2-methylpyridine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

50 mg/kg bw/day

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A category of pyridine and alkyl pyridine derivatives is comprised of pyridine (CAS 110 -86 -1), 2-methylpyridine (CAS 109 -06 -8), 3-methylpyridine (CAS 108 -99 -6) and 4-methylpyridine (CAS 108 -89 -4). The foundation of the category is a common functional group (the pyridine unsaturated ring structure) and similar physico-chemical properties, environmental fate and toxicity, and mammalian toxicity. Similar toxicological properties derive from physico-chemical parameters and common pathways of metabolism and elimination among all members of the category. Three of four members of this category have harmonized classification and labelling. Read-across for non-harmonized endpoints is adequate for risk assessment purposes.

Pyridine was investigated in an OECD 421 study using oral gavage as the route of administration of doses of 12, 25 and 50 mg/kg bw/d in rats. Generalized toxicity was observed at all doses, as noted by mild elevations in liver weights. There were no adverse effects on epididymides and testes of the males, nor of ovaries or uterus in the females, nor were there obvious effects of treatment on mating performance, fertility or duration of gestation. The NOAEL was > 50 mg/kg bw/d, the highest dose tested. This study indicates that there is no adverse reproductive toxicity at doses several-fold higher than doses causing generalized toxicity in the adults. In 13 and 14 week studies of pyridine or 3 -methylpyridine in the drinking water of rats and mice (NTP studies), the only finding was a possible alteration in the length of the estrus cycle, which may be a result of generalized toxicity or decreased water consumption.

Short description of key information:
In an OECD 421 test on pyridine, no reproductive effects were observed at the highest dose tested, while a NOAEL was unable to be obtained in adult animals due to the occurrence of liver weight changes. Chronic studies of pyridine and 3-methylpyridine, a category member, show possible estrus cycle changes which may be due to other methodologic factors.

Justification for selection of Effect on fertility via oral route:
experimental result of a guideline study

Effects on developmental toxicity

Description of key information

A developmental toxicity study (OECD 421) was undertaken on pyridine at doses of 0, 12, 25 and 50 mg/kg bw/d in CD rats.  No NOAEL was established due to increased liver weights in all exposed groups.  Fewer pups survived to day 4 of lactation in the 50 mg/kg bw/d group.  No teratogenic effects were noted.  The NOAEL for reproduction was 25 mg/kg bw/d, several fold higher than doses causing toxicity in the dams or adult males.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

25 mg/kg bw/day

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

A category of pyridine and alkyl pyridine derivatives is comprised of pyridine (CAS 110 -86 -1), 2-methylpyridine (CAS 109 -06 -8), 3-methylpyridine (CAS 108 -99 -6) and 4-methylpyridine (CAS 108 -89 -4). The foundation of the category is a common functional group (the pyridine unsaturated ring structure) and similar physico-chemical properties, environmental fate and toxicity, and mammalian toxicity. Similar toxicological properties derive from physico-chemical parameters and common pathways of metabolism and elimination among all members of the category. Three of four members of this category have harmonized classification and labelling. Read-across for non-harmonized endpoints is adequate for risk assessment purposes.

A developmental toxicity study (OECD 421) was undertaken on pyridine. Doses of 0, 12, 25 and 50 mg/kg bw/d were administered by oral gavage to male rats at doses for 2 weeks prior to mating, and to females for 2 weeks prior to mating and throughout the gestation and lactation periods. There were no adverse reproductive findings attributable to pyridine. Under the conditions of this study, a parental No Observed Effect Level (NOAEL) was not established (< 25 mg/kg bw/d) due to the increased liver weights observed in all treatment groups. The NOEL for reproductive parameters was considered to be 25 mg/kg bw/day based on decreased mean numbers of live pups per litter on days 1 and 4 of lactation for the 50 mg/kg bw/day dose group. This study indicates that there is no adverse reproductive toxicity at doses several-fold higher than doses causing toxicity in adult animals.

This data does not support a scientific need for the conduct of a two-generation reproductive toxicity test, which uses hundreds of live animals. In Regulation (EC) No. 1907/2006, Chapter 1, Article 25 .1, it is stated that “ in order to avoid animal testing, testing on vertebrate animals for the purposes of this Regulation shall be undertaken only as a last resort.”

Justification for selection of Effect on developmental toxicity: via oral route:
experimental result of a guideline study

Justification for classification or non-classification

Pyridine and its methyl derivatives have been adequately studied in animal protocols and there is no targeted toxicity to the reproductive system. The registered substance is not classified as a reproductive toxicant.