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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
225
Modified dose descriptor starting point:
NOAEC
Value:
555 mg/m³
Explanation for the modification of the dose descriptor starting point:
no r-t-r.
AF for dose response relationship:
3
Justification:
Less robust study (14 days duration) than 28- or 90-day
AF for differences in duration of exposure:
6
Justification:
less than 28
AF for interspecies differences (allometric scaling):
1
Justification:
accommodated in inhalation calculations
AF for other interspecies differences:
2.5
Justification:
pharmacodynamic
AF for intraspecies differences:
5
Justification:
individual
AF for the quality of the whole database:
1
Justification:
adequate
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
0.33
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.14 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Absorbed through skin.
AF for dose response relationship:
1
Justification:
DR shown in chronic toxicity study
AF for differences in duration of exposure:
1
Justification:
2-year lifetime study
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
pharmadynamic
AF for intraspecies differences:
5
Justification:
individual
AF for the quality of the whole database:
1
Justification:
full dataset for oral toxicity
AF for remaining uncertainties:
1
Justification:
no others
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
0.33
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The chronic oral/dermal systemic DNEL is 0.14 mg/kg bw/d, based on a NOAEL of 7 mg/kg bw/d from the 2-year NTP chronic bioassay of pyridine in F344 rats, and an AF of 50. 

 

A sub-acute inhalation study of beta-picoline (3-methylpyridine, a member of the Pyridine and pyridine derivatives category), of 14 days duration in rats (Chen and Krauss, 1984) was selected. The LOAEC was 290 ppm, equivalent to 1105 mg/m3. This was determined to be the NOAEC, because a 13 day recovery period demonstrated that effects on liver weight were completely reversible. To the NOAEC are applied two dose modifiers of 0.75 (to convert from a 6 h test exposure to an 8 h workday) and 0.67 (to convert from a resting activity level to an activity level of light exertion). This produces a modified dose descriptor of 555 mg/m3, to which is applied an AF of 225 (2.5 for interspecies (no allometric scaling factor is indicated (Table 8.4, ECHA TGD R.8, 2008)), 5 for intraspecies, 6 for duration, 1 for complete dataset, and 3 for a Dose-Response AF due to a less robust study design and pathology assessment in the 14 day study, compared to a 28-day study.) The DNEC is 2.5 mg/m3. This applies to all members of thePyridine and Pyridine Derivatives Category,an established category accepted by the U.S. Environmental Protection Agency. Category members include pyridine, 2-methylpyridine, 3-methylpyridine and 4-methylpyridine. In support of this DNEC are the results of an additional inhalation study of pyridine toxicity (Watanabe, et.al, 1979), part of the U.S.Voluntary HPV submission package on the Pyridine and Pyridine Derivatives Category, but to which legal access was not able to be obtained. A robust summary of the study is provided as an attachment in IUCLID5, and indicates that the NOAEC in CD rats after a 6-month inhalation study (6 hr/day, 5 days/week) is >100 ppm or 323 mg/m3. This results in a DNEC of 6.5 mg/m3, and suggests that the use of the Chen and Krauss study, with the selected AFs, provides values which are sufficiently conservative and valid for determining acceptable levels of exposure.

 

As pyridine is an irritant to the skin and eye, local effects will be evaluated in a qualitative manner. Risk management measures, such as gloves and goggles/safety glasses, are recommended to minimize the risk of adverse effects of local exposures to pyridine. 

The data are appropriate to apply from these two structural analogues to the registered substance, 4 -methylpyridine.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
450
Modified dose descriptor starting point:
NOAEC
Value:
276 mg/m³
Explanation for the modification of the dose descriptor starting point:
no r-t-r
AF for dose response relationship:
3
Justification:
DR Less robust study (14 days duration) than 28- or 90-day
AF for differences in duration of exposure:
6
Justification:
less than 28-day duration
AF for interspecies differences (allometric scaling):
1
Justification:
per ECHA guidance
AF for other interspecies differences:
2.5
Justification:
pharmacodynamic
AF for intraspecies differences:
10
Justification:
individual variation
AF for the quality of the whole database:
1
Justification:
adequate
AF for remaining uncertainties:
1
Justification:
no others
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.07 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 450
Modified dose descriptor starting point:
NOAEL
Value:
7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no r-t-r
AF for dose response relationship:
1
Justification:
DR seen in chronic toxicity study
AF for differences in duration of exposure:
1
Justification:
2-year lifetime study
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
pharmacodynamic
AF for intraspecies differences:
10
Justification:
individual
AF for the quality of the whole database:
1
Justification:
full dataset
AF for remaining uncertainties:
1
Justification:
no others
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.07 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no r-t-t
AF for dose response relationship:
1
Justification:
DR seen in chronic toxicity study
AF for differences in duration of exposure:
1
Justification:
2-year lifetime study
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
pharmacodynamic
AF for intraspecies differences:
10
Justification:
individual
AF for the quality of the whole database:
1
Justification:
full data set for oral exposure
AF for remaining uncertainties:
1
Justification:
no others
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There are no applications of pyridine or picolines involving the general population, to the knowledge of the manufacturer/importer. The oral DNEL is generated in order to assess risk for man via the environment. Any chemical exposure from the environment would to diluted material, not associated with eye irritation. While the general population may come in contact with pyridine as a component of cigarette smoke, food components or break-down products of flavours/food additives, or pharmaceuticals, these exposures are not derived from industrial sources of pyridine. They are outside the scope of REACH and are considered under the jurisdiction of other regulations. Risk assessment for the general population will not be considered here.

The data are appropriate to apply from two structural analogues to the registered substance, 4 -methylpyridine.