Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
There are no further data on members of the butene category.
Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
18 359 mg/m³
Additional information

There are no 2-generation reproduction studies available on members of the butenes category but there is sufficient weight of evidence from reproductive toxicity studies and reproductive endpoints in repeat dosing studies to conclude that the potential for effects on fertility is low and therefore further testing is scientifically unjustified (Annex XI adaptation).

 

Reproduction toxicity studies (OECD Guideline 422 studies) via inhalation exposure are available for but-1-ene (Huntingdon, 2003) and 2-butene (TNO 1992b). 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, 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 but these were inconsistent and no other treatment-related changes occurred. 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.

 

In addition, no effects on male and female reproductive parameters in rats and mice were observed in 14 week inhalation exposure studies of 2-methylpropene. These repeat dosing studies included parameters such as sperm analysis, estrus 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 1998).

 

There are no studies on the effects of the butenes on fertility in humans.

 

In conclusion, the weight of evidence from members of the butenes category indicates that they are not toxic to reproduction, including fertility. The NOAEC of 8000 ppm (18,359 mg/m3) for fertility is based on the NOAEC for but-1-ene in the reproductive study (Huntingdon 2003).



Short description of key information:
A weight of evidence evaluation of reproductive toxicity studies and reproductive endpoints in repeat dosing studies with members of the butenes category indicates that they are not toxic to reproduction, including fertility. No treatment-related reproductive toxicity or effects on reproductive endpoints in repeat dosing studies were observed in rats or mice after inhalational exposure to category members.

Effects on developmental toxicity

Description of key information
Members of the butenes category are not toxic to development. A developmental toxicity study conducted in rats on 2-methylpropene with inhalational exposure produced no treatment-related developmental toxicity. In addition, a weight of evidence evaluation of reproductive toxicity studies indicates that other members of the butenes category are not developmental toxins.
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
18 359 mg/m³
Additional information

Members of the butenes category are not toxic to development. 2-Methylpropene has been tested in a key rat developmental toxicity study (OECD Guideline 414) by inhalational exposure at concentrations of 500, 2000 and 8000 ppm (1147, 4589, 18,359 mg/m3). 2-Methylpropene had no effect on the females during gestation. There were also no effects on the number, growth or survival of the foetuses in utero and no effects on foetal development (determined by visceral and skeletal analysis). A NOAEC of 8000 ppm (18,359 mg/m3) (the highest concentration tested) was established for maternal toxicity and foetal toxicity (CTL 2002).

 

The low developmental toxicity of 2-methylpropene is consistent with that of other members of the butene category. 2-Butene and but-1-ene also had no effect on developmental toxicity when tested in OECD Guideline 422 studies by inhalation exposure. Neither of these isomers 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 1992b). The NOAECs for developmental toxicity were 8000 ppm (18,359 mg/m3) for but-1-ene and 5000ppm (11,474 mg/m3) for 2-butene (the highest concentrations tested).

 

There are no data on the developmental toxicity of the butenes in humans.

 

In conclusion, the weight of evidence from members of the butenes category indicates that they are not developmental toxins. The NOAEC of 8000 ppm (18,359 mg/m3) for developmental toxicity is based on the NOAEC for 2-methylpropene in the developmental toxicity study (CTL 2002). 

Toxicity to reproduction: other studies

Additional information

There are no other studies, in addition to those described above, on the reproductive or developmental toxicity of members of the butene category.

Justification for classification or non-classification

 Members of the butenes category are not toxic to reproduction and have no effect on fertility or development. Consequently category members do not warrant classification under Dir 67/548/EEC or GHS/CLP.