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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
500 mg/m³
Additional information

No valid studies on toxicity to fertility for propylamine are available. However, a read-across to ethylamine (CAS No. 75-04-7), isopropylamine (CAS No. 75-31-0) and butylamine (CAS No. 109-73-9) is proposed to cover the inhalative route.

In a one-generation repeated dose inhalation reproductive toxicity study with isopropylamine (similar to OECD guideline 415), male and female rats were exposed for 6h/day and 5d/week to doses of 8, 41 and 204 ppm (20, 100 and 500 mg/m3) for 12-13 or 14-15 weeks, respectively (Monsanto 1988). No effects on mating or fertility parameters were seen at the highest dose of 204 ppm. With regard to effects on fertility the NOAEC was 204 ppm (500 mg/m3).

No valid studies on toxicity to fertility for ethylamine and butylamine are available.


Short description of key information:
No valid studies on toxicity to fertility for propylamine are available. However, a read-across to ethylamine (CAS No. 75-04-7), isopropylamine (CAS No. 75-31-0) and butylamine (CAS No. 109-73-9) is proposed.
In a one-generation inhalative reproduction toxicity study with isopropylamine on rats the NOAEC for fertility toxicity was 204 ppm (Monsanto 1988).

Effects on developmental toxicity

Description of key information
No valid developmental toxicity / teratogenicity studies for propylamine are available. Therefore, a read-across to ethylamine (CAS No. 75-04-7), isopropylamine (CAS No. 75-31-0) and butylamine (CAS No. 109-73-9) is proposed. 
In a one-generation inhalative reproduction toxicity study with isopropylamine on rats the NOAEC for developmental toxicity / teratogenicity was 204 ppm. In a prenatal inhalative developmental toxicity study with isopropylamine on rats the NOAEC was 408 ppm (Monsanto 1988). In a prenatal inhalative developmental toxicity study with butylamine on rats the NOAEC was 151 ppm (BASF AG 96/192, 2001).
Based on the most sensitive NOAEC the NOAEC for propylamine was 151 ppm (370 mg/m3).
In a prenatal oral developmental toxicity study with butylamine hydrochloride with female rats the NOAEL for teratogenicity was 67 mg/kg bw/d (BASF AG 92/377, 2002).
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
67 mg/kg bw/day
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
370 mg/m³
Additional information

In the one-generation inhalative reproduction toxicity study similar to OECD guideline 415 with isopropylamine, male and female rats were exposed for 6h/day on 5d/week to dose level of 8, 41 and 204 ppm (20, 100 and 500 mg/m3) for 12-13 and 14-15 weeks, respectively (Monsanto 1988). No effects on development were seen at the highest dose of 204 ppm. At examination of the offspring no treatment related effects were seen. With regard to developmental toxicity / teratogenicity the NOAEL was 204 ppm.

In the prenatal developmental inhalative toxicity study with isopropylamine similar to OECD guideline 414, rats were exposed for 10 days (6h/day) to doses of 20, 204 and 408 ppm (50, 500 and 1000 mg/m3, Monsanto 1988). At 408 ppm reduced ossification of the 13th rib and bent ribs were seen. These effects were not statistically significant and signs of maternal toxicity (decreased body weight and body weight gain, reduced abdominal fat, increased sneezing and nasal discharge as well as rales, laboured breathing) were seen at this dose level. In addition, no further effects on gestational parameters or prenatal development were seen. Therefore, the highest dose (408 ppm) was established as NOAEC in this study.

In a prenatal developmental inhalative toxicity study with butylamine according to OECD guideline 414, rats were exposed for 14 days (6h/day) to 17, 50 and 151 ppm (51, 151 and 460 mg/m3, BASF AG 96/192, 2001). Since no effects on gestational parameters and no signs of prenatal developmental toxicity were seen, the highest dose (151 ppm) was established as NOAEC.

In all available studies the highest dose tested was established as NOAEC for developmental toxicity / teratogenicity. Therefore, the most sensitive NOAEC was chosen to establish a NOAEC for propylamine. Thus, the NOAEC for propylamine was 151 ppm (370 mg/m3).

 

In an oral prenatal developmental toxicity study with butylamine hydrochloride according to OECD 414 female rats were treated with doses of 100, 400 and 1000 mg/kg bw/d on days 6-15 post coitum (BASF AG 92/377, 2002). The average frequency per litter of total external, soft tissue and overall malformations (mainly cardiovascular) was significantly increased at the highest dose group. In addition, signs of developmental toxicity, like slightly increased embryo lethality, reduced placental and fetal body weights as well as increased rate of fetuses with retarded ossification, were seen at 1000 mg/kg. At 400 mg/kg bw/d no signs of developmental toxicity but the same or similar malformations as at 1000 mg/kg bw/d were seen. At 100 mg/kg bw/d no signs of developmental toxicity and no malformations were seen. The NOAEL for teratogenicity was 100 mg/kg bw/d.

At 1000 mg/kg bw/d maternal toxicity (significantly reduced food consumption, body weight gain and mean gravid uterus weight as well as significantly increased number of resorptions and post-implantation losses) was evident. Therefore, the NOAEL for maternal toxicity was 400 mg/kg bw/d. The NOAEL for maternal toxicity and teratogenicity was corrected for butylamine itself (x 73.14g/mol/109.6 g/mol). Thus, with regard to teratogenicity the NOAEL for propylamine was set at 67 mg/kg bw/d. The NOAEL for maternal toxicity was established at 267 mg/kg bw/d.

 

The lowest observed adverse effect level (LOAEC) of 265 mg base/(kg bw*d) - which produced no maternal toxicity - would result in an exposure concentration of approx. 980 mg/m3#)- a concentration that produces severe nasal corrosion.

Even the oral NOAEL correlates with an exposure concentration which is too high as to be tolarable (240 mg/m3). This demonstrates that developmental adverse effects during pregnancy are very unlikely to occur, since potentially teratogenic concentrations cannot be tolerated by the host.

No valid reproductive toxicity data for propylamine, butylamine and isopropylamine via dermal route are available.

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#)Calculation: based on default values of 15.7 L/h (respiration volume female rat) and 0.35 kg body weight (female rat) (Guidance Chapter R.8, Table R.8 -17):

Exposure concentration C = dose / respiration volume per kg bw and day (here: exposure time per day = 6 h/d, rat):

C = [265 mg/(kg*d)] / [0.27 m3/6h]

= [265 mg/(kg*d)] / [0.27 m3/d]

= ~ 980 mg/m3

Justification for classification or non-classification

The read-across to butylamine, ethylamine and isopropylamine is considered reliable.

With regard to the oral route, indications of teratogenic effects were observed after repeated dose oral application of butylamine hydrochloride at doses that are not evidently maternal toxic.

With regard to the inhalative route, no indications of reproductive or developmental toxicity were seen even at the highest dose (151, 408 and 204 ppm, respectively) used in the studies.

These effects were only observed after repeated oral administration of doses above 100 mg/kg bw/d and the biological significance of this effect is not clear (OECD-SIDS, n-butylamine, Draft, 2005-11-19). Since the test substance is corrosive, an exposition of humans via oral route to doses that are capable to induce teratogenic effects is unlikely. Based on the data provided above, a classification for propylamine according to Directive 67/548/EEC and Directive EC/1272/2008 is not warranted.