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EC number: 209-674-2
CAS number: 590-19-2
No further studies.
are no reproduction studies carried out on 1,2-butadiene itself,
however, in accordance with the strategy described in Section 7.1
(Toxicokinetics endpoint summary), reproduction studies in the rat on
the structural analogue, 1,3-butadiene, are used for read across and
reproduction studies in the mouse and rat on the mono-butene isomers,
1-butene, 2-butene and 2-methylpropene are also used to provide weight
of evidence. There is no
requirement for a 2 -generation reproduction study as the registration
intention under REACH for this substance is between 100-1000 tonnes.
key reproduction/developmental screening study (OECD Guideline 421
study) on buta-1,3-diene has been carried out in rats (WIL, 2003). Male
and female rats were exposed to 1,3-butadiene at target concentrations
of 300, 1500 or 6000 ppm (663, 3319 or 13,276 mg/m3) for two
weeks prior to mating, during mating and through gestation and
lactation. F1 males and females were exposed for 7 days post weaning
(pnd 21-27 or 28-34). Signs
of toxicity were seen in males and females exposed to 1500 or 6000 ppm
but there were no treatment-related effects on gonadal function, mating
behaviour, conception, gestation, parturition or lactation. Furthermore,
there were no treatment-related effects on the growth or development of
the offspring during lactation through to weaning. Reduced
body weights of the offspring were observed only following post-weaning
exposure to 1500 or 6000 ppm. The NOAEC for reproductive toxicity was
6000 ppm (13,276 mg/m3) (the highest concentration tested.
supporting reproduction toxicity studies (OECD Guideline 422 studies)
have been carried out on mono-butene isomers. Inhalation exposure of
rats to but-1-ene and 2-butene produced no effects on reproductive
toxicity including fertility. Male and female rats were exposed to the
butene isomers for two weeks prior to breeding, during breeding and
until day 19 of gestation. The dams were then allowed to deliver their
litters, which were retained until post-natal day 4. Target
concentrations were: but-1-ene
500, 2000 or 8000 ppm (1147, 4589, 18,359 mg/m3) and 2-butene
2500 or 5000 ppm (5737 or 11,474 mg/m3). There was no
evidence of systemic toxicity for but-1-ene in the parents. Slight
reductions in maternal body weight occurred with 2-butene. There were no
effects on mating behaviour, fertility and gestation indices, the number
of implantation sites per dam, numbers of pups delivered, viability of
pups at and after birth and the pup sex ratio when compared to the
control group (Huntingdon 2003, TNO 1992b). Based on these data, the
NOAECs for reproductive toxicity were 8000 ppm (18,359 mg/m3)
for but-1-ene and 5000 ppm (11,474 mg/m3), for 2-butene, the
highest concentrations tested.
addition, no effects on male and female reproductive parameters in rats
and mice were observed in 14 week inhalation exposure studies of the
mono-butene isomer, 2-methylpropene. These repeat dosing studies
included parameters such as sperm analysis, oestrus cycle analysis and
histopathology (although mating was not carried out). NOAECs of 8000 ppm
(18,359 mg/m3) for both rat and mouse studies were established (NTP
are no data on the effect of 1,2-butadiene on fertility in humans.
conclusion, the weight of evidence from 1,3-butadiene and mono-butene
isomers indicates that 1,2-butadiene has low potential for reproductive
toxicity, including fertility. The NOAEC for fertility is 6000 ppm
(13,276 mg/m3), based on the key study for on 1,3-butadiene (WIL 2003).
There are no developmental toxicity studies carried out on 1,2-butadiene itself but a weight of evidence evaluation of developmental toxicity studies with 1,3-butadiene and the mono-butene isomer, 2-methylpropene, indicates that 1,2-butadiene has low potential for developmental toxicity. There was no evidence of developmental toxicity at the lower exposure levels where maternal toxicity was not encountered. The NOAEC for developmental toxicity is 1000 ppm (2212 mg/m3), based on two key studies on 1,3-butadiene.
are no developmental toxicity studies carried out on 1,2-butadiene
itself, however, in accordance with the strategy described in Section
7.1 (Toxicokinetics endpoint summary), two key developmental toxicity
studies in the rat on the structural isomer, 1,3-butadiene, are used for
read across and a supporting developmental toxicity study in the rat on
the mono-butene isomer, 2-methylpropene, has been used to provide weight
a study conducted by the NTP, rats were exposed to 1,3-butadiene from
days 6-15 of gestation at concentrations of 40, 200 or 1000 ppm (88,
442, 2212 mg/m3) (Hackett 1987a). The NOAEC for maternal
toxicity was 200 ppm (442 mg/m3) based on reduced body
weights. Exposure to 1,3 -butadiene had no effects on developmental
parameters at any dose and the NOAEL for developmental toxicity in the
rat was 1000 ppm (2212 mg/m3). In a study conducted by HLE
(1984) pregnant rats were exposed to 1,3 -butadiene (200, 1000 and 8000
ppm; 442, 2212 and 17701 mg/m3) from days 6-15 of gestation.
Maternal toxicity occurred at all dose levels tested. At 8000 ppm,
increased incidences of major foetal defects occurred such as severe
wavy ribs. These effects were considered to be indicative of delayed
development associated with maternal toxicity. There was no evidence of
teratogenicity at the lower exposure levels where maternal toxicity was
not encountered. The NOAEC for teratogenicity was 1000 ppm (2212 mg/m3).
(isobutylene) has been tested in a rat developmental toxicity study
(OECD Guideline 414) by inhalational exposure at levels of 500, 2000 and
8000 ppm (1147, 4589, 18,359 mg/m3). 2-Methylpropene had no
effect on the number, growth or survival of the foetuses in utero and no
effect on foetal development (determined by visceral and skeletal
analysis). A NOAEC of 8000 ppm (18,359 mg/m3) was established
(CTL 2002). The low developmental toxicity of 2-methylpropene is
consistent with that of other members of the butene category. 2-Butene
and 1-butene also had no effect on developmental toxicity when tested in
OECD Guideline 422 studies by inhalation exposure. Neither of these
compounds produced treatment-related effects on the development of pups
during the reproductive toxicity element of the studies. There were no
effects on pup body weight gain or observed during macroscopic
examination of pups at post mortem (Huntingdon 2003, TNO 1992). The
NOAECs for developmental toxicity were 8000 ppm (18,359 mg/m3) for
1-butene and 5000ppm (11,474 mg/m3) for 2-butene (the highest
are no data on the effect of 1,2-butadiene on developmental toxicity in
conclusion, the weight of evidence from 1,3-butadiene and
2-methylpropene indicates that 1,2-butadiene has low potential for
developmental toxicity. The NOAEC for developmental toxicity is 1000 ppm
(2212 mg/m3), based on the key studies of Hackett (1987) and
HLE (1981) on 1,3-butadiene.
-Butadiene is not toxic to reproduction and has no effect on fertility
or development. Consequently, it does not warrant classification under
Dir 67/548/EEC or GHS/CLP.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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