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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 route-to-route
AF for dose response relationship:
3
Justification:
Less robust study (14 days duration) rather than 28- or 90-day study
AF for differences in duration of exposure:
6
Justification:
less than 28 days
AF for interspecies differences (allometric scaling):
1
Justification:
accommodated in starting dose descriptor calculations
AF for other interspecies differences:
2.5
Justification:
pharmacodynamic
AF for intraspecies differences:
5
Justification:
individual differences among workers
AF for the quality of the whole database:
1
Justification:
adequate
AF for remaining uncertainties:
1
Justification:
see AF for dose-response
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
assume 100% skin absorption
AF for dose response relationship:
1
Justification:
Dose response 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:
pharmacodynamic (remainder)
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:
uncertainty is accommodated in other AF
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:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The DNELs calculated herein apply to all members of the Pyridine 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. The basis of the category is a common functional group, a pyridine, and the category members display consistent physico-chemical properties, environmental fate characteristics and toxicity test results.

A sub-acute inhalation study of beta-picoline (3-methylpyridine) of 14 days duration in rats (Chen and Krauss, 1984) was selected for the inhalation risk calculation. 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 (per ECHA, 2010, Information Requirements and the Chemical Safety Assessment, R.8 and Appendix 8-8). An additional AF of 3 for the Dose-Response is applied to the standard AFs, 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.  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 detailed textual summary of the study is provided as an attachment in the IUCLID record, 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, higher than our value of 2.5 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.

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.  

As 2-methyl pyridine is classified for acute oral toxicity, skin corrosion, eye irritation and respiratory effects, 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 derivatives.

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 route-to-route
AF for dose response relationship:
3
Justification:
Dose response less robutst (14 days rather than 28 days)
AF for differences in duration of exposure:
6
Justification:
less than 28 days
AF for interspecies differences (allometric scaling):
1
Justification:
no AF applied
AF for other interspecies differences:
2.5
Justification:
pharmacodynamic (remainder)
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 AF applied
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):
100
Modified dose descriptor starting point:
NOAEL
Value:
7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assume 100% dermal absorption
AF for dose response relationship:
1
Justification:
Dose response 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 (remainder)
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 AF applied
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:
0.7 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 route-to-route
AF for dose response relationship:
1
Justification:
Dose response 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 (remainder)
AF for intraspecies differences:
10
Justification:
individual variability
AF for the quality of the whole database:
1
Justification:
adequate
AF for remaining uncertainties:
1
Justification:
no AF applied
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 picolines or pyridine (from industrial sourcing) involving the general population, to the knowledge of the manufacturer/importer. Theoretical DNELs are generated for inhalation and dermal chronic systemic exposures. The oral DNEL is generated in order to assess risk for man via the environment. Any chemical exposure from the environment would be to diluted material, unlikely to result in toxicity or irritation. 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; however, these exposures are unlikely to be derived from industrial sources of pyridine or 2-methylpyridine. They are outside the scope of REACH and are considered under the jurisdiction of other European regulations.