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EC number: 203-529-7 | CAS number: 107-88-0
In a five generation study with embedded continuous breeding study no effects on fertility were observed in 4 generations up to the highest concentration tested (24% in diet; 12000 mg/kg bw/d). The pregnancy rate of F1A rats decreased during 5 successive mating cycles, no pubs were obtained at the highest concentration of the fifth series of litters (F2E). Therefore, the mid dose group (10% in diet; 5000 mg/kg bw/d) was selected as NOAEL. No effects on fertility were observed in additional studies of lower reliability at comparable dose-levels.
Body weight gain of male rats is presented in the following table:
Twenty five animals of both sexes were fed either control diet or diet supplemented with 1,3-butylene glycol at dose levels of 5, 10 or 24% of the diet (2500, 5000 or 12000 mg/kg bw/d). Treatment with the test item had no influence on reproduction and lactation parameters for four of five generations of dams and pups. The pregnancy rate of F1A rats decreased during five successive mating cycles: no pups were obtained at the high-dose level group of the fifth series of litters (F2E generation). Excluding this group, the viability of F2 generation pups revealed no significant differences between litters or between control and test groups. Body weight gains of male rats in all four generations were slightly depressed with an apparent dose relationship. Body weight gain of females was not affected (Hess et al., 1981).
The study indicates that fertility is not impaired through 1,3 -butylene glycol exposure up to 10% in diet (5000 mg/kg bw/d).
Effects on fertility were investigated in rats which received up to 24% 1,3 -butylene glycol in the diet (12000 mg/kg bw/d). No effects were observed in 4 generations of a five generation study. But the pregnancy rate of F1A rats decreased during 5 successive mating cycles and no pubs were obtained at the highest concentration of the fifth series of litters (2FE). Additionally, in this study a dose dependent influence of the test item on the body weight gain of male rats was observed (Hess et al., 1981). The highest dose (24%, 12000 mg/kg bw/d) was therefore regarded as LOAEL and the mid dose (10% in diet, about 5000 mg/kg bw/d) as NOAEL. Instead of some shortcomings in the documentation, this well planned and performed study was judged to be reliable and was selected as key study for this endpoint.
The findings of the key study are supported by the data from two other multigeneration studies, which did not report an impairment of fertility by 1,3 -butylene glycol concentrations of 20% or 24% in diet (10000 or 12000 mg/kg bw/d, respectively; Dymsza and Adams, 1969; Celanese, 1974). However, due to their incomplete documentation these studies were judged to be of lower reliability (RL3). In a multigeneration study in rats which received about 5000 mg 1,3 -BD/kg bw on two days per week no impairment of fertility or reproductive disturbances were observed (Meyer, 1951).
Taking into account all information available for 1,3 -butylene glycol there is only single evidence from the continuous breeding study in rats which revealed adverse effects on fertility in the fifth litter of the F1 in the highest dose group. As the effects were only observed under extreme conditions (continuous breeding) in the highest dose group at a dose which is irrelevant under normal use conditions and far (about ten times) above the limit dose usually used for such kind of studies these data are regarded as irrelevant with respect to a possible classification. This conclusion is supported by the data on reproductive toxicity available for the structurally closely related 1,2- and 1,4 -butylene glycol for which there is also no evidence of adverse effects on fertility (see read-across document in section 13) as well as by data from additional studies on fertility of 1,3 -butylene glycol, which did not observe adverse effects on fertility at comparable dose levels. Therefore, it is concluded that no classification of 1,3 -butylene glycol for effects on fertility is required.
No teratogenic effects were observed in the presence of 1,3-butylene glycol. Fetotoxic effects in the presence of 1,3-butylene glycol were decreased birthweights (NOAEL 4236 mg/kg bw/d), or missing or incomplete ossificated sternebrae (NOAEL 2500 mg/kg bw/d).
Conducted as part of reproduction study; no definitive dose-related teratological findings in either soft or skeletal tissue. Fetotoxicity(e.g., delayed ossification of sternebrae) noted at 10% and 24% doses, 5000 and 12000 mg/kg bw/d, respectively.
Incidence of fetal skeletal abnormalities in F3B generation:
*: significantly different from respective control, p </= 0.025
**: significantly different from respective control, p </= 0.01
Resorption and implantation data for F3B generation:
Teratogenic effects of 1,3-butylene glycol were investigated as part of a multigeneration study in rats receiving 0, 5, 10 and 24% 1,3-butylene glycol in the diet (0, 2500, 5000, 12000 mg/kg bw/d). No conclusive teratogenic effects were seen in pups of the F3B generation at levels up to 12000 mg/kg bw/d 1,3-butylene glycol in the diet. Incomplete sternebral ossification at mid- and high-dose levels and missing sternebrae at high-dose level were noted, probably indicating slight delayed development of fetal skeletal tissue. The NOAEL for fetotoxicity was 2500 mg/kg bw/d of 1,3-butylene glycol in the diet (Hess et al., 1981).
No teratogenic effects were observed in two studies on developmental toxicity. In a nearly guideline conform test a NOAEL for fetotoxic effects (decreased birthweight) of 4236 mg/kg bw/d was observed (Mankes et al., 1986). Additionally, in this study a number of minor, growth-related structural variations were observed in pups, which were in accordance with the findings of the key study. In the study which was selected as key study (Hess et al., 1981) fetotoxic effects (missing sternebrae, incomplete ossification of sternebrae) were recorded at concentrations of 10% and 24% 1,3-butylene glycol in the diet (5000 and 12000 mg/kg bw/d). The NOAEL was 5% 1,3 -butylene glycol in the diet (2500 mg/kg bw/d).
The effects observed in fetuses, especially the effects on sternebrae, are regarded as substance related and adverse. However, as these effects were only observed at doses which clearly exceed the limit values recommended in current guidelines and as no such effects were observed in investigations with the structural closely related compounds 1,2- and 1,4 -butylene glycol they are not regarded as relevant for classification. Therefore it is concluded that no classification for effects on development is required for 1,3 -butylene glycol.
In the absence of information on species specific effects or metabolism the results are regarded as relevant for humans.
Based on the available data it is concluded that 1,3 -butylene glycol has not to be classified for toxicity on reproduction according to Regulation (EC) No 1272/2008.
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