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Description of key information

Only one repeated dose inhalative toxicity study with propylamine is available (Hine et al., 1960, no guideline followed). Doses of 200, 400 and 800 ppm propylamine were given to rats for 50 days (7h/d). Since no NOAEC could be determined in this study, the toxic potential of a repeated dose application was assessed from a read across to ethylamine (CAS No. 75-04-7), butylamine (CAS No. 109-73-9) and isopropylamine (CAS No. 75-31-0) based on structure similarity. 
The NOAEC in a repeated dose inhalation toxicity study with ethylamine (Lynch 1988) on rats was 100 ppm. In a one-generation repeated dose reproductive toxicity study with isopropylamine on rats the NOAEC for parental toxicity was 41 ppm (Monsanto 1988). In a prenatal developmental toxicity study with butylamine on rats the LOAEC for maternal toxicity was 17 ppm (BASF AG 96/192, 2001).
Based on these data, the most sensitive LOAEC of 17 ppm (42 mg/m3) was selected for propylamine.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEC
42 mg/m³
Study duration:
subacute
Species:
rat

Additional information

In the repeated dose inhalative toxicity study with propylamine doses of 200, 400 and 800 ppm (491, 981 and 1962 mg/m3) were given to rats for 50 days (7h/d). No guideline was followed and only limited data on results are available. At the lowest dose of 200 ppm a focal collection of lymphocytes in the myocardium was seen in one rat. Thus, no NOAEC could be established in this study (Hine et al., 1960). Therefore, a read across to ethylamine (CAS No. 75-04-7), butylamine (109-73-9) and isopropylamine (CAS No. 75-31-0) is proposed.

In the repeated dose inhalation toxicity study with ethylamine, rats were exposed to dose levels of 10, 100 and 500 ppm (18, 184 and 922 mg/m3) for 24 weeks (6h/d, 5d/week). Reduced body weight as well as histopathological changes of the nasal passage, like atrophic rhinitis in the anterior nasal passages and squamous metaplasia of nasal epithelium was seen at 500 ppm (Lynch, 1988). The NOAEC for local effects was 100 ppm (184 mg/m3).

In the one-generation repeated dose reproductive toxicity study with isopropylamine, male and female rats were exposed for 6h/day and 5d/week to dose level of 8, 41 and 203 ppm (20, 100 and 500 mg/m3) for 12-13 or 14-15 weeks, respectively (Monsanto 1988, see IUCLID chapter 7.8.1). The study was conducted similar to OECD guideline 415. Based on 2 mortalities and a lower body weight during the majority of the study at 203 ppm, the NOAEC for parental toxicity was set at 41 ppm.

In the prenatal developmental toxicity study rats were exposed for 14 days (6h/day) with butylamine to dose levels of 17, 50 and 153 ppm (51, 151 and 460 mg/m3, BASF AG 96/192, 2001). At 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. The LOAEC for maternal toxicity was set at 17 ppm.

 

Based on the data mentioned above the most sensitive LOAEC for butylamine was selected as LOAEC for propylamine.

 

No valid data for repeated dose toxicity after oral or dermal application of propylamine are available.

Justification for classification or non-classification

The read across to ethylamine, isopropylamine and butylamine is considered reliable and suitable for classification purposes of propylamine under EU Directive and 67/548/EEC and Directive EC/1272/2008. Local irritating effects on the respiratory tract were the main effects upon inhalative exposure of rats. A LOAEC of 42 mg/m3 was established for propylamine. According to Directive (EC) No. 1272/2008 the substance needs to be classified as may cause respiratory irritation (H335) and according toDirective 67/548/EEC as irritating to the respiratory system (R37). Both classifications, however are covered by the corrosiveness of the substance (H314 and R34, respectively).