Dimethylammonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

Report-Date 1980-05-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Principles of method if other than guideline:

Method: other: BASF-Test, experimental result

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethylamine

EC Number:

204-697-4

EC Name:

Dimethylamine

Cas Number:

124-40-3

IUPAC Name:

N-methylmethanamine

Details on test material:

- Name of test material (as cited in study report): Dimethylamin, 40%-ige waessrige Loesung



- Name of test material (as cited in study report): Dimethylamin, 40%-ige waessrige Loesung

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gassner
- Weight at study initiation: male 192 g (mean); female 160 g (mean)
- Diet: Herilan MRH-Haltung, Heinrich Eggersmann KG, Rinteln

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: dissolved in water with 0.5 % CMC

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 6.81 - 46.4 %
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

681, 1000, 1470, 2150, 3160 and 4640 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

ca. 1 000 mg/kg bw

Mortality:

No animal died in the lowest dose group. Four out of 10 died in the 1000 mg/kg group. All animals died in the four highest dose groups.

Clinical signs:

other: staggering, atony, spatic gait, exsiccosis, tremor, salivation, opisthotonus, poor general state, reduction in body weight, "morphinschwanz"

Gross pathology:

Animals that died:
Heart: acute dilatation and congestive hyperemia
Lung: slight emphysema
Gastro-intestinal tract: redness, bloody content
Liver: peripheral lobule marking

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dimethylamine 40 % aqueous solution was harmful after oral gavage to Spraque-Dawley rats (according to C&L Regulations No. 1272/2008). An LD50 was deduced: 1000 mg/kg bw.

Executive summary:

BASF conducted in 1980 an oral acute toxicity testing in Sprague-Dawley rats with dimethylamine 40 % aqueous solution. The substance was administered to the rats via oral gavage (Concentration in vehicle: 6.81 - 46.4 %, max. dose applied: 10 ml/kg). The different doses were 681, 1000, 1470, 2150, 3160 and 4640 mg/kg. After the observation period of 14 days (clinical signs were recorded), all animals were necropsied and additionally histopathological examinations were performed. In the lowest dose group (each group consisting of 10 animals) no animal died. In contrast in the group dosed with 1000 mg/kg bw, 4 of 10 animals died, and all animals in the higher dosed groups died. The clinical signs of the treated animals were staggering, atony, spatic gait, exsiccosis, tremor, salivation, opisthotonus, poor general state, reduction in body weight and a "morphinschwanz". Necropsy and histopathological examinations revealed in the animals that died an acute dilatation and congestive hyperemia of the heart, slight emphysema of the lung, redness and bloody content in the gastro-intestinal tract and peripheral lobule marking in the liver. In conclusion a LD50 of 1000 mg/kg bw was deduced.

In the present study, DMA aqueous was used. The substance is known to be corrosive and toxic if swallowed or inhaled. The substance Dimethylamine hydrochloride (CAS-No. 506-59-2, EC-No. 208-046-5) is a near analogue to Dimethylamine (CAS-No. 124-40-3, EC-No. 204-697-4). Merely from comparing the molecular structures of those two substances it is apparent that Dimethylamine hydrochloride (Dimethylammonium hydrochloride; DMA-HCl) and Dimethylamine (DMA) are closely related to each other. DMA-HCl is the chloride of DMA or morespecifically, the gas DMA reacts with hydrochloric acid to form the salt DMA-HCl, an odourless white solid. At this DMA`s unshared electron pair on nitrogen forms a coordinate bond with the proton hydrogen, accompanied by chlorine bonding ionically. If alkali (e.g. sodium hydroxide) is added to solutions of DMA-HCl the free amine DMA will be liberated. Hence, under specific conditions the toxicological and ecotoxicological properties of the gaseous substance DMA and its salt DMA-HCl (even in aqueous solution) are equal and as a result, read across is justified. Similar to the native DMA, DMA HCl will exert its toxicity in the same range of severity because of its dissociation to free amine in weak alkali body fluids.

Classification is warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

DMA HCl has been classified according to DSD as: Xn, R22 Harmful, Harmful if swallowed;

DMA HCL has been classified according to GSH: Acute Tox. 4, H302: Harmful if swallowed.