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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

There is no data available on repeated dose toxicity of "Reaction mass of butane and butene". An assessment of the data for each of the single components Butene, 2 -methylpropene, butane, isobutane and 1,3 -butadiene which are present in "Reaction mass of butane and butene" leads to the conclusion that there is no requirement for classification and labeling after repeated exposure.

Key value for chemical safety assessment

Additional information

There is no data available on repeated dose toxicity of "Reaction mass of butane and butene". Below we present an assessment of the data for each of the single components Butene, 2 -methylpropene, butane, isobutane and 1,3 -butadiene which are present in "Reaction mass of butane and butene".

Butene/2-methylpropene:

 

Repeat dosing studies via inhalation exposure are available for but-1-ene, 2-butene and 2-methylpropene. All studies have shown minimal systemic or target organ toxicity. Exposure of rats to but-1-ene at concentrations of 500, 2000, 8000 ppm (1147, 4589, 18,359 mg/m3) did not induce systemic toxicity in males or females exposed for a minimum of 28 days or in pregnant female rats exposed for 14 days pre-mating, through mating and gestation to day 19. No treatment-related effects on body weight, clinical chemistry, organ weights or histopathology were found. Neurotoxicity screening also showed no effects on motor activity or functional observation battery. A NOAEC of 8000 ppm (18,359 mg/m3) (the highest dose level) was established (Huntingdon, 2003). 

 

Exposure of rats to 2-butene at target concentrations of 2500 or 5000 ppm (5737 or 11,474 mg/m3) did not induce significant systemic toxicity in males and females exposed for 28 days, or in pregnant female rats exposed for 14 days pre-mating, through mating and gestation to day 19 (TNO 1992b). Mean absolute organ weights and relative weights were comparable in all groups. No abnormal, treatment-related macroscopic changes (all groups) or pathological changes (only determined in control and 5000 ppm groups) were observed. The only treatment-related changes were some small decreases in body weights and body weight gains in both sexes at both dose levels and decreased food consumption at 5000 ppm during the first week (premating). Although the authors (TNO 1992b) interpreted the NOAEC as 2500 ppm based on these findings, a reanalysis by RIVM (2007) concluded that as these effects were not dose-related and not consistently present during the study the NOAEC for 2-butene should be 5000 ppm (11,474 mg/m3) (RIVM 2007 and ammended SIDS report 2007).

 

2-Methylpropene also caused no toxicologically significant changes when rats were exposed to 250, 1000 or 8000ppm (573, 2294 or 18,359 mg/m3) for 13 weeks. The only clinical change was an elevation in ketone bodies detected in urine at 1000 ppm and 8000 ppm (males), the toxicological significance of this is unknown. The NOAEC was 8000 ppm (18,359 mg/m3) the highest concentration level tested (1982). Similar results were obtained in 14 week inhalation studies conducted by the NTP (NTP, 1998). F344/N rats and B6C3F1 mice were exposed to 2-methylpropene at concentrations of 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm, (1147, 2294, 4589, 9179, 18,359 mg/m3) for 14 weeks. There were no significant exposure-related toxicologic effects in either species at any dose level. Increased kidney weights in mice; and increased liver and kidney weights and minimal hypertrophy of goblet cells lining the nasopharyngeal ducts in rats, were considered to be non-toxic adaptive responses. The NOAEL for both studies was 8000 ppm (18,359 mg/m3) the highest concentration level tested.

 

Carcinogenicity studies on 2-methylpropene were also conducted by the NTP. F344/N rats and B6C3F1 mice were exposed to 2-methylpropene at concentrations of 0, 500, 2,000 or 8,000 ppm, (1147, 4589, 18,359 mg/m3) for 105 weeks (NTP, 1998). The non-neoplastic findings from these studies were confined to effects on nasal tissues. In mice, hyaline degeneration of the olfactory and respiratory epithelium was increased in both sexes. The severities of hyaline degeneration increased with increasing exposure concentration. However, this was considered by the NTP to be a nonspecific adaptive response that had no adverse effect on affected animals. The NOAEC for toxicity in mice was therefore 8000ppm (18,359 mg/m3). Similar findings were observed in rats although the lesions were more severe. An additional finding in rats was that hypertrophy of goblet cells lining the nasopharyngeal duct was marginally increased with 100% incidence in males at 8000 ppm. The NOAEC for toxicity in the rat study was therefore 2000 ppm (4589 mg/m3), lower than that in mice (OECD SIDS Report for Isobutylene, 2003).

There are no repeat dose toxicity data in humans.

In conclusion, all members of the butenes category showed low sub-chronic and chronic toxicity up to concentrations of 2000 ppm (4589 mg/m3). Effects were confined to mild adaptive responses in the nose.

 

Repeat dose toxicity data are available for the C2-C4 alkanes; also data are available on alkane gas mixtures including Liquefied Petroleum Gas, the composition of which is mainly propane and propene.

 

Petroleum Gases are flammable gases at room temperature and therefore exposure via the dermal or oral routes is unlikely and the requirement to test is waived in accordance with REACH Annex XI.

 

Butane/Isobutane:

 

Non-human studies

Methane CAS Number 74-82-8

No quantitative repeat dose toxicity data are available specifically for methane.

 

Ethane CAS Number 74-84-0

No systemic toxicity (i.e., no affect on survival, haematological or clinical chemistry parameters, food consumption, body weight, organ weight, and histopathology) or neurological effects (as measured by clinical observations, functional observational battery, and motor activity) were observed in a 6-week study to modern guidelines and GLP in which ethane was administered to rats by inhalation. The experimentally defined NOAEC is 16,000 ppm (19678 mg/m3), the highest exposure level tested and 50% of the lower explosive limit (HLS 2010).

 

Propane CAS Number 74-98-6

No neurological, haematological, or clinical chemistry effects were observed in a 6-week study to modern guidelines and GLP in which propane was administered to male and female rats by inhalation. There was no effect of treatment on survival and there were no exposure-related systemic effects or effects on body weight, except the 12000 ppm exposed male animals showed an exposure-related 25% decrease in weight gain during the first week of exposures and this difference persisted for the remainder of the 4 weeks of exposure. The lowest observed adverse effect concentration (LOAEC) in this study is 12,000 ppm (equivalent to 21641 mg/m3), the highest exposure level tested and 50% of the lower explosive limit, based on the reduced bodyweight gain in males. The NOAEC is 4,000 ppm or 7214 mg/m3(HLS 2009).

 

Isobutane CAS Number 75-28-5

No systemic toxicity (i.e., no affect on survival, haematological or clinical chemistry parameters, food consumption, body weight, organ weight, and histopathology) or neurological effects (as measured by clinical observations, functional observational battery, and motor activity) were observed in a 6-week study to modern guidelines and GLP in which isobutane was administered to rats by inhalation. The experimentally defined NOAEC is 9,000 ppm (21394 mg/m3), the highest exposure level tested and 50% of the lower explosive limit (HLS 2010).

A 90 day inhalation study on a 50:50 wt% mixture of isobutane:isopentane exposed male and female rats to nominal 1000 and 4500 ppm daily for 13 weeks, with an interim kill after 28 days. There were no deaths and transient clinical signs were considered treatment but were not dose related. There were no treatment related gross lesions or kidney/liver weight changes. The rats were not significantly affected by the exposures and there was no evidence of hydrocarbon-induced nephropathy in either sex at study termination. At the 28 -day interim kill mild, transient treatment-related kidney effects were observed in the male rats, statistically significant at 1000 ppm only, however there was no evidence of a dose response and the effect disappeared by 90 days. The NOAEC for this study was 4458 ppm, the highest dose tested (Aranyi 1986).

 

Butane CAS Number 106-97-8

No systemic toxicity (i.e., no affect on survival, haematological or clinical chemistry parameters, food consumption, body weight, organ weight, and histopathology) or neurological effects (as measured by clinical observations, functional observational battery, and motor activity) were observed in a 6-week study to modern guidelines and GLP in which butane was administered to rats by inhalation. The experimentally defined NOAEC is 9,000 ppm (21394 mg/m3), the highest exposure level tested and 50% of the lower explosive limit (HLS 2008).

A 90 day inhalation study on a 50:50 wt% mixture of n-butane:n-pentane exposed male and female rats to nominal 1000 and 4500 ppm daily for 13 weeks, with an interim kill after 28 days. There were no deaths and transient clinical signs were considered treatment but was not dose related. Statistically significant decreases in body weights of both sexes were observed by test weeks 3 and 4, with the males, but not the females, recovering towards the end of the exposure period. There were no treatment related gross lesions or kidney/liver weight changes. Rats were not significantly affected by the exposures and there was no evidence of hydrocarbon-induced nephropathy in either sex at study termination.

At the 28 -day interim kill, mild, transient treatment-related but not exposure related kidney effects were observed in the male rats, the effect disappeared by 90 days. The NOAEC for this study was 4489 ppm, the highest dose tested (Aranyi 1986).

 

In a mixture study, male rats were exposed by inhalation to concentrations up to 11.8 mg/L (11800 mg/m3 or 4437 ppm) of a mixture containing 25% (by weight) each of isobutane, n-butane, n-pentane, and isopentane for 6 hours per day, 5 days per week, for 3 weeks. There were no signs of systemic toxicity, no effects on bodyweight, organ weights, haematology or serum chemistry and no treatment-related gross or microscopic lesions. The NOAEC for systemic effects and kidney effects is 11.8 mg/L (11800 mg/m3 or 4437 ppm), the highest dose tested (Halder, 1986).

 

Petroleum gases, liquefied

The major constituents are identified as propane and propene (93.5%).

 

The repeated-dose inhalation toxicity of petroleum gas products in laboratory animals was investigated in a 90 day study to modern guidelines and GLP. Groups of rats were exposed to target concentrations of 0; 1,000; 5,000; or 10,000 ppm liquefied petroleum gas (LPG) for 13 weeks (HLS, 2009). The highest exposure concentration was approximated 50% of the lower explosive limit. There was no treatment-related effect on survival, terminal body weight, food consumption, functional observational battery, motor activity parameters, haematological parameters, clinical chemistry values, macroscopic or microscopic evaluations, or on organ weights at any exposure concentration. A no observed adverse effect concentration (NOAEC) of 10,000 ppm is reported for the repeated-dose toxicity of the LPG tested.

 

 

Human studies

Little quantitative data were identified.

In a controlled exposure study, Stewart et al (1977, 1978) exposed adult volunteers to isobutane at 500 ppm (1189 mg/m3) 1, 2 or 8 hours/day, five days/week for 2 weeks. During the investigation, all volunteers were kept under comprehensive medical surveillance which included cardiac and pulmonary responses. Repetitive exposures to isobutane were without any measurable untoward physiological effect.

 

Summary

Simple short chain alkanes (i.e methane, ethane, propane, butane, isobutane) can be considered in a similar manner, inhalation exposure is the most relevant route, and current GLP-compliant guideline study data are available for ethane, propane, butane and isobutane which demonstrate low repeat dose toxicity (up to six weeks in duration). These data are supported by studies up to 90 days in duration on C4-C5 mixtures and a 90 day study on liquefied petroleum gas (LPG, main constituent propane and propene), which gave a no observed adverse effect level (NOAEC) of 10,000 ppm, the maximum dose level tested.

 

1,3-Butadiene:

 

The repeat dose toxicity of 1,3-butadiene has been extensively reviewed, including an EU Risk Assessment Report (2002), ECETOC (1997), US EPA (2002) and TCEQ (2008). This endpoint summary is based on the EU RAR (2002) and there have been no new reports on the chronic toxicity of 1,3-butadiene since 2002. The studies described here and for which robust summaries have been prepared are the most significant and reliable studies on 1,3-butadiene although other less reliable studies are described in EU RAR (2002).  

Non-Human Information 

In the rat, exposure to 1,3-butadiene results in low toxicity. The most comprehensive information in the rat is available from a carcinogenicity study (Owen et al, 1987). In this key study, male and female rats were exposed to 1,3-butadiene at 0, 1000, or 8000 ppm (2212 and 17701 mg/m3), 5 days/week, for up to 2 years. There were no effects on haematology, blood chemistry, urine analysis and neuromuscular function that were associated with treatment. Non-neoplastic findings were limited to changes in clinical condition, suppression of body weight gain, reduced survival, increased weights of liver, kidney, heart, lung and spleen, nephrosis of the kidney and focal metaplasia in lung. The neoplastic changes are described in the Section on Carcinogenicity. A NOAEC of 1000 ppm (2212 mg/m3) for systemic toxicity was established based on some minimal toxic effects (increased heart weight and kidney nephrosis) occurring at 8000 ppm.  

In other studies in rats, inhalation exposure of rats to 1,3-butadiene at concentrations of 1000, 2000, 4000 and 8000 (2212, 4425, 8850 and 17701 mg/m3) for 13 weeks produced no treatment-related effects except moderately increased salivation. There were no effects on growth rate, food consumption, haematology, clinical chemistry, urine analysis or macroscopic and histopathological effects. In this study the NOAEC for 1,3-butadiene in the rat was 8,000 ppm (17,701 mg/m3) (Crouch et al 1979). Similar results were reported by Bevan et al (1996), where rats were exposed to 1,3-butadiene at a single concentration of 1000 ppm (2212 mg/m3) for 13 weeks. There were no effects other than minor increases in liver and kidney weights in male rats. Hyaline droplet formation was observed in the kidneys of 20% of treated rats but there was no cytotoxicity associated with this. None of the effects were considered to be adverse.  

Other species were investigated by Carpenter et al (1944) and no significant adverse effects were noted. Rats, guinea pigs, rabbits and dogs were exposed to 1,3-butadiene at concentrations of 600, 2300, and 6700 ppm (1327, 5089 and 14824 mg/m3), 7.5h/day, 6 days/week for 8 months. There were no deaths and no effects on body weight, organ weights, urinalyses, micropathology, clinical chemistry or haematology although the numbers of animals were small. At the highest concentration of 6700 ppm (14824 mg/m3) body weight gain was reduced in rats and there was a light cloudy swelling in some livers of rats and rabbits.

Repeated exposure of mice to 1,3-butadiene results in toxicity. The non-neoplastic data from two carcinogenicity studies are available (NTP 1984 and NTP 1993) although poor survival and severe systemic toxicity at concentrations at and above 20 ppm (44 mg/m3) confounds interpretation of these studies. In the first study (NTP, 1984), male and female B6C3F1 mice were exposed to 1,3-butadiene for 2, 14 or 60 weeks at concentrations of 0, 625, 1250, 2500, 5000 and 8000 ppm (1382, 2765, 5531 and 17701 mg/m3), 6 hours/ day, 5 days/ week. Survival was unaffected and no pathologic effects were observed after 2 weeks. After 14 weeks, the survival of male mice exposed to 5,000 or 8,000 ppm 1,3-butadiene was markedly reduced and body weight gain was reduced at 2500 ppm and above. No other compound-related effects were observed at this time and a NOAEC of 1250 ppm (2765 mg/m3) can be established, based on reductions in body weight gain at the higher dose level. After 60 weeks, there wasclear evidenceof carcinogenicity, as shown by increased incidences of tumours at many sites in both sexes. Exposure of mice to 1,3-butadiene was primarily associated with tumours of the haematopoietic system. Non-neoplastic effects seen were ovarian and testicular atrophy, congestion, haemorrhage and hyperplasia of the lungs, haemorrhage and necrosis of the liver, thymus and bone marrow atrophy, epithelial hyperplasia of the forestomach and endothelial hyperplasia and mineralisation of the heart. Chronic inflammation and fibrosis developed in the nasal cavities of males. 1,3 -Butadiene therefore caused severe toxicity and survival was reduced due to malignant tumours. A NOAEL could not be identified in this study.

In the second study (NTP, 1993) mice were exposed to 6.25, 20, 62.5, 200 or 625 ppm 1,3-butadiene (13, 44, 138, 442 or 1382 mg/m3), 6 hours/ day, 5 days/ week for up to 2 years. This study is the key study for the repeat dose toxicity of 1,3-butadiene in the mouse due to its length and number of exposure concentrations. Survival was reduced at 20 ppm and above due to malignant neoplasms. Increased incidences of non-neoplastic lesions in exposed mice included bone marrow atrophy; testicular atrophy; ovarian atrophy, angiectasis, germinal epithelial hyperplasia, and granulosa cell hyperplasia; uterine atrophy; cardiac endothelial hyperplasia and mineralization; alveolar epithelial hyperplasia; forestomach epithelial hyperplasia; and Harderian gland hyperplasia. Ovarian atrophy was observed at all dose levels after 2 years. The exposure response relationship for ovarian atrophy is unclear as although it developed during the study with NOAECs of 62.5 ppm after 9 months and 6.25 ppm after 15 months, its appearance in the lowest dose group coincided with general senescence of the reproductive system. Tumours also arose at all exposure levels and survival was markedly reduced. The EU RAR (2002) states “it is possible that the gonadal effects seen in this study are a secondary consequence of severe generalised toxicity”. No NOAEC could be defined for this study.

Other supporting studies also demonstrated that 1,3-butadiene is toxic to mice in studies from 2-13 weeks duration (NTP 1984, Bevan et al 1996). The bone marrow, ovary and testis are important targets. Bevan et al (1996) exposed male and female mice to 1,3-butadiene at 1000 ppm (2,212 mg/m3), 6 hr/day, 5 days/wk for 13 weeks, treatment-related ovarian atrophy, mild macrocytic anaemia and slight testicular degeneration occurred.

Irons et al (1986a,b) investigated the effect of 1,3-butadiene on haematological parameters in mice. Male B6C3F1 mice were exposed to 1,3-butadiene at 1250 ppm (2765 mg/m3), 6 hr/day, 6 days/week for 3 to 24 weeks. Treatment resulted in macrocytic-megaloblastic anaemia, including a decrease in circulating erythrocytes, total haemoglobin, and haematocrit and an increase in mean corpuscular volume. Analysis of bone marrow cells showed they had increased numbers of cells in S phase. These findings indicated the bone marrow to be an important target organ for 1,3-butadiene toxicity (Irons et al,1986a). In a further study, the potential effect of murine leukemia retroviruses on 1,3-butadiene-induced anaemia was investigated (Irons et al, 1986b). Male NIH Swiss mice were exposed to 1,3-butadiene at 1250 ppm (2765 mg/m3), 6 hr/day, 6 days/week for 6 weeks. NIH Swiss mice do not possess intact endogenous ecotropic type C murine leukemia retroviruses which may have played a role in 1,3-butadiene- induced anaemia in other mouse strains. Treatment resulted in macrocytic-megaloblastic anaemia and an 8-fold increase in circulating micronuclei. These findings confirmed that the bone marrow is an important target for 1,3-butadiene toxicity in mice that is independent of murine leukemia retrovirus background and expression.  

The effect of 1,3-butadiene on immune function in mice was investigated by Thurmond et al (1986).Exposure of mice to 1250 ppm (2766 mg/m3) 1,3-butadiene by inhalation 6 hr/ day, 5 days/ week, for 6 or 12 weeks caused some minor changes in immune function but there were no detectable toxicologically significant persistent immunological effects.

Human Information 

There is limited useful information on the (non-neoplastic) health effects of repeated exposure to 1,3-butadiene in humans, data prior to 2002 are summarised in the EU RAR (2002). One limited study (Cowles et al, 1994) showed no significant differences in health status or haematology parameters in workers exposed to 1,3-butadiene at a mean 8 h time weighted average of about 3.5 ppm (7.74 mg/m3) compared with a non-exposed group, even in a sub-group where the highest 1,3-butadiene exposure (8 h time weighted average) was about 10 ppm (22.1 mg/m3). A more recent study (Tsai et al, 2003) also showed no evidence of adverse haematological findings associated with exposure to 1,3-butadiene when workers from 2 plants were compared with a non-1,3-butadiene exposed group. Haematological parameters were compared in workers at two 1,3-butadiene plants who had participated in the Shell Butadiene Medical Surveillance Program from 1979 -2003 with a group of employees who had not participated in the program and therefore were not exposed to 1,3-butadiene (although they may been exposed to other chemicals). Exposure data showed that the 1,3-butadiene surveillance group for 1979-1996 had a mean overall exposure of 4.55 ppm (10.07 mg/m3)(8h, 10h and 12h-time weighted average); from 1997, this figure was 0.25 ppm (0.55 mg/m3). Before 1996 the OSHA exposure limit was 1000 ppm and post-1996 it was 1 ppm. Both facilities gave similar exposure results. There were no significant differences in 6 Complete Blood Count parameters (white blood cell count, lymphocyte count, red blood cell count, hemoglobin concentration, mean corpuscular volume, and platelet count) between the 1,3-butadiene surveillance group compared with the comparison group when compared on an individual plant basis or all results combined.

Long-term exposure of humans to 1,3-butadiene may result in an increased risk of lymphohaematopoietic cancer. Studies of the causes of mortality of workers exposed to 1,3-butadiene have shown no increases in mortality due to lung cancer, cardiovascular disease and digestive system cancer indicating that 1,3-butadiene has no chronic effects on these organ systems in humans (Divine and Hartman 2001, Delzell et al 2006).

Long-term exposure of humans to 1,3-butadiene may result in lymphohaematopoietic cancer. Studies of the causes of mortality of workers exposed to 1,3-butadiene have shown no increases in mortality due to lung cancer, cardiovascular disease and digestive system cancer indicating that 1,3-butadiene has no chronic effects on these organ systems in humans (Divine and Hartman 2001, Delzell et al 2006).

Conclusions 

1,3-Butadiene has low toxicity in the rat, with minimal effects seen after exposure to 8000 ppm (17701 mg/m3) for 2 years. Limited data suggests that 1,3-butadiene also has low toxicity in guinea pigs, rabbits and dogs. No chronic non-neoplastic effects were seen in humans either, although data is also limited. 1,3-Butadiene exhibits marked species differences in repeat dose toxicity via inhalation exposure. The mouse is the most sensitive species where the target organs are bone marrow, ovary and testis. The effects on the bone marrow are consistent with the development of tumours of the haematopoietic system in carcinogenicity tests (NTP 1984, 1993), whilst there is no clear evidence of effects on immune function.  

Although ovarian atrophy has been observed in mice exposed to 1,3-butadiene at concentrations as low as 6.25 ppm (13 mg/m3) severe generalised toxicity occurred in this study. The conclusion of the EU RAR (2002) was that “no useful information on the dose-response relationship for non-neoplastic effects can be derived from the available long-term studies in this species, as tumour formation and tumour-related mortality dominated the response at all exposure levels in these studies (6.25 ppm and above). The only useful information in relation to repeated dose toxicity in the mouse comes from short-term repeated exposure studies.” Ovarian toxicity in mice was also reported in the 13 week study of Bevan et al (1996). It is noteworthy that the EU RAR (2002) omitted this study and therefore it was not included in its review and discussion on the dose-response relationship for ovarian toxicity but it is clear from this study that ovarian toxicity occurred at 1000 ppm in the absence of systemic toxicity. Mice are particularly sensitive to 1,3-butadiene-induced toxicity and there is evidence to indicate that ovarian atrophy is caused by the diepoxide metabolite of 1,3-butadiene (Doerr et al, 1996) which is produced in mice. Quantitative differences in the metabolism of 1,3-butadiene in rats and mice in the production and elimination of the epoxide metabolites (Swenberg et al, 2007) are believed to be responsible for the marked species difference in toxicity (see Section on, Toxicokinetics, Metabolism and Distribution). It is noteable that ovarian atrophy is not observed in rats. The available data indicate that humans are similar to rats in that they do not readily produce the diepoxide. 

The NOAEC for repeat dose toxicity is therefore 1000 ppm (2212 mg/m3) as defined by the study of Owen et al (1987) in the rat.    

Additional References 

Doerr, JK, EA Hollis, and IG Sipes. (1996). Species difference in the ovarian toxicity of 1,3-butadiene epoxides in B6C3F1 mice and Sprague-Dawley rats. Toxicology 113:128-36.  

ECETOC (1997). 1,3-Butadiene OEL Criteria document. Special Report No. 12  

EU RAR (2002). European Union Risk Assessment Report for 1,3-butadiene. Vol. 20. European Chemicals Bureau (http: //ecb. jrc. ec. europa. eu/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/butadienereport019. pdf)

Swenberg JA, Boysen G, Georgieva N, Bird MG, Lewis RJ. (2007). Future directions in butadiene risk assessment and the role of cross-species internal dosimetry. Chem Biol Interact. 166: 78-83.  

TexasCommission on Environmental Quality (TCEQ) (2008). Development Support Document. 1,3-Butadiene. Chief Engineer’s Office. Available: http: //tceq. com/assets/public/implementation/tox/dsd/final/butadiene, _1-3-_106-99-0_final. pdf

United States Environmental Protection Agency (USEPA). (2002). Health Assessment of 1,3-Butadiene. EPA/600/P-98/001F.for Environmental Assessment, Office of Research and Development,D. C.

Justification for classification or non-classification

There is no data available on repeated dose toxicity of "Reaction mass of butane and butene". An assessment of the data for each of the single components Butene, 2 -methylpropene, butane, isobutane and 1,3 -butadiene which are present in "Reaction mass of butane, and butene" leads to the conclusion that there is no requirement for classification and labeling after repeated exposure according to CLP (GHS) or 67/548/EEC.