Diallyldimethylammonium chloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1965

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented report which meets basic scientific principles but pre-dates GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1965

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline available

Deviations:

not specified

Principles of method if other than guideline:

To investigate the oral absorption, distribution, and excretion of diallyldimethylammonium chloride into blood, urine, faeces, expired air and selected tissues in rats.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diallyldimethylammonium chloride

EC Number:

230-993-8

EC Name:

Diallyldimethylammonium chloride

Cas Number:

7398-69-8

Molecular formula:

C8H16N.Cl

IUPAC Name:

diallyldimethylammonium chloride

Details on test material:

- Name of test material (as cited in study report): C14 Dimethyldiallylammonium chloride
- Physical state: white crystalline solid
- Analytical purity: >99%
- Impurities (identity and concentrations): none
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling): no data
- Specific activity (if radiolabelling): 0.68 mC/g
- Locations of the label (if radiolabelling): no data
- Expiration date of radiochemical substance (if radiolabelling): no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Radiolabelling:

yes

Remarks:

C14

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 113-252g
- Fasting period before study: no
- Housing: Roth metabolism chambers
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): dried Purina Rat chow combined with raw egg
- Water : ad libitum
- Acclimation period: two days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Animals were treated with 656 mg/kg (24 hours); 1585 mg/kg (48 hours) or 1591 mg/kg (72 hours) of C14 DADMAC (100 microcuries/ml: 100 microcuries/1.9 grams.)

No. of animals per sex per dose / concentration:

One

Control animals:

no

Positive control reference chemical:

no

Details on study design:

Following intubation with C14 DADMAC, for each animal per time point, urine, feces and expired air were collected at 24, 48 and 72 hours and frozen and radioactivity was determined.

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, expired air, blood, spleen, kidney , liver, bone marrow and three section of the gastrointestinal tract.
- Time and frequency of sampling: 24, 48 and 72 hours after intubation
- Other: Carcasses, after removal of skin and feet, were homogenized and radioactivity determined.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

No change in clinical signs was observed in the treated animals. There was a slight weight loss in the study. The primary route of excretion for C14 derived from DADMAC monomer was feces.

Samples C14 radioactivity	Animal	Treatment ( hours )			Cumulative excretion
		0 -24	24 -48	48 -72
Urine	1	1.3%	no	no	1.3%
	2	9.3 %	0.69%	no	9.99%
	3	8.5%	1.3%	0.31%	10.11%
Faeces	1	68.1%	no	no	68.1%
	2	51.7%	9.8%	no	61.5%
	3	21.3%	8.6%	0.28%	30.18%
Air (CO2)	1	0%	no	no	0%
	2	0.026%	0.047	no	0.073%
	3	0.016%	0.018%	0.012%	0.046%

The tissue levels for monomer were very low at each time point and there was no accumulation in any organ. The highest concentration of any organ was liver which had 0.0034% of the administered radioactivity

                        

Animal /weight	dose (mg/kg )	Blood	Tissues	Gastro intestinal	Carcass	Total C14excretion
1 / 108g	656	0.004%	0.03%			69.43%
2 / 153g	1585	0.002%	0.008%	0.006%	0.004%	71.62%
3 / 180g	1591	0.001%	0.005%	0.006%	0.02%	40.37%

                           

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
DADMAC was poorly absorbed. Of the tissues studied, the liver was found to have the largest percent uptake. The principle route of excretion was via the faeces followed by the urinary pathway with a very low amount being excreted via the expired air. The largest elimination was observed to occur during the first 24 hours.