Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.91 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.82 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

According to Annex VI of Directive 67/548/EEC propylamine is classified/labelled as harmful by inhalation, in contact with skin and if swallowed (R20/21/22) as well as corrosive (R34). The primary routes of industrial exposure to propylamine are via inhalation and skin contact.

Upon treatment of rabbit skin with propylamine for 24 hours under not further specified conditions all treated sites were thick and erythematous. In 3/6 animals surface dermatolysis was present which became dry, hard and concave, being characteristic of dry necrosis (Pennwalt 1977). To control risks of local dermal irritation a qualitative exposure assessment was performed. Though suitable for hazard assessment, the available experimental data do not allow for a quantitative risk assessment. Therefore, following the recommendations of Part E (Risk characterization) and Chapter R.13 (Risk Management Measures and Operational Conditions) of the REACh Guidance on Information Requirements and Chemical Safety Assessment, a qualitative risk assessment was performed for the dermal route. Based on its moderate corrosive properties, propylamine was allocated to the moderate hazard category. Appropriate risk management measures for the moderate hazard category given in Table E.3-1, Part E (Risk Characterisation) of the REACh Guidance on Information Requirements and Chemical Safety Assessment, were applied.

 

Local inhalative effects were considered to be a further critical endpoint for workers. However, no reliable repeated dose toxicity study with propylamine was available for DNEL derivation. Therefore, a read-across to other structural analogue primary alkylamines including ethylamine (CAS No. 75-04-7), butylamine (CAS No 109-73-9) and isopropylamine (CAS 75-31-0) was done.
In a repeated dose inhalation toxicity study, rats were exposed to ethylamine at doses of 10, 100 and 500 ppm (18, 184, 922 mg/m3) for 24 weeks (6h/d, 5d/week). The NOAEC for local effects was 100 ppm and the LOAEC was set at 500 ppm (Lynch, 1988). To derive a long-term inhalative DNEL the observed no effect level was modified according to guidance document R. 8 (ECHA, May 2008). An overall assessment factor (AF) of 10 (interspecies: 5; exposure duration: 2 [sub-chronic to chronic]; dose-response: 1; quality of whole database: 1) was applied and the derived inhalative long-term DNEL for ethylamine was 18.4 mg/m³ (10 ppm) for the worker.

The German authority (MAK-Commission) established a comparable OEL (5 ppm) which was also based on the study of Lynch (1988) as well as further reports. A TLV of 10 ppm (TWA) determined by the American Conference of Governmental Industrial Hygienists confirmed the reliability of the estimated long-term DNEL of 10 ppm for propylamine.

In a one generation repeated dose reproductive toxicity study, rats were exposed for 6h/day on 5d/week to 20, 100 and 500 mg/m3 to isopropylamine for 12-13 and 14-15 weeks (males and females), respectively (Monsanto 1988). No effects on mating or fertility parameters were seen at the highest dose of 500 mg/m3. On examination of the offspring no treatment related effects were seen. With regard to reproductive toxicity the NOAEL was 500 mg/m3. However, 2 males of the high dose group died. In addition, males of the high dose group had a significantly lower body weight during the majority of the study. With regard to parental toxicity 500 mg/m3 was assessed as LOAEL. The NOAEL was set at 100 mg/m3.

Applying the AF used for ethylamine (see above) the long-term DNEL for isopropylamine was 10 mg/m3 (4 ppm). The German MAK-Commission, however established an OEL of 5 ppm based on studies of Monsanto (1988) as well as further reports. The American Conference of Governmental Industrial Hygienists determined a TLV of 10 ppm (TWA) for isopropylamine.

In a prenatal developmental toxicity study, rats were exposed for 14 days (6h/day) to 51, 151 and 460 mg/m3 butylamine (BASF AG 96/192, 2001). On histopathology, changes of the respiratory epithelium in the nasal cavity, like infiltration of inflammatory cells and/or (multi) focal squamous cell metaplasia were seen in all dose groups. Focal necrosis of the nasal mucosa was only seen at the highest dose group. With regard to maternal toxicity the lowest dose group of 51 mg/m3 (17 ppm) was established as LOAEC. Since no effects on gestational parameters and no signs of prenatal developmental toxicity were seen, the highest dose (460 mg/m3) was established as NOAEC with regard to developmental toxicity.

In general, the German authority sets occupational exposure limits of aliphatic amines depending on their irritating properties on the respiratory tract. The breathing frequency of mice, oronasally exposed to 20 different amines for 15 minutes, was assessed by Gagnaire (1989). OELs for amines with a RD50 below 100 ppm are generally set at 2 ppm by the MAK-Commission. The RD50 of butylamine of 112 ppm would apply to an OEL of 5 ppm. Taking into account the strong irritating effects seen in the study of BASF AG (96/192, 2001), the MAK-Comission established an OEL of 2 ppm for butylamine.

In agreement, the American Conference of Governmental Industrial Hygienists determined a TLV of 5 ppm (ceiling limit) for butylamine.

 

Overall, the German MAK-Commission determined OEL values of 5, 2 and 5 ppm for ethylamine, butylamine and isopropylamine, respectively. In addition, the American Conference of Governmental Industrial Hygienists determined TLVs of 10, 5 and 5 ppm (TWA) for the respective amines. OELs and TLVs were based on local irritation effects on the respiratory tract. Due to the high consensus of the available OELs and TLVs and the high grade of structure analogy between the substances, a local long-term DNEL for propylamine was established at 2 ppm (= 4.91 mg/m3).

The German MAK-Commission established excursion factors of 2 for ethylamine (CAS No. 75-04-7), butylamine (CAS No 109-73-9) and isopropylamine (CAS 75-31-0), respectively. The short term DNEL was therefore calculated as 9.82 mg/m³. The Risk Management Measures and Operational Conditions corresponded to those used in the respective long-term scenario.

 

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Since propylamine is used at industrial and professional domains only, no exposure of the general population to propylamine is expected. Therefore no DNELs for the general population were calculated.