Pyrrolidine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.4 mg/m³

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

3

Dose descriptor:

NOAEC

AF for dose response relationship:

1

AF for differences in duration of exposure:

1

AF for intraspecies differences:

3

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Most sensitive endpoint:

skin irritation/corrosion

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:

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

Pyrrolidine is a cyclic amine. Based on Regulation (EC) No. 1272/2008 (CLP), the test substance is classified for acute inhalation toxicity with Cat 4 (H332 - Harmful if inhaled), for acute oral toxicity with Cat 4 (302 - Harmful if swallowed) and for skin corrosion with Cat 1A (H314 - Causes severe skin burns and eye damage).

Pyrrolidine is a colorless to yellow, flammable liquid with ammonia-like odor, a very strong base with a pH of 12.9 at 20 °C (Gestis Substance Database, 2013), and exhibit therefore severe corrosive properties. The moderate vapour pressure of about 64.5 hPa at 20 °C (GESTIS 2011, see chapter “vapour pressure”) indicates that exposure by the inhalation route may be possible under ambient conditions.

Thus, the primary routes of anticipated industrial exposure to the substance may occur via inhalation and skin contact.

Acute / short-term exposure - local effects

There are four acute inhalative toxicity studies available, not performed under GLP principles and OECD guidelines, but however valuable. Nevertheless, the data were not suitable to derive a NOAEC necessary for calculation of an acute toxicity DNEL. However, the derived DNEL for long-term exposure of 8.4 mg/m³ sufficiently covers short-term exposure.

Long-term exposure - local effects

There are animal data available concerning repeated dose toxicity for the test item. A subacute repeated dose inhalation (6 hours per day, 5 days per week) study in rats was performed under GLP conditions according to OECD Guideline 422 (BASF 87R0021/121005, 2013).Exposure related local effects were observed in rats exposed to 150 mg/m³ (BASF 87R0021/121005, 2013).The inhalation study was selected as the endpoint for DNEL derivation and the no-observed adverse effect concentration (NOAEC) for local toxicity of the test substance was set to 50 mg/m³) for male and female rats. No NOAEC for systemic toxicity was determined.

As point of departure for DNEL derivation for local exposure following dermal and inhalation contact, the local NOAEC of 50 mg/m³ was taken.

DNEL inhalative long-term - local

For derivation of the inhalative DNEL, allometric scaling was performed as recommended in the "Guidance on information requirements and chemical safety assessment”, Chapter R.8 (ECHA 2012). Thereby, due to the 6 h/d inhalatory rat study, the starting point was corrected for the different exposure duration of workers of about 8 h/d and for differences between the 8 -hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (* 6 h/d / 8 h/d * 6.7 m³/10 m³).

The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 25.13 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

• Interspecies factor: 1

Besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to humans as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans have to be taken into account.

• Intraspecies factor: 3

Concerning the intraspecies factor, an assessment factor of 3 as recommended by REACh Guidance Document R.8, ECHA (2012).

• Exposure duration: 1

Based on the local effects, the assessment factor for exposure duration extrapolation of 1 was used as recommended by ECETOC TR 110 (2010).

• Dose-response: 1 (default)

• Quality of whole database: 1 (default).

Total AF = 3

Based on this calculation the resulting DNEL for long-term inhalation is 8.4 mg/m³.

DNEL calculation is based on  

·        ECHA (2012). REACh Guidance Document R.8.

·        ECETOC (2010). Guidance on Assessment Factors to Derive DNELs. ECETOC Technical Report No. 110.

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 consumer uses have been identified, and exposure to the general population is not expected. Therefore DNELs and/or DMELs for the general population have not been established.