Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
500 mg/kg bw/day
Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
37 595 mg/m³
Additional information

An OECD 422 study in rats (via the oral route) is available for TPnB-highers. No fertility effects were observed in this study. A NOAEL for fertility effects of 500 mg/kg bw/day has been established. No 2-generation reprotox study is available for TPnB-highers. However, the structurally related propylene glycol methyl ether (PGME) has undergone this type of testing. PGME is closely related in molecular structure and physicochemical properties and thus, the potential for toxicological effects. The category of glycol ethers are liquids with comparable physical chemical properties. Increasing boiling point and vapor pressure are consistent with increasing molecular weight. No major differences in the toxicological profile have been observed between propylene glycol ethers e.g. mono-, di- and tri-propylene glycol methyl ethers and mono-, di- and tri-propylene glycol n-butyl ethers. In a 2-generation reproductive toxicity study with PGME via the inhalation route no direct reproductive toxicity was observed at doses up to 3000 ppm. Ovarian weights were decreased (with accompanying atrophy) at 3000 ppm but not 1000 ppm, considered secondary to severe maternal weight loss of 21% at 3000 ppm. PGME did not cause any reduction in sperm counts or mobility.


Short description of key information:
A two-generation inhalation reproduction study with propylene glycol methyl ether (PGME) in Sprague-Dawley rats is available. The study was conducted under GLP and according to OECD guideline 416. In addition, a GLP study (oral gavage in rats) according to OECD guideline 422 is available for TPnB-highers.

Effects on developmental toxicity

Description of key information
An OECD 422 study in rats is available for TPnB-highers. In addition, available data on structural analogues propylene glycol butyl ether (PnB), dipropylene glycol butyl ether (DPnB) and tripropylene glycol methyl ether (TPGME) is used for read-across.
For PnB and DPnB dermal developmental toxicity study in rats according to OECD guideline 414 are available. For TPGME an OECD 414 inhalation developmental toxicity study in rats is available.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
500 mg/kg bw/day
Effect on developmental toxicity: via dermal route
Dose descriptor:
NOAEL
880 mg/kg bw/day
Additional information

An OECD 422 study in rats (via the oral route) is available for TPnB-highers. No developmental toxicity effects were observed in this study. A NOAEL for developmental effects of 500 mg/kg bw/day has been established. No developmental toxicity study according to OECD guideline 414 is available for TPnB-highers. However, the structurally related substances propylene glycol butyl ether (PGBE), dipropylene glycol n-butyl ether (DPGBE) and tripropylene glycol methyl ether (TPGME) have undergone this type of testing as well as a number of other propylene glycol ethers. PGBE, DPGBE, TPGME and TPnB-highers are closely related in molecular structure and physicochemical properties and thus, the potential for toxicological effects. They are liquids with similar physical chemical properties. Increasing boiling point and vapor pressure are consistent with increasing molecular weight. No major differences in the toxicological profile have been observed between other glycol ethers families (e.g. mono-, di- and tri-propylene glycol methyl ethers). The results of propylene glycol ethers were consistently negative in developmental toxicity studies. PGBE, DPGBE and TPGME are not maternally toxic, embryo- or fetotoxic, or teratogenic in rats or rabbits. Hence, the developmental toxicity studies on PGBE, DPGBE and TPGME are used to fulfill the developmental toxicity requirement for TPnB-highers by read-across.

Justification for classification or non-classification

Since TPnB-highers has undergone a repeated dose toxicity and reprotox testing in an OECD 422 study, conclusions can be drawn regarding damage to reproductive organs. Results from the study indicate that TPnB-highers did not cause toxicity to the testes. Specifically, no reduction in testicular weight, no damage to the sperm or sperm-producing cells, and no damage to the epididymis or seminiferous tubules were reported. Likewise, no damage to female reproductive organs was found. In addition, read-across data from another P-series glycol ether (2-generation reprotox study on PGME and several developmental toxicity studies, e.g. with PGBE, DPGBE and TPGME) are available to address these endpoints. No treatment-related effects on reproductive parameters or developmental effects were observed with PGME. Therefore, TPnB-highers should not be classified for reproductive toxicity or developmental effects.