2-(propyloxy)ethanol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

36 mg/m³

DNEL related information

Overall assessment factor (AF):

6

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.4 mg/kg bw/day

DNEL related information

Overall assessment factor (AF):

24

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:

no hazard identified

Additional information - workers

Key Study

Ref: Eastman Kodak Company (1989). EGMPE: A Subchronic Inhalation Study of Ethylene Glycol Monopropyl Ether in Rats Using a Functional Observational Battery and Neuropathology to Detect Neurotoxicity, Report TX-89-91, 07-04-1989.

 

This repeat dose study was considered the most reliable and was of longest duration (14 weeks).

 

Although EGMPE is currently rated for acute toxicity, category 4 (dermal), the acute dermal toxicity information available for this material was considered inadequate for determining a dose response or a LOEL/NOEL.  Guidance on this subject indicates that for most situations, a long-term DNEL is considered protective of acute effects and thus acute DNEL values do not need to be derived.

 

Corrected dose descriptors:

 

The starting point for a long-term (repeated dose) dermal systemic DNEL value for workers was the NOAEC value of 433 mg/m³ from a subchronic rat inhalation toxicity study (100 ppm).  This value was corrected for duration of exposure and for an increased respiratory volume for light work conditions (see Guidance Document, Chapter R.8.4.2).  A first-pass effect was discounted for the purposes of these calculations.

 

NOAEC_corr = NOAEC_rat x (6 hours/d) / (8 hours/d) x (6.7 m³/8 hours / 10 m³/8 hours)

 

or, NOAEC_corr = 217 mg/m³ (corrected inhalation dose descriptor)

 

Conversion to a dermal equivalent dose is performed as discussed in the Guidance Document, Appendix R.8-2, Example B.4.

 

NOAEL_dermal,rat = NOAEC_corr x sRV_rat (0.38 m³/kg bwt for 8 hour exposure)

 

or, 82 mg/kg bwt/day

 

Assessment factors

 

workers:

 

An AF of 4 was applied to the corrected dose descriptor for dermal long-term (repeated dose) systemic effects in workers (interspecies differences, allometric scaling). No further interspecies factor was applied. This recognizes the significant body of work available for the structurally similar material, ethylene glycol butyl ether, which has been shown to exert toxicity in rodents primarily through hemolysis of red blood cells with effects secondary to this in the liver, kidney and spleen. Blood from humans, including the elderly or those with other blood disorders, has been shown to be far less susceptible to this hemolytic effect (OECD, 1997; Ghanayem and Sullivan, 1993; Udden, 1994). An additional AF of 2 (subchronic to chronic) and an intraspecies (sensitive worker) AF of 3 were applied. The overall AF obtained was 24. The selection of these assessment factors was considered appropriate and conservative based on the assumed lack of sensitivity in humans to the primary hemolytic effect of the subject chemical.

 

No additional intraspecies (allometric scaling) factor was applied to the corrected dose descriptor for inhalation long-term systemic effects in workers.  An AF of 2 (subchronic to chronic) and an intraspecies (sensitive individual) AF of 3 were applied.  The overall AF obtained was 6.

References:

OECD (1997). SIDS Initial Assessment Report: 2-Butoxyethanol (CAS No. 111-76-2), for 6^thSIAM, Paris, 9-11 June 1997.

Ghanayem B.I. and Sullivan C.A. (1993). Assessment of the haemolytic activity of 2-butoxyethanol and its major metabolite butoxyacetic acid in various mammals including humans.” Human Exper. Toxicol.12: 305-311.

Udden M.M. (1994). Hemolysis and Decreased Deformability of Erythrocytes Exposed to Butoxyacetic Acid, a Metabolite of 2-Butoxyethanol: II. Resistance in Red Blood Cells from Humans with Potential Susceptibility. J Appl Toxicol 14:97-102.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.7 mg/m³

DNEL related information

Overall assessment factor (AF):

10

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:

2.2 mg/kg bw/day

DNEL related information

Overall assessment factor (AF):

40

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:

2.2 mg/kg bw/day

DNEL related information

Overall assessment factor (AF):

40

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

The starting point for long-term (repeated dose) oral and dermal systemic DNEL values for the general population was the NOAEC value of 433 mg/m³ from a subchronic rat inhalation toxicity study.  This value was corrected for duration of exposure (see Guidance Document, Chapter R.8.4.2).  A first-pass effect was discounted for the purposes of these calculations.

 

NOAEC_corr = NOAEC_rat x (6 hours/d) / (24 hours/d) x (5 days/week) / (7 days/week)

 

or, NOAEC_corr = 77 mg/m³ (corrected inhalation dose descriptor)

 

Conversion to a dermal (or oral) equivalent dose was performed as discussed in the Guidance Document, Appendix R.8-2, Example B.4.

 

NOAEL_rat = NOAEC_corr x sRV_rat (1.15 m³/kg bwt for 24 hour exposure)

 

or, 88 mg/kg bwt/day

 

Assessment factors

An AF of 4 was applied to the corrected dose descriptor for oral long-term (repeated dose) systemic effects in the general population (interspecies differences, allometric scaling).  In addition, an AF of 2 (subchronic to chronic) and an intraspecies (sensitive individual) AF of 5 were applied.  The overall AF obtained was 40.  These same AF values apply to the case of dermal exposure. For the reasons discussed above, these selected assessment factors were considered appropriate and conservative based on an assumed lack of human sensitivity to the hemolytic effects of the subject chemical.

 

No additional intraspecies (allometric scaling) factor was applied to the corrected dose descriptor for inhalation long-term systemic effects in the general population.  An AF of 2 (subchronic to chronic) and an intraspecies (sensitive individual) AF of 5 were applied.  The overall AF obtained was 10.