Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Single generation OECD415 study, oral route: NOAEL (reproductive effects) > 1000mg/kgbw/day
Multiple generation OECD416 study, inhalation route (surrogate substance), NOEC (reproductive effects) > saturated vapour concentration.by extrapolation.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Species:
rat
Additional information

There is no multi-generation reproductive toxicity study available on this substance. In a single generation OECD415 guideline oral study, Dipropylene Glycol Monoethyl Ether was not a reproductive toxicant in the rat at dosages greater than those demonstrably toxic in male rats . The NOAEL (all reproductive measures) and in females was 1000 mg/kg bw/day, the highest dose tested. The toxic NOAEL in males (only) was 50 mg/kg bw/day, a dosage that evokes male unique hydrocarbon nephropathy at a dose of 225mg/kg and above. (It should be noted that this effect was also noted in a repeat dose study but effects were milder and shown to be fully reversible.)

In a guideline and GLP study, the reproductive toxicity of methoxypropanol, a structural analogue of ethoxypropoxypropanol, was studied in male and female SD rats exposed by inhalation to 0, 300 1,000 or 3,000 ppm vapours for 10 days prior to mating and 7 d/wk during mating, gestation and lactation for 2 generations. Marked parental toxicity was seen at 3,000 ppm, as evidenced by changes in various organ and body weights (relative/absolute) of the first and second generation males and females, in particular of the testes and ovaries. In females, toxicity was accompanied by decreased fertility, lengthened oestrous cycle, decreased ovarian weight and histopathological ovarian atrophy. Embryotoxicity and foetotoxicity occurred only at maternally toxic doses. No reproductive/neonatal effects were observed at 1000 ppm, a concentration which caused less marked , but significant body weight effects without sedation. Based on these findings the NOEL for parental toxicity was 300ppm and for reproductive/neonatal effects along with more severe parental toxicity was 1000 ppm. Equivalent airborne concentrations of ethoxypropoxypropanol are 6.63 and 1.99 mg/L, respectively. It should be noted that the saturated vapour concentration of ethoxypropoxypropanol is ~3.4mg/l and therefore it can be concluded that the NOAEL for reproductive toxicity cannot be reached by inhalation exposure to ethoxypropoxypropanol. It should also be noted that the effects seen in the second generation of the test using methoxypropanol were identical to those seen in the first generation, indicating that the results from a single generation study are sufficient to predict toxicity to reproduction for this class of substances and therefore the single generation study using ethoxypropoxypropanol should be sufficient to predict toxicity to this end point.

Based on the high level of understanding of metabolism and toxicity of glycol ethers, it is reasonable to expect the toxicity of ethoxypropoxypropanol to be of a lower order than methoxypropanol; systemic toxicity decreases as the number of propylene oxide units and alkyl chain length increases (ECETOC 2005). Accordingly, it is believed that this information for the reproductive toxicity of methoxypropanol provides a useful indication of the worst case reproductive toxicity likely to be seen with the propylene oxide based glycol ethers. See summary of toxicokinetics of glycol ethers (7.1.1) for more information. Therefore one can confidently predict that if methoxypropanol is not toxic to reproduction, neither will ethoxypropoxypropanol, the subject of this registration.

Based on the available data, it can be concluded with some certainty that ethoxypropoxypropanol does not exhibit specific toxicity to reproduction.

Reference

ECETOC (2005) The toxicology of glycol ethers and its relevance to man (4th ed), Technical report 95, ECETOC, Brussels.

Effects on developmental toxicity

Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Species:
other: rat and rabbit
Additional information

There is no developmental toxicity data available on ethoxypropoxypropanol.

In a guideline and GLP developmental toxicity study in rats, whole body inhalation exposure to ethoxypropanol, a close structural analogue of ethoxypropoxy propanol, at vapour at concentrations up to 2000 ppm on Days 6-15 of gestation did not produce evidence of developmental effects (based on uterine and litter data, and foetal development).  Reduced weight gain and clinical signs were noted in maternal animals exposed to 450 ppm or 2000 ppm.  No effects were noted in maternal animals exposed to 100 ppm.  Based on these results the following NOAECs for developmental toxicity in the rat are established for ethoxypropanol vapour:

NOAEC (maternal) >= 100 ppm (0.425 mg/L, equivalent to 0.463mg/l of ethoxypropoxy propanol)

NOAEC (developmental) >= 2000 ppm (8.5 mg/L, equivalent to 13.26mg/l of ethoxypropoxy propanol)  It should be noted that the saturated vapour concentration of ethoxypropoxypropanol is ~3.4mg/l.

 

In a guideline and GLP developmental toxicity study in rabbits, whole body inhalation exposure to ethoxypropanol, a close analogue of ethoxypropoxy propanol, at vapour concentrations up to 1200 ppm on Days 6-18 of gestation did not produce evidence of developmental effects (based on uterine and litter data, and foetal development).  A slight reduction in mean food consumption and an initial retardation in body weight gain (gestation days 6 – 10) was seen in maternal animals exposed to 1200 ppm.  No effects were noted in maternal animals exposed to 100 or 350 ppm.  Based on these results the following NOAECs for developmental toxicity in the rabbit are established for ethoxypropanol vapour:

NOAEC (maternal) = 350 ppm (1.49 mg/L), equivalent to 2.32 mg/l of ethoxypropoxy propanol).

NOAEC (developmental) > 1200 ppm (5.1 mg/L, equivalent to 7.8mg/l of ethoxypropoxy propanol). It should be noted that the saturated vapour concentration of ethoxypropoxypropanol is ~3.6mg/l so on this basis it can be concluded that it is not possible to reach a concentration by inhalation that would cause developmental effects.

 

Based on the known pattern of toxicity of glycol ethers, toxicity decreases as the number of propylene oxide units increase (ECETOC 2005) Therefore one can confidently predict that if ethoxypropanol is not developmentally toxic, neither will ethoxypropoxypropanol, the subject of this registration.)

Reference

ECETOC (2005) The toxicology of glycol ethers and its relevance to man (4th ed), Technical report 95, ECETOC, Brussels.

Justification for classification or non-classification

Based on the available data, this substance does not warrant classification either for reproductive or developmental toxicity effects.