3-dimethylaminopropan-1-ol

Endpoint summary

Description of key information

Since it is likely that Dimethylaminopropanol will be absorbed and in the absence of substance-specific absorption data, the default absorption values from the REACH guidance (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation and 50% for oral absorption. No default factor (i.e. factor 1) is applied when inhalation-to-dermal extrapolation is performed in accordance with Section R.8.4.2.

Additional information

No data are available that describe the toxicokinetics of dimethylaminopropanol, therefore relevant substance properties and data from toxicity studies indicating systemic bioavailability were taken together to assess the general toxicokinetics of the substance.

Physical-chemical properties

Dimethylaminopropanol is a liquid with a molecular weight of 103.2 g/mol. The log Pow is -0.23 at 25 °C and pH 10.7, and -2.59 at 25 °C and pH 7.2. The solubility in water is 1000 g/L at 20 °C.

 

Data from acute and repeated dose toxicity studies

In an acute oral toxicity study rats were administered dimethylaminopropanol at 3.5, 283, 354, 442, 849 and 1697 mg/kg by single dose (gavage) followed by a 7-day observation period (BASF AG, 1969). Clinical signs included dyspnoea and staggering. Findings at necropsy included serious incrusted snouts, liquid-proliferative serous skin(s) and diarrhea. The LD50 was 354 - 442 mg/kg bw. In another acute oral toxicity study, comparable to OECD guideline 401, Sprague-Dawley rats (5/sex/dose) were administered dimethylaminopropanol at 1470 to 10000 µl/kg (equivalent to 1299 to 8840 mg/kg) by single dose (gavage) followed by a 7-day observation period (BASF AG, 1975). Clinical signs included dyspnoea, slight staggering, partly ventral position and reddished salivary secretion. Findings at necropsy included acute dilatation of the heart, congestive hyperemia, distinct diffuse reddening especially in the glandular stomach, partly bloody slough eschar formation and hematinised diarrheic intestine content. The LD50 was 2100 µL/kg bw (equivalent to ca. 1860 mg/kg bw). 

Two reports are available in which rats were exposed to a saturated dimethylaminopropanol atmosphere (concentration not given) at 20°C. In one study no deaths were observed during a 7-day observation period after 1 hour of exposure, after 3 hours of exposure 1 out of 12 rats died during the 7-day observation period and after 8 hours of exposure 2 out of 6 rats died during the 7-day observation period (BASF AG, 1969). In this study rats were also exposed to a saturated dimethylaminopropanol atmosphere generated at 150°C, after 30 minutes of exposure no deaths were observed, after 1 hour of exposure 1 out of 12 rats died and after 3 hours of exposure 4 out of 6 rats died.

In the second study after 3 hours of exposure no deaths were observed during a 7-day observation period, at 8 hours of exposure 1 out of six rats died during the 7-day observation period (BASF AG, 1976).

No reliable acute and repeated dermal toxicity data is available. 

No repeated dose toxicity study is available for dimethylaminopropanol. Dimethylethanolamine (DMAE, CAS 108-01-0) is a structural analogue of dimethylaminopropanol (see also IUCLID chapter 13). In the two-week inhalation study (Klonne et al., 1987), rats exposed to higher concentrations of DMAE vapour (98, 288 and 586 ppm) during an 11 -day period exhibited severe signs of respiratory and ocular irritation (except the 98 ppm group). All animals of the 586 ppm group and 4 of 15 male rats of the 288 ppm group died. Body weight values for the 288 ppm group were reduced to about 75% of preexposure values, while the 98 ppm group gained 35% less weight than controls. Statistically significant differences in clinical pathology parameters (288 ppm group) and in organ weight values (288 and 98 ppm groups) probably resulted from the decreased food consumption and not from specific target organ toxicity. In the groups evaluated histologically (the 98 and 288 ppm groups) the eye and nasal mucosa were the primary target organs.

In a 13-week sub-chronic study, F-344 rats were exposed to 0, 8, 24, or 76 ppm DMEA for 6 hr/day, 5 days/week for 13 weeks (Klonne et al., 1987). No animals died during the study. The body weight gains for both sexes of the 76 ppm group were statistically significantly lower than control values for most of the latter half of the 13-week exposure time. The body weight gain values for the 76 ppm group returned to control values during the recovery period. There were no expossure-related of body weight gain for rats exposed to 8 or 24 ppm of DMEA. There were no exposure-related effects on the neurobehavioral, food and water consumption, hematologic, serum chemistry, or urinalysis evaluations, on organ weights, or on the gross appearance of organs. Exposure-related nasal lesions were observed histologically at the termination of exposures in both sexes of the 76 ppm group, but were generally not observed in rats of the 24 ppm group. The lesions were limited to the anterior nasal cavity and included squamous metaplasia, microcysts and mucous cell hyperplasia of the respiratory epithelium, mild rhinitis and atrophy of the dorsal olfactory epithelium. The incidence and severity of these lesions were decreased at the end of the recovery period, indicating some degree of repair. Additionally, 4/10 males had laryngitis and two of these rats also had tracheitis. No similar lesions were found in female rats. Vacuolization of the corneal epithelium was observed in 3/10 female rats of the 76 ppm group at the termination of exposures but not at the end of the recovery period. Corneal opacity occurred in the 24 and 76 ppm groups at the end of the daily exposure, beginning approximately 2-3 weeks after initiation of exposures. The opacity regressed during the night-time nonexposure hours. There was also a moderate incidence (approximately 25%) of audible respiration in rats of the 76 ppm group. 

Absorption, distribution, metabolism, excretion

No data on absorption are available. Therefore for the DNEL derivation the default as reported in the REACH guidance will be used; an absorption of 50% is assumed for the oral route; and an absorption of 100% is assumed for the inhalation route. No default factor (i.e. factor 1) is applied when inhalation-to-dermal extrapolation is performed in accordance with Section R.8.4.2.