3-methylpyridine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

50 mg/kg bw/day

Additional information

Pyridine was investigated in an OECD 421 reproductive toxicity 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 in 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.

Short description of key information:
A category of pyridine and methyl pyridine derivatives is comprised of: pyridine, 2-methylpyridine, 3-methylpyridine and 4-methylpyridine. The basis of the category is structural similarity (based on the pyridine unsaturated ring structure) and similar physical properties, environmental fate and ecotoxicity, and mammalian toxicity. Similar toxicological properties derive from similar physical-chemical properties and common pathways of metabolism and elimination among all members of the category. This category is accepted by the U.S. Environmental Protection Agency (EPA). In an OECD 421 Reproductive Toxicity test on pyridine, no reproductive effects were observed at the highest dose tested. This is supported by data from chronic studies of pyridine, where no (nontumor ) pathology was observed in reproductive organs.

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 developmental toxicity 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

Dose descriptor:

NOAEL

25 mg/kg bw/day

Additional information

A developmental toxicity study (OECD 421) was undertaken on pyridine, a member of the pyridine derivatives category. 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 developmental findings attributable to pyridine. Under the conditions of this study, a parental No Observed Effect Level (NOAEL) was not established (< 12 mg/kg bw/d) due to the increased liver weights observed in all treatment groups. The NOEL for developmental 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 developmental toxicity at doses several-fold higher than doses causing toxicity in adult animals.

Justification for classification or non-classification

Pyridine, a structural analogue to 3 -methylpyridine based on a chemical category, has been adequately studied in animal protocols, demonstrating no targeted toxicity to the reproductive system except at high doses causing parental toxicity. This substance is not classified as a reproductive toxicant or a CMR (carcinogen, mutagen or reproductive toxicant).