendation: No additional ecotoxicity studies are necessary. The required HPV 

endpoints are fulfilled via a combination of test data, estimation, and read-across from the 

endpoint information for EPDC. As indicated in Table 4, PDC has similar or less toxicity than 

the analog, EPDC. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

16

Table 4. Ecotoxicity information for PDC and EPDC

Ecotoxicity Endpoint1

2,3-pyridinedicarboxylic acid

(89-00-9)

2,3-pyridinedicarboxylic acid, 5-ethyl-

(102268-15-5)

Acute fish LC50, 96-hour

(mg/L)

920 (estimated)1220 (estimated)1

Acute invertebrate EC50, 

48-hour (mg/L)

3562 (estimated)1

> 100 for Daphnia magna (measured)3

(Guideline study, reliable without restriction) 

Algal inhibition EC50, 

72-hour (mg/L)

> 100 for Pseudokirchneriella 

subcapitata (measured)2

(Guideline study, reliable without 

restriction)

10.8 for Selenastrum capricornutum (96-hour

exposure) (measured)4

(Guideline study, reliable without restriction) 

Aquatic vascular plant 

inhibition EC50, 14-day 

(mg/L)

No data; however, not a SIDS endpoint

> 101 for Lemna gibba (measured)5

(Guideline study, reliable without restriction)

1

estimated by ECOSAR

2 Hoffman, 2009

3 Mulligan, 2000

4 Olivieri, 2000a

5 Olivieri , 2000b

5.4 Health Effects

5.4.1 Absorption, Distribution, Metabolism and Excretion

PDC (quinolinic acid) can be produced as an endogenous metabolite of the amino acid Ltryptophan via the kynurenine pathway in the mammalian central nervous system. This pathway 

of tryptophan metabolism produces L-kynurenine, which can change to the neuroprotective agent 

kynurenic acid or the neurotoxic agent quinolinic acid. Quinolinic acid can act as a brain 

excitotoxin when produced and released by activated macrophages and microglia. A high ratio of 

quinolinic acid/kynurenic acid has been implicated in a variety of inflammatory neurological 

diseases in which excitotoxic cell death is found, e.g., AIDS-related dementia, Huntingdon’s 

disease, and Alzheimer’s disease (HSDB, 2007). 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

17

5.4.2 Acute Toxicity

The only acute toxicity data available for PDC are from a Material Safety Data Sheet (MSDS, 

Science Lab.com), which indicates a rat oral LD50 > 500 mg/kg and a rabbit dermal LD50 > 

200 mg/kg. Results of studies conducted according to acceptable guidelines and under GLP are 

available for EPDC, however. These data indicate that EPDC is practically non-toxic. In a limit 

test, the rat oral LD50 value was >5000 mg/kg bw for both males and females (Lowe, 1999). In a 

study using four doses from 1250 to 7500 mg/kg bw, the oral LD50 for the rat was determined to 

be 4251 mg/kg bw for both sexes combined (Fischer, 1985). Because the study by Fischer 

(1985) used four doses and identified the LD50, this is considered the key study for acute 

toxicity. A limit test conducted with rabbits determined the dermal LD50 to be 2000 mg/kg bw

(Fischer, 1985). These data are presented in Table 5.

5.4.3 Repeated dose toxicity

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening 

test (OECD Guideline 422) was conducted with PDC, under GLP (Buesen et al., 2010). Parental 

(F0) male and female Wistar rats (10 per sex per dose) were exposed to 50, 250, and 1000 mg/kg 

bw-day of the test substance via daily oral gavage. The vehicle control was 1% carboxymethylcellulose. The duration of treatment was 31–56 days, covering a 2-week pre-mating and 

mating period in both sexes, approximately 1 week post-mating in males, and the entire gestation 

period as well as 4 days of lactation in females followed by an additional treatment until one day 

before sacrifice.

Cageside examinations were conducted at least daily for any abnormalities. Generally, food 

consumption and body weight were measured once a week. Detailed clinical observations were 

performed prior to administration and weekly thereafter. Clinicochemical and hematological 

examinations and urinalyses were performed in 5 F0 parental animals of each sex and group 

toward the end of the administration period. At the end of the administration period a functional 

observational battery was performed and motor activity was measured in 5 F0 parental males and 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

18

females per test group. At the end of the study (males: study day 31, females: study days 53 and 

56), the animals were sacrificed after a fasting period. The following organs were weighed: 

liver, kidneys, adrenal glands, testes, epididymides, prostate, seminal vesicles including 

coagulation glands, ovaries, uterus, thymus, spleen, brain, heart, and thyroid glands (with 

parathyroids). For at least the vehicle control and high dose groups, histopathological 

examinations were made on these organs plus the following: trachea, lungs, spinal cord, sciatic 

nerve, lymph nodes, stomach, intestines, bladder, and bone marrow. All gross lesions were 

examined. 

No test-substance related, relevant findings were observed at the 50 mg/kg bw/day dose level. 

At the 250 mg/kg bw/day level, the only effect observed was minimal desquamation of cecal 

epithelium in 4 out of 10 males. At the 1000 mg/kg bw/day dose, decreased food consumption 

and body weight loss in males was seen during the first study week, and significantly lower 

mean body weight during study weeks 1-3. Minimal to mild desquamation of cecal epithelium 

in 7 males, minimal to moderate increase in apoptotic cell numbers of the cecal epithelium in 

5 males and 7 females, and minimal to moderate increase in starry sky cells in the thymus of 

3 males and 2 females were observed upon pathological examinations.

The NOAEL for general, systemic toxicity of PDC was 50 mg/kg bw/day for the male F0 

parental animals based on impaired body weight data as well as pathological findings in the 

gastrointestinal tract, and 250 mg/kg bw/day for the female F0 parental animals based on 

pathological findings in the gastrointestinal tract.

5.4.4 Genetic toxicity

PDC was tested for its ability to induce chromosomal damage (clastogenicity) and spindle poison 

effects (aneugenic activity) in NMRI mice using the micronucleus test method (OECD Guideline 

474) in a GLP-compliant study (Schulz and Lansiedel, 2008). The test substance, suspended in 

corn oil, was administered twice orally (24 hours apart) to male animals at dose levels of 500, 

1,000 and 2,000 mg/kg body weight. The vehicle control was corn oil. After sacrifice at 24 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

19

hours following the last administration, the bone marrow was prepared and examined. The 

vehicle control demonstrated frequencies of micronucleated polychromatic erythrocytes within 

the historical control range, while the positive control substances provided the expected results. 

PDC did not cause any increase in the number of polychromatic erythrocytes containing either 

large or small micronuclei. No inhibition of erthyropoiesis based on the ratio of polychromatic 

to normochromatic erythrocytes was detected. Thus, PDC did not demonstrate any clastogenic 

effect or aneugenic activity in bone marrow cells in vivo. 

Bacterial reverse mutation tests were conducted under GLP with EPDC using five strains of S. 

typhimurium (TA98, TA100, TA1535, TA1537, TA1538) and E coli WP2uvrA-, both with and 

without activation. No mutagenic activity was observed (Bennett, 1986). 

5.4.5 Reproductive and Developmental Toxicity

As described in Section 5.4.3, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD Guideline 422) was conducted with PDC, 

under GLP (Buesen et al., 2010). Parental (F0) male and female Wistar rats (10 per sex per 

dose) were exposed to 50, 250, and 1000 mg/kg bw/day of the test substance via daily oral 

gavage. The vehicle control was 1% carboxymethylcellulose. F0 animals were mated 13 days 

after the beginning of treatment to produce litter (F1 generation pups). Mating pairs were from 

the same dose group. Mating was discontinued as soon as sperm was detected in the vaginal 

smear. In the reproductive portion of this study, F0 animals were examined for their reproductive 

performance including determination of the number of implantation sites and the calculation of 

postimplantation loss for all F0 females. All pups delivered from the F0 parents were examined 

as soon as possible on the day of birth to determine the total number of liveborn and stillborn 

pups in each litter, as well as macroscopically evident changes. Pups were examined daily for 

clinical symptoms. Pup body weight was determined one day after birth (PND 1) and on PND 4. 

All surviving pups (sacrificed on PND 4), all stillborn pups and those which died ahead of 

schedule were examined externally, eviscerated, and their organs were assessed macroscopically. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

20

No treatment-related effects were observed on any of the following reproductive parameters: 

male mating index, male fertility index, female mating index, female fertility index, gestation 

index, mean number of implantation sites, postimplantation loss, or live birth index. No testsubstance related effects were seen upon pup number and status at delivery, pup viability, or sex 

ratio. There were no significant findings of clinical observations or necropsy in the offspring. 

Mean pup body weights were increased in all tested groups on PND 1 and in the mid-dose group 

on PND 4. These differences were mainly caused by low pup body weight in the controls and 

were assessed as spontaneous and without biological relevance.

Thus, the NOAEL for PDC for reproductive performance and fertility in rats was 1,000 mg/kg 

bw/day. The NOAEL for developmental toxicity was also 1,000 mg/kg bw/day. 

5.4.6 Summary of Health Effects Data

The SIDS endpoints relative to health effects for PDC and EPDC are summarized in Table 5 and 

Section 7 (SIDS Data Matrix), with more detailed information provided in the Robust 

Summaries submitted with this Test Plan.

Recommendation: No additional testing is necessary on health effects endpoints. Reliable data 

are available from recent, GLP-compliant studies for PDC for the following health effects 

endpoints: repeated dose toxicity, clastogenicity, reproductive toxicity and developmental 

toxicity. Reliable data are also available for the analog, EPDC, for acute oral toxicity, acute 

dermal toxicity, and mutagenicity. Because of the high degree of structural similarity between 

the two compounds, these data are sufficient for use in read-across for the missing data for PDC, 

especially given the low toxicity and lack of mutagenic effects observed with EPDC. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

21

Table 5. Health effects information for PDC and EPDC

Ecotoxicity Endpoint1

2,3-pyridinedicarboxylic acid

(89-00-9)

2,3-pyridinedicarboxylic acid, 5-ethyl-

(102268-15-5)

Acute oral LD50 (mg/kg) 

> 500 (rat)1

(secondary citation)

> 5000 (rat)2

(Guideline study, reliable without restriction)

4251 (rat)3

(Guideline study, reliable without restriction)

Acute dermal LD50 (mg/kg)

> 200 (rabbit)1

(secondary citation)

> 2000 (rabbit)4

(Guideline study, reliable without restriction)

Repeated dose, NOAEL

50 mg/kg bw/day (males); 250 mg/kg 

bw/day (females)5

(Guideline study, reliable without 

restriction)

No data

Genetic Toxicity – in vitro No data

Negative in bacterial reverse mutation test6

(Guideline study, reliable without restriction)

Genetic Toxicity – in vivo

No clastogenic or aneugenic effects on bone 

marrow cells7

(Guideline study, reliable without 

restriction)

No data

Reproductive toxicity, NOAEL

1000 mg/kg bw/day5

(Guideline study, reliable without 

restriction)

No data

Developmental toxicity, NOAEL

1000 mg/kg bw/day5

(Guideline study, reliable without 

restriction)

No data

1

Science Lab.com MSDS

2 Lowe, 1999

3 Fischer, 1985

4

Fischer, 1985

5 Buesen et al., 2010

6 Bennett, 1986

7

Schulz and Landsiedel, 2009
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

22

6.0 Conclusions and Recommendations

The SIDS Level I endpoints for 2,3-pyridinedicarboxylic acid (PDC) are filled by a combination 

of measured and estimated data for the chemical. The adequacy of this information is further 

supported by comparable data for a closely related chemical, 2,3-pyridinedicarboxylic acid, 5-

ethyl- (EPDC). Where certain data are not available for PDC, but reliable data exist for EPDC 

(e.g., toxicity to invertebrates, acute oral and dermal toxicity, and mutagenicity), information on 

EPDC is used in a read-across manner to fill these data gaps. The use of data for EPDC to fill 

these data gaps is considered conservative, as EPDC is slightly more toxic than PDC. No 

additional testing is proposed for PDC. 
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

23

7.0 SIDS Data Matrix 

SIDS Endpoint

2,3-pyridinedicarboxylic acid

(89-00-9)

Supporting chemical: 2,3-pyridinedicarboxylic acid, 5-ethyl-

(102268-15-5)

Value Reference and Reliability1 Value Comment

Physicochemical

Melting point 185-190°C Drew, 2008a (K1) 157°C EPIWIN (K2)

Boiling point 357°C EPIWIN (K2) 380°C EPIWIN (K2)

Vapor pressure 2.67 x 10-6hPa EPIWIN (K2) 1.5 x 10-6hPa EPIWIN (K2)

Partition coefficient (Log Kow) -0.12 EPIWIN (K2) 0.92 EPIWIN (K2)

Water Solubility 9.56 g/L at 22oC Drew, 2008b (K1) 7.5 g/L EPIWIN (K2)

Environmental fate

Photodegradation (t1/2) 9.9 days (12-hour day) EPIWIN (K2) 4.8 days (12-hour day) EPIWIN (K2)

Hydrolysis Stable Stable

Fugacity < 1% air, 22.9% water, 

77.0% soil, < 1% sediment

EQC Level III (K2) < 1% air, 16.3% water, 83.6% soil, < 1% 

sediment

EQC Level III (K2)

Biodegradability 80-90% biodegradation in 

10 days (OECD 301B)

Schwarz, 2007 (K1) < 10% biodegradation in 28 days (OECD 

301A)

Schwarz, 2007 (K1)

Ecotoxicity

Acute Fish 96-h LC50 920 mg/L (estimated) ECOSAR (K2) 220 mg/L ECOSAR (K2)

Acute Invertebrate 48-h EC50 3562 mg/L (estimated) ECOSAR (K2) > 100 mg/L for Daphnia magna Mulligan, 2000 (K1)

Algal Inhibition 96-h EC50 > 100 mg/L Hoffman, 2009 (K1) 10.8 mg/L for Selenastrum 

capricornutum

Olivieri, 2000a (K1)

Toxicity

Acute Oral LD50 > 500 mg/kg (rat) MSDS (K4) > 5000 mg/kg (rat); 4251 mg/kg (rat) Lowe, 1999 (K1); Fischer, 1985

(K1; key study)

Acute Dermal LD50 > 200 mg/kg (rabbit) MSDS (K4) > 2000 mg/kg (rabbit) Fischer, 1985 (K1)

Repeated Dose, NOAEL 50 mg/kg bw/day (male);

250 mg/kg bw/day (female)

Buesen et al., 2010 (K1)
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

24

SIDS Endpoint

2,3-pyridinedicarboxylic acid

(89-00-9)

Supporting chemical: 2,3-pyridinedicarboxylic acid, 5-ethyl-

(102268-15-5)

Value Reference and Reliability1 Value Comment

Genetic Tox – In vitro Negative in bacterial reverse mutation 

test

Bennett, 1986 (K1)

Genetic Tox – In vivo Negative in micronucleus 

test

Schulz and Lansiedel, 2008

(K1)

Reproductive Toxicity, NOAEL 1000 mg/kg bw/day Buesen et al., 2010 (K1)

Developmental Toxicity, NOAEL 1000 mg/kg bw/day Buesen et al., 2010 (K1)

1 Reliability refers to the Klimisch score: 

K1 = reliable without restriction

K2 = reliable with restriction

K3 = not reliable

K4 = not assignable
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

Draft

25

8.0 References

This list of references is for studies as cited in Sections 1 through 7, while a complete list of all 

data sources reviewed in the development of the Test Plan and Robust Summaries for

2,3-pyridinedicarboxylic acid can be found in the Robust Summaries.

Buesen, R., Strauss, V., Treumann, S., Fabian, E., van Ravenzwaay, B. 2010. 2,3-Pyridine 

Dicarboxylic Acid (PDC) Combined Repeated Dose Toxicity Study with the 

Reproduction/Developmental Toxicity Screening Test in Wistar Rats Oral Administration 

(Gavage). BASF DocID 2010/1173791. BASF SE, 67056 Ludwigshafen, Germany.

Bennett, W.J. 1986. Acute Toxicity and Mutagenicity Testing of CL 271,197. American 

Cyanamid Company.

Drew, M. 2008a. Determination of Melting Point of 2,3-pyridine dicarboxylic acid by OECD 

Guideline for the Testing of Chemicals #102 Capillary Tube in a Liquid Bath Method. BASF 

DocID 2008/7009356. BASF Corporation, 26 Davis Drive, Research Triangle Park, NC 27709.

Drew, M. 2008b. Determination of Water Solubility of 2,3-pyridine dicarboxylic acid by OECD 

Guideline for the Testing of Chemicals #105 Flask Method. BASF DocID 2008/7009357. BASF 

Corporation, 26 Davis Drive, Research Triangle Park, NC 27709.

EPA, 1999a. The use of structure-activity relationships (SAR) in the High Production Volume 

Chemicals Challenge Program. At http://www.epa.gov/chemrtk/sarfinl1.htm.

EPA. 1999b. Determining the adequacy of existing data. Available at: 

http://www.epa.gov/chemrtk/pubs/general/datadfin.htm.

Fischer, J.E. 1985. Toxicity Report Data. Animal Industry R/D. Agricultural Research Division. 

American Cyanamid Co. P.O. Box 400, Princeton, NJ 08540. Report# A85-79.

Hoffman, F. 2009. Effect of Reg. No. 4036318 (Metabolite and Intermediate of BAS 693 H, 

Imazapyr) on the Growth of the Green Alga, Pseudokirchneriella subcapitata. BASF DocID 

2009/1011444, BASF SE, BASF Agricultural Center Limburgerhof, Crop Protection Division, 

Ecology and Environmental Analytics, P.O. Box 120, Limburgerhof, Germany. 

HSDB, Hazardous substances data banhttp://toxnet.nlm.nih.gov/cgibin/sis/search/f?./temp/~MSAgqg:1. Last revision 2007-10-11.

Klimisch, H.J., Andreae, M. And Tillmann, U., 1997. A systematic approach for evaluating the 

quality of experimental toxicological and ecotoxicological data. Regulatory Toxicol. and 

Pharmacol. 25:1-5.
HPV Robust Summaries and Test Plan – 2,3-pyridinedicarboxylic acid

Draft

26

Lowe, C.A. 1999. Oral LD50 Study in Albino Rats with CL 271197. Toxicology Study Report 

Number A98-100. American Cyanamid Company. Agricultural Products Research Division. 

Toxicology Department. P.O. Box 400. Princeton, NJ 08543-0400.

Mackay, D., DiGuardo, A., Paterson, S., and Cowan, C. et al.. 1996. Evaluating the 

Environmental Fate of a Variety of Types of Chemicals Using the EQC Model. Envir. Toxicol. 

Chem. 15:1627-37.

Material Safety Data Sheet. Quinolinic Acid MSDS. Prepared By: Sciencelab.com, Inc. 14025 

Smith Rd, Houston, TX 77369.

Mulligan, E. 2000. Acute Toxicity of CL 271,197 to Daphnia magna Under Static Test 

Conditions. American Cyanamid Company. Global Agricultural Products Research Division, 

Princeton, NJ 08543-0400. Performing Laboratory: American Cyanamid Company, 

Ecotoxicology Laboratory Facility, Global Laboratory Products Research Division. P.O. Box 

400, Princeton, NJ 08543-0400. Laboratory Project Identification ETX-99-132.

Naik, N.M., Jackson, R.B., Stokes, J., and Swaby, R.J. 1972. Microbial degradation and 

phytotoxicity of picloram and other substituted pyridines. Soil Biol. Biochem; 4:313-323.

Olivieri, C.E, Boeri, R.L., Ward, T.R. 2000a. Effect of CL 271,197 on the Growth of 

Selenastrum capricornutum. American Cyanamid Company. Report Number ETX-99-133. 

Performing Laboratory: T.R. Wilbury Laboratories, Inc. 40 Doaks Lane, Marblehead, MA, 

01945, Study No. 1724-AC.

Olivieri, C.E, Boeri, R.L., Ward, T.R. 2000b. Effect of CL 271,197 on the Growth of Lemna 

gibba G3. American Cyanamid Company. Report Number ETX-99-131. Performing Laboratory: 

T.R. Wilbury Laboratories, Inc. 40 Doaks Lane, Marblehead, MA, 01945, Study No. 1725-AC.

Schulz, M. and Landsiedel, R. 2008. 2,3-Pyridine Dicarboxylic Acid (PDC) Micronucleus Test 

in Bone Marrow of the Mouse. BASF DocID 2008/1087535. BASF Corporation, 63461 

Missouri, USA. 

Schwarz, H. 2007. Determination of the Biodegradability in the DOC Die-Away Test, Report. 

BASF Aktiengesellschaft. Experimental Toxicology and Ecology. 67056 Ludwigshafen, 

Germany. Project No.: 21G0188/063133.

Schwarz, H. 2009. 2,3-Pyridine Dicarboxylic Acid (PDC) Determination of the Biodegradability 

in the CO2-Evolution Test. BASF DocID 2009/1009298. BASF Corporation, 63461 Missouri, 

USA. 

Science Lab.com, Quinolinic Acid MSDS.

Sims, G.K., and Sommers, L.E. 1985. Degradation of pyridine derivatives in soil. J. Environ. 

Qual. 14:580-4.

Sims, G.K., and Sommers, L.E. 1986. Biodegradation of pyridine derivatives in soil suspensions. 

Environmental Toxicology and Chemistry; 5:503-509.