4-(vinyloxy)butan-1-ol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.35 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.1 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

General Remarks

4-(vinyloxy)butan-1-ol (HBVE) is practically exclusively used as an industrial intermediate for the manufacture of vinyl ether polymers and co-polymers. During manufacture and processing of HBVE, worker exposure is controlled by the use of closed systems, industrial hygiene controls, and personal protective equipment. The substance is manufactured and used under strictly controlled conditions over the entire lifecycle. Exposure is limited to occasional sampling tasks for quality control. Transport, storage tanks, reactors, processing equipment, and feeds operate in fully closed systems.

Short term exposure worker (systemic effects)

 

It is not possible to derive a DNEL for acute effects based on the available data. The acute toxicity of HBVE is low with respect to the inhalative and dermal routes of exposure.

 

Short term exposure worker (local effects)

HBVE is in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 classified as eye irritant (cat. 2A). The performed guideline test is not providing dose-response data that could be used for the derivation of a DNEL.

According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent eye exposure.

 

Long term exposure worker (systemic effects)

Inhalatory and dermal

The DNELs for inhalatory and dermal long term exposure are derived from the NOAEL obtained in an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; BASF SE 2010). HBVE was administered orally via gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at doses of 50, 150, and 450 mg/kg body weight/day. The duration of treatment covered a 2-week pre-mating and mating period in both sexes, approximately 1 week postmating in males, and the entire gestation period as well as 4 days of lactation in females. No adverse effects on fertility of the F0 parental animals of both sexes at dose levels of 50, 150 and 450 mg/kg bw/d were observed. The test substance caused also no impairments of the reproductive performance. Mating behaviour, conception, gestation, parturition, as well as sexual organ weights and gross and histopathological findings of these organs were not influenced. Slight general systemic toxicity was noted in the F0 parents at 450 mg/kg bw/d. An additional clinical finding was a decreased body weight gain in high-dose males. Concerning clinical pathology no treatment-related, adverse effects were observed up to a dose of 450 mg/kg bw/d. Regarding pathology there were no substance-related organ weight changes, gross lesions, or microscopic findings. Under the conditions of this study the NOAEL for reproductive performance, fertility and for developmental toxicity is 450 mg/kg body weight/day, the highest dose tested. The NOAEL for general, systemic toxicity of the test substance is 150 mg/kg body weight/day for the F0 parental animals based on adverse clinical findings (males + females) and decreased body weight gain (males) at 450 mg/kg body weight/day.

 

Long term worker (systemic, inhalation)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 150 mg/kg bw (OECD 422; oral; rat)	adverse clinical findings and decreased body weight gain
Step 2) modification of the starting point
	1/0.38	route to route (8h exposure)
	50/100	absorption oral to inhal.
	6.7 m³/10 m³	to light work
Step 3) Assessment factors
Exposure duration	6	subacute to chronic
Interspecies	1	no interspecies extrapolation for inhal.
Intraspecies	3	worker
DNEL	Value
For workers	150 mg/kg x 0.5 x 0.67 / (0.38 x 6 x 1 x 3) = 7.35 mg/m³

 

 

Long term worker (systemic, dermal)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 150 mg/kg bw (OECD 422; oral; rat)	adverse clinical findings and decreased body weight gain
Step 2) modification of the starting point
	1/1	route to route
Step 3) Assessment factors
Exposure duration	6	subacute to chronic
Interspecies	4	extrapolation systemic effects rat to human
Intraspecies	3	worker
DNEL	Value
For workers	150 mg/kg / (6 x 4 x 3) = 2.1 mg/kg bw/d

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.17 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

General Remarks

4-(vinyloxy)butan-1-ol (HBVE) is practically exclusively used as an industrial intermediate for the manufacture of vinyl ether polymers and co-polymers. Consumer exposure to residual HBVE is considered to be negligible, since most of the marketed vinyl ether polymers and co-polymers are heat-treated and potentially existing residual HBVE is expected to evaporate during this process.

Short term exposure general population (systemic effects)

 

Same considerations as for the worker.

 

Short term exposure general population (local effects)

 

Same considerations as for the worker.

 

Long term exposure general population (systemic effects)

Oral, Inhalatory and dermal

The DNELs for oral, inhalatory and dermal long term exposure are derived from the NOAEL obtained in an oral combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; BASF SE 2010). HBVE was administered orally via gavage to groups of 10 male and 10 female Wistar rats (F0 animals) at doses of 50, 150, and 450 mg/kg body weight/day. The duration of treatment covered a 2-week pre-mating and mating period in both sexes, approximately 1 week postmating in males, and the entire gestation period as well as 4 days of lactation in females. No adverse effects on fertility of the F0 parental animals of both sexes at dose levels of 50, 150 and 450 mg/kg bw/d were observed. The test substance caused also no impairments of the reproductive performance. Mating behaviour, conception, gestation, parturition, as well as sexual organ weights and gross and histopathological findings of these organs were not influenced. Slight general systemic toxicity was noted in the F0 parents at 450 mg/kg bw/d. An additional clinical finding was a decreased body weight gain in high-dose males. Concerning clinical pathology no treatment-related, adverse effects were observed up to a dose of 450 mg/kg bw/d. Regarding pathology there were no substance-related organ weight changes, gross lesions, or microscopic findings. Under the conditions of this study the NOAEL for reproductive performance, fertility and for developmental toxicity is 450 mg/kg body weight/day, the highest dose tested. The NOAEL for general, systemic toxicity of the test substance is 150 mg/kg body weight/day for the F0 parental animals based on adverse clinical findings (males + females) and decreased body weight gain (males) at 450 mg/kg body weight/day.

 

Long term general population (oral)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 150 mg/kg bw (OECD 422; oral; rat)	adverse clinical findings and decreased body weight gain
Step 2) Assessment factors
Exposure duration	6	subacute to chronic
Interspecies	4	extrapolation systemic effects rat to human
Intraspecies	5	General population
DNEL	Value
For general population	150 mg/kg / (6 x 4 x 5) = 1.25 mg/kg bw/d

 

Long term general population (inhalation)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 150 mg/kg bw (OECD 422; oral; rat)	adverse clinical findings and decreased body weight gain
Step 2) modification of the starting point
	1/1.15	route to route (24h exposure)
	50/100	absorption oral to inhal.
Step 3) Assessment factors
Exposure duration	6	subacute to chronic
Interspecies	1	no interspecies extrapolation for inhal.
Intraspecies	5	General population
DNEL	Value
For general population	150 mg/kg x 0.5 / (1.15 x 6 x 1 x 5) = 2.17 mg/m³

 

 

Long term general population(dermal)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 150 mg/kg bw (OECD 422; oral; rat)	adverse clinical findings and decreased body weight gain
Step 2) modification of the starting point
	1/1	route to route
Step 3) Assessment factors
Exposure duration	6	subacute to chronic
Interspecies	4	extrapolation systemic effects rat to human
Intraspecies	5	General population
DNEL	Value
For general population	150 mg/kg / (6 x 4 x 5) = 1.25 mg/kg bw/d

 

 

Long term exposure general population (local effects)

 

Same considerations as for the worker.