Prop-2-yn-1-ol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

other: MAK value derivation (OEL)

Overall assessment factor (AF):

2.5

Modified dose descriptor starting point:

NOAEC

Value:

11.6 mg/m³

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

9.4 mg/m³

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

9.4 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Overall assessment factor (AF):

6

Dose descriptor starting point:

NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.83 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

24

Modified dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

not necessary, since the exposure route of the original study was the dermal application

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

2

Justification:

default value for time extrapolation from subchronic to chronic

AF for interspecies differences (allometric scaling):

2.4

Justification:

default value for correction of differences in metabolic rate (rabbit to human)

AF for intraspecies differences:

5

Justification:

default value (worker)

AF for the quality of the whole database:

1

Justification:

guideline study

AF for remaining uncertainties:

1

Justification:

toxicodynamic differences between humans and rabbits are not assumed; therefore, the assessment factor for remaining differences is set to 1

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Long-term exposure - local effects

inhalation

Local toxicity was seen in several inhalation toxicity studies in the nasal cavity of rats and mice, mainly in the form of histopathological changes on the respiratory and olfactory epithelium. Subacute, subchronic and chronic studies in mice and rats were performed. The LOAEC and NOAEC values obtained in these studies for effects in the nasal cavity are shown in the following table:

Study duration	Species	LOAEC [ppm]		NOAEC [ppm]		Reference
		female	male	female	male
14 -d	mouse	n.e.	88	n.e.	25	Zissu, 1995
	rat	50	50	10	10	BASF, 1990
90 -d	mouse	16	16	8	8	NIH, 2008
	rat	8	16	4	8	NIH, 2008
2 -y	mouse	8	8	<8	<8	NIH, 2008
	rat	16	16	<16	<16	NIH, 2008

The data show that mice and rats are of comparable sensitivity regarding local effects in the nose. In the chronic toxicity study a NOAEC could not be established because histopathological changes in the nasal cavity were still found at the lowest exposure concentration of 8 ppm and 16 ppm in mouse and rat, respectively. Applying a LOAEC to NOAEC assessment factor of 3 to the lowest chronic LOAEC of 8 ppm leads to a calculated NOAEC of 2.7 ppm. This chronic NOAEC is in very good agreement with the chronic NOAEC of 2.0 - 2.7 ppm which arises from the extrapolation of the lowest subchronic NOAEC of 4 ppm to the chronic situation using a time extrapolation factor in the range of 1.5 to 2. The chronic NOAEC of 2.0 - 2.7 ppm is two-fold lower than the corresponding NOAEC of 5 ppm derived for systemic effects (see above). The NOAEC of 2.0 - 2.7 ppm is based on local toxic effects in the rodent nose. Due to the higher respiration frequency and volume/kg bw rodents are more susceptible for the kind of observed lesions than humans. Therefore, the application of an additional assessment factor to the NOAEC for the derivation of a local long-term exposure DNEL is not needed. Thus, a local DNEL (long term inhalation exposure) of 2 ppm (or 4.7 mg/m³) can be derived from the available data, confirming the German OEL (= MAK value) of 2 ppm. Therefore, the DNEL for systemic effects after long term exposure is considered to ensure a sufficient level of protection for the local effects following long term inhalative exposure.

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

Currently, a consumer use of propargyl alcohol is not foreseen. Since no consumer use is planned, a derivation of the DNELs for general population does not affect risk characterization at all.