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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
DNEL derivation method:
other: OEL, based on German TRGS 900
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General


DNEL/DMEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).


Inhalation


Long term, systemic DMEL – exposure via inhalation (worker)


After chronic exposure to test item vapours in rats, tumours were obtained at the port of entry (nose and lung). The substance is harmonized classified for carcinogenicity Cat.2. Based on these observations from the carcinogenicity study in rats, the DMEL is labelled as a local DMEL which is considered to be protective also from systemic effects. Therefore, no DMEL for systemic effects was derived.


Acute, systemic DNEL/DMEL- exposure via inhalation (worker)


The substance is classified for acute inhalation toxicity Cat.4 (H332) according to Regulation (EC) No 1272/2008 (CLP Regulation). The substance did not cause mortality or clinical signs at a concentration of 6.3 mg/L air in the acute inhalation toxicity study reported by BASF AG (1978). This concentration is much higher than the NOAEC of 0.6 mg/L (200 ppm) for systemic/local effects after chronic inhalation of the substance in rats (NTP, 1988). Thus, effects after long term exposure are more relevant and the DMEL for long term exposure is considered to ensure a sufficient level of protection for acute/short term inhalative exposure. Therefore, no DNELs/DMELs are proposed for acute systemic exposure.


Long term, local DMEL- exposure via inhalation (worker)


Butylene oxide has caused nasal and lung tumours in rats after 2 years inhalation exposure. This indicates that Butylene oxide is a carcinogen, at least at high concentrations at the port of entry, most likely due to its irritative potential. The substance is harmonized classified for carcinogenicity Cat.2. Inhalation appears to be the most important route of exposure and the results provide a basis for a quantitative estimation of the risk of exposure. The DMEL is based on the local tumours obtained at the port of entry. It is further proposed that the DMEL derived for these local tumours provides also sufficient protection from any systemic effects as hardly any systemic toxicity is noted in repeated dose studies.


The following tumour incidences were obtained in male rats (Study report NTP TR 329, 1988, page 46:


























 Dose



 Nasal adenoma



 Lung adenoma plus carcinoma



 0 ppm



 0



 0



 200 ppm



 0



 8.9%



 400 ppm



 24.2%



 17.6%



The DMEL of 1 ppm is based on the German TRGS 900 OEL.


At 400 ppm there was a markedly decreased survival in male rats. In females, a low tumor response was seen only at 400 ppm. For the nasal tumors in males a T25 of 413 ppm is obtained. For lung tumors in males a T25 of 568 ppm (calculated from the top dose) or 562 ppm (calculated from the lower dose) is obtained. A linear extrapolation from a T25 of 500 ppm as a point of departure would indicate a numerical risk of 1:2000 at 1 ppm. However, the real risk is assumed to be magnitudes lower due to a likelyhood for non-linear elements in the dose response relation at lower doses (as has been shown for propylene oxide). 1 ppm (= 3 mg/m3) can therefore serve as a preliminary DMEL for butylene oxide.


Short term, local DNEL- exposure via inhalation (worker)


The substance is harmonized classified for STOT SE 3 (H335), skin and eye irritation (Cat.2) according to Annex VI of Regulation (EC) No 1272/2008. Therefore, a qualitative risk characterization should be performed for this endpoint. This qualitative approach has to be implemented to deal with irritative properties for the respiratory tract after inhalation. As a result, a medium hazard is derived. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent mucous membrane exposure.


Dermal


Long term, systemic DNEL- dermal exposure (worker)


No repeated dose dermal toxicity study with the substance is available. On the other hand, skin exposure does not appear to be a common route of exposure and the high vapour pressure and volatility of the material and its irritating properties indicate that dermal exposure will be minimal. Therefore, no DNELs/DMELs were derived for systemic dermal exposure and a qualitative approach is implemented to deal with the irritative properties of the substance. As a result, a medium hazard is derived.


Further, the long term acute inhalative DMEL is based on the local tumours obtained at the port of entry. It is further proposed that this DMEL derived for these local tumours provides also sufficient protection from any systemic effects.


 


Acute, systemic DNEL- dermal exposure (worker)


An acute dermal toxicity hazard leading to C&L has been identified for the substance (Cat 4, H312). However, the skin exposure is considered minimal due to high vapor pressure and volatility of the substance. Therefore, no DNEL was derived and a qualitative approach is implemented to deal with the irritative properties of the substance. As a result, a medium hazard is derived.


Long term & acute, local DNEL- dermal exposure (worker)


According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterization, a qualitative risk characterization should be performed for this endpoint. This qualitative approach has to be implemented to deal with the irritative properties of the substance. As a result, a medium hazard is derived. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent skin, eye and mucous membrane exposure.


Hazard to the eye-local effects (worker)


The test item is classified for eye irritation Cat 2 (H319) under Regulation (EC) No 1272/2008. Thus, a qualitative risk assessment is done and the substance is assigned to the low hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016). Suitable eye protection should be worn when handling the substance.


References


ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:


Characterisation of dose [concentration]-response for human health. Version 2.1, November 2012


ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

No DNEL/DMEL is proposed for the general population, since the material is not foreseen in consumer products.