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Key value for chemical safety assessment

Effects on fertility

Description of key information
No other studies available
Effect on fertility: via oral route
Dose descriptor:
NOAEL
300 mg/kg bw/day
Additional information

Groups of 12 male and 12 female Crl:CD(SD) rats were administered Dipropylene Glycol n-Propyl Ether (DPnP) daily, by gavage at dose levels of 0 (control), 100, 300, or 1000 mg/kg/day. Females were dosed once daily for two weeks prior to breeding, through breeding (two weeks), gestation (three weeks), and lactation up to postpartum day 4.

Females were necropsied on postpartum day 5. Males were dosed two weeks prior to breeding and continuing through breeding (two weeks) until necropsy (test day 29). Effects on reproductive function as well as general toxicity were evaluated. In addition, postmortem examinations included a gross necropsy of the adults with collection of organ weights and histopathologic examination of tissues. Litter size, pup survival, sex, body weight, and the presence of gross external abnormalities were also assessed.

Administration of 1000 mg/kg/day of DPnP resulted in treatment-related parental toxicity in males and females consisting of increases in the incidence of hepatocellular hypertrophy and corresponding increases in absolute and relative liver weights. In addition, absolute and relative kidney weights were increased in males and females at this dose level. Microscopic examination of the kidneys revealed hyaline droplet formation in the proximal renal tubules of males given 1000 mg/kg/day, but there were no treatment-related histopathologic findings in the kidneys of high-dose females. Transient, excess salivation was noted in the majority of high-dose males and females immediately after dosing, but was considered to be a local response and of no toxicological significance.

Accompanying the parental toxicity at 1000 mg/kg/day was a slight, treatment-related increase in post implantation loss, along with a corresponding slight increase in gestation survival and very slight decrease in litter size. One high-dose female also had a difficult birth and retained placentae, although the relationship of this finding to treatment is equivocal. There was no parental or reproductive toxicity at 300 or 100 mg/kg/day.

Based on these results, the no-observed-effect level (NOEL) for parental and reproductive toxicity and was 300 mg/kg/day.


Short description of key information:
Toxicity to reproduction in rats, OECD 421

Effects on developmental toxicity

Description of key information
Developmental toxicity study in rabbits, OECD 414
Effect on developmental toxicity: via dermal route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

The objective of the study was to determine the potential maternal toxicity (local and systemic) and/or prenatal developmental toxicity of the test article, dipropylene glycol n-propyl ether (DPnP), when administered by dermal exposure to pregnant rabbits throughout the period of major organogenesis up to a limit dose of 1000 mg/kg/day and to determine a NOAEL (no-observed-adverse-effect level) for maternal toxicity and developmental toxicity. The Dermal route was selected as this is the most relevant route for human exposure to this substance.

All animals survived to the scheduled necropsy. Slight to severe scaling and slight fissuring was noted for a majority of animals in the 1000 mg/kg/day group. The incidence of these findings were highest mid-way through dosing, and decreased in severity and incidence generally throughout the remainder of the study. The control, 500 and 750 mg/kg/day groups also experienced slight scaling, but the incidence was greatly reduced compared to the 1000 mg/kg/day group. Moderate erythema was noted in 1 and 4 females in the 750 and 1000 mg/kg/day groups, respectively. Slight erythema was noted in all treatment groups, with the highest occurrence in the 1000 mg/kg/day group. The incidence of very slight erythema (barely perceptible) was similar between the control and 500 mg/kg/day group; however, this finding was noted up to approximately twice as often in the 750 and 1000 mg/kg/day groups, respectively, throughout the

treatment period. Very slight to slight edema was noted for multiple females in the 500, 750 and 1000 mg/kg/day groups, compared to a single occurrence of very slight edema in the control group; no dose-related trend was evident. No maternal systemic toxicity (clinical observations, body weight, food consumption, macroscopic findings or liver weights) was observed at any dosage level in this study. Dermal irritation (local toxicity) was transiently observed at all dosage levels. Intrauterine growth and survival in the test article-treated groups were similar to the control group. There were no test article-related malformations or developmental variations observed in any fetus evaluated in this study.

Based on the results of this study, the dermal application of 1000 mg/kg/day (the limit dose based on OPPTS 870.3700 Guidelines) was considered to be the no-observed-adverse-effect level (NOAEL) for maternal systemic toxicity; however, dermal irritation (local toxicity) was transiently observed at all dosage levels. A dosage level of 1000 mg/kg/day was considered to be the NOAEL for prenatal development when DPnP was administered by dermal exposure to pregnant rabbits.

Toxicity to reproduction: other studies

Additional information

No other studies available

Justification for classification or non-classification

There were no effects observed in the dermal developmental study at any dose level. In the reproductive screening study there were some minor effects at the high dose on pup survival and some evidence of post implantation loss, however the effects were very minor and accompanied some maternal toxicty. Therefore based on the results of the studies and Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, dipropylene glycol n-propyl ether will not be classified for reproduction toxicity.