Registration Dossier

Administrative data

Description of key information

Oral: BASF, Gewerbetoxikologische Grundprüfung, 1980.
Dermal: BASF, Gewerbetoxikologische Grundprüfung, 1980.
Inhalation: International research and development corporation, 1992, rats (1 hour exposure) (for C&L).

Inhalation: Gagnaire, 1989, mice (for DNEL derivation).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
1 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
9 900 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
3 900 mg/kg bw

Additional information

In an oral acute toxicity study performed by BASF AG in 1980, DMA was administered to rats (test group consisting of 5 rats, strain: Sprague-Dawley/sex) by single gavage with an aqueous solution of the test substance. Observations for mortality and for clinical symptoms of toxicity were performed. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. The initial concentrations were 681, 1000, 1470, 2150, 3160 and 4640 mg/kg bw. As effect level the LD50 was considered to be around 1000 mg/kg bw. No animals died in the lowest groups, but 4/10 died in the dose group with 1000 mg/kg bw. All animals died in the 4 highest dose groups. Animals showed staggering, atony, spatic gait, exsiccosis, tremor, salivation, opisthotonus, poor general state, reduction in body weight, "morphinschwanz”. The test substance caused systemic toxicity (including mortality) and local irritation in a dose dependent manner.

The International Research and Developmental Corporation tested in 1992 the acute toxicity by inhalation of dimethylamine with rats (strain: Charles River Crl:cd BR VAF/Plus; Sprague-Dawley derived). The route of exposure was inhalation by whole body exposure. The exposure times were 6 - 60 minutes with different concentrations (ranging from 4,620 to 19,900 ppm). Different clinical signs, changes in body weight and also mortality (20, 40, 50, 50, 60% deaths (6 min exposure), 0, 40, 50, 50, 80 % death (20 min exposure), or 20, 10, 40, 70 and 80 % death (60 min exposures)) was reported. So 3 different LC50 were determined: LC50(6min) = 17600 ppm (32.9 g/m³/6 min), LC50(20min) = 7340 ppm (13.7 g/m³/20 min) and LC50(60min) = 5290 ppm (9.9 g/m³/60 min).

An inhalation acute toxicity test was performed by a dynamic inhalation method by BASF AG (1979). Each 10 male and female rats (strain: Sprague-Dawley) were exposed to whole body gas inhalation within a time period of 4 hours. After the 4 h DMA exposure, the animals were observed for 14 days. The concentration of the test substance was nominal 7.23 mg/L (analytical: 5.87 mg/L). The LC50 value was determined to be greater than 5.9 mg/L air for both sexes. No animal died. Clinical symptoms occurring during exposure were: eye and nasal secretion, dyspnea, salivation, hunched posture, smeared fur, closed eyelid, high-stepping gait, snout wiping and flatulence.

The effects of DMA on the respiratory tract were investigated by Gross and colleagues in 1987. The distribution of lesions found in this study indicates that there is possibly a high rate of deposition of DMA in the anterior nasal passage. Gross et al. (1987) concluded that DMA toxicity is primarily attributable to the irritant properties of the parent compound with a possible role for the metabolites of DMA. The direct cytolethal effects of DMA causing frank tissue damage are most likely due to the one or both of these mechanisms. It is of interest that despite severe tissue destruction in the anterior nose following a single 6-hr exposure, the nasal lesions exhibited very little evidence of progression, even after 2 years of exposure. These findings indicate a possible regional susceptibility to DMA toxicity or a degree of adaptation by the rat to continued DMA exposure. Effects of DMA on nasal mucociliary function were apparent after a single 6-hr exposure and they exhibited minimal progression throughout the acute study. DMA-induced effects included almost complete reversal of mucus flow and ciliary beat in one region of the lateral wall and clear modification of flow patterns to provide clearance around areas of turbinate and septal destruction. Mucus pooling, seen between and over the turbinates of DMA treated rats, indicates that while the mucociliary apparatus can respond to damage by altering mucus flow patterns, it may not function optimally under these conditions. DMA-induced alteration of mucus flow patterns and ciliary beat direction may provide a useful tool for studies of factors which control this complex clearance system in the nose. The vacuolation of epithelial cytoplasm, induced by acute DMA exposure, was very severe in affected areas and was seen in both ciliated and nonciliated epithelial cells and ducts of underlying glands of the respiratory mucosa, while in the olfactory epithelium this change was largely confined to sensory cells.

BASF AG performed a test for acute toxicity by dermal application in 1980. Dimethylamine was applied once for 24 hours to the clipped skin of the back and flank (area about 48 cm2) unchanged in a dose of 5000, 4000, 3200, 2500 or 400 mg/kg bw. The coverage of the treated area was creating occlusive conditions. The treated area of skin was then covered with an inert foil, which was secured in position with adhesive tape. The bandage was removed after an exposure period of 24 hours; subsequently, the test substance was washed off with warm water or a mixture of water/Lutrol and dried with cellulose. Mortality was observed as well as abnormalities in gross pathology. Clinical signs were systemic (apathy, convulsions, crying). With the highest dosage 6 animals died after 24 hours, as well as with a dosage of 4000 mg/kg bw; whereby another animal died after 48 hours. By application of dimethylamine in a concentration of 3200 mg/kg bw one animal died after 1 hour and two more animals after 24 hours. Just one animal died after 24 hours by the usage of 2500 mg/kg bw and no mortality occurred by a dosage of 400 mg/kg bw. Pathology performed revealed: acute dilatation of the heart, congestive hyperemia, peripheral lobule marking in the liver, and edema in the lung.

The expiratory bradypnoea indicative of upper airway irritation in mice was evaluated during oronasal exposure to increasing concentrations of twenty aliphatic amines (Gagnaire et al., 1989).The breathing frequency was monitored before and during a 15-min exposure period. For each measurement, the maximum decrease in respiratory rate was recorded. Four to six different exposure concentrations were used, and six previously unexposed mice were used at each level. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each test compound.

For DMA, the onset of action was very rapid, ca. 30 s to 1 min. At the end of a 15-min exposure period, the recovery of respiratory frequencies to the pre-exposure values was also rapid, ca. 1 min. The different exposure concentrations produced a broad range of effects.

Previous studies with several chemicals have shown that the RD50 values can be used successfully to predict safe industrial exposure. At 0.1 RD50, humans would experience some slight discomfort and this should be the highest level permitted in industry. At 0.01 RD50 no sensory irritation is observed and a convenient threshold limit value (TLV) would be 0.3 RD50 the midpoint on a logarithmic scale between the 0.1 and 0.01 RD50. For dimethylamine, a TLV of 10 ppm seems too high and should be divided by a factor of two.

In conclusion, the experimental results indicate, that dimethylamine is of low acute toxicity in mammals: LD50rat (oral) > 1000 mg/kg

bw/day, or a LC50rat (inhalative, 4 hours) >5.9 mg/m³, LD50rat (dermal) > 3900 mg/kg bw/ day. The main symptoms following exposure were eye and nasal secretion, dyspnea, salivation, hunched posture, smeared fur, closed eyelid, high-stepping gait, snout wiping, flatulence. The key study performed by the International Research and Development corporation, 1992, identified even 3 different LC50with unusual exposure durations. Still this study provides a lot of qualified and useful information. The results obtained from the experiments fit really well to the results of BASF 1979, therefore the values will be used for Classification and Labelling. The more sensitive RD50 value (causing a 50% decrease of the respiratory rate of mice) derived from the results of Gagnaire 1989 will be used for the derivation of the acute inhalation DNEL for local effects.

Justification for classification or non-classification

Classification for acute toxicity is needed according to DSD and GHS:

DMA has been classified according to DSD as:

Aqueous: Xn, R 20 / R22 Harmful, Harmful by inhalation and if swallowed;

Gaseous: Xn, R20 Harmful, Harmful by inhalation.

DMA has been classified according to GSH:

Aqueous: Acute Tox. 4, H302: Harmful if swallowed; H332: Harmful if inhaled; STOT -SE Cat 3, H335: May cause respiratory irritation, Affected organs: respiratory tract, lungs;

Gaseous: Acute Tox. 4, H332: Harmful if inhaled; STOT - SE Cat 3, H335: May cause respiratoty irritation, Affected organs: respiratory tract, lungs.

The distinction made for aqueous solution and gas are necessary, because in the solution the concentration of DMA might vary. Concerning the gas the concentration of it is always alike. Therefore different classifications for the both states are made.