Quaternary ammonium compounds, bis(C16-18 and C18-unsatd. alkyl)dimethyl, chlorides

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

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

Adequacy of study:

other information

Study period:

1971

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

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

Adequacy of study:

other information

Justification for type of information:

For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

assessment report

GLP compliance:

no

Details on absorption:

Not determined.

Details on distribution in tissues:

Not determined.

Details on excretion:

Very little test substance was found in the urine from the highest feeding level. Tests on the lower feeding levels were negative within experimental error.
It was necessary to develop a background correction factor for the faecal analysis because each control sample exhibited a different background value. An average of 13% was eliminated in the faeces from the high dose group. Data for the high dose group are shown in Table 2.

Metabolites identified:

not measured

Table 2. Test substance excretion data from rats fed 2800 ppm.

Animal No. and Sex	Average Intake (mg)	Amount Recovered (mg)		% Recovered
		Faeces	Urine
1 M	64.7	5.7	0.007	8.8
2 M		22.8	0.045	35.3
3 M		2.2	0.01	3.4
Average				15.8
4 F	51.0	6.1	0.014	11.9
5 F		0.5	-	0.9
6 F		2.6	-	5.0
Average				5.9

Conclusions:

The authors concluded that significant amounts of the compound were metabolised by the rats.

Executive summary:

The study used as source investigated basic toxicokinetics.The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross reference “assessment report”.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1971

Report date:

1971

Materials and methods

Objective of study:

excretion

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides

EC Number:

263-090-2

EC Name:

Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides

Cas Number:

61789-80-8

Molecular formula:

R2Me2N(+)Cl(-) whereas R = mainly C16, 18-alkyl molecular weight range is based on R=14 (lower limit value) and R=18 (higher limit value)

IUPAC Name:

N,N-Dimethyl-N,N-di-n-alkyl(C16-18)-ammoniumchloride

Constituent 2

Reference substance name:

Dimethyl-di-"hydrogenated tallow" ammonium chloride

IUPAC Name:

Dimethyl-di-"hydrogenated tallow" ammonium chloride

Details on test material:

Dimethyldihydrogenated tallow ammonium chloride manufactured by the Armour Industrial Chemical Company.

Radiolabelling:

no

Test animals

Species:

rat

Strain:

other: Charles River albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

Charles River albino rats, obtained from Charles River Breeding Laboratories, Massachusettes. Rats were fed ad libitum. They were housed individually in standard wire-bottomed steel cages.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

The test substance was provided in the diet at 3 levels. The appropriate amount of test substance was mixed with the standard rat diet ration in a Hobart mixer. Fresh diets were prepared each week, and each rat was offered an amount of diet sufficient for 1 week's ad libitum feeding.

Duration and frequency of treatment / exposure:

91 days, provided daily in the diet. The parents of these rats were also exposed for approximately 4 weeks prior to mating.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 7, 140 and 2800 ppm.

No. of animals per sex per dose / concentration:

3 males and 3 females per dose.

Control animals:

yes, plain diet

Positive control reference chemical:

Not examined.

Details on study design:

A 90 day feeding study was conducted at Industrial BIO-TEST laboratories with groups of rats who were the offspring of previously exposed rats. At the end of the 90 day feeding study, some of the rats were maintained on the diet for an extra 24 hours and housed in metabolism cages for the collection of urine and faeces. Average dose levels per day were calculated based on body weights and individual feed consumption during the last six weeks of the feeding study (see Table 1).

Details on dosing and sampling:

24 hour urine and faeces were collected and frozen separately. The samples were analysed for quarternary compound content at Armour Industrial Chemical Company Laboratories. Samples were extracted with chloroform prior to colorimetry analysis.

Statistics:

None reported.

Results and discussion

Preliminary studies:

Not applicable.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not determined.

Details on distribution in tissues:

Not determined.

Details on excretion:

Very little test substance was found in the urine from the highest feeding level. Tests on the lower feeding levels were negative within experimental error.
It was necessary to develop a background correction factor for the faecal analysis because each control sample exhibited a different background value. An average of 13% was eliminated in the faeces from the high dose group. Data for the high dose group are shown in Table 2.

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

Table 2. Test substance excretion data from rats fed 2800 ppm.

Animal No. and Sex	Average Intake (mg)	Amount Recovered (mg)		% Recovered
		Faeces	Urine
1 M	64.7	5.7	0.007	8.8
2 M		22.8	0.045	35.3
3 M		2.2	0.01	3.4
Average				15.8
4 F	51.0	6.1	0.014	11.9
5 F		0.5	-	0.9
6 F		2.6	-	5.0
Average				5.9

Applicant's summary and conclusion

Conclusions:

The authors concluded that significant amounts of the compound were metabolised by the rats.

Executive summary:

Albino rats were fed with the test substance in the diet as part of a separate 90 day feeding study (Smith & Plank, 1971). At the end of the study they were maintained on the diet for a further 24 hours for collection of urine and faeces in metabolism cages.

The excretion of the quarternary compound in the urine and faeces was determined by colorimetry following chloroform extraction.

At lower dietary levels (7 and 140 ppm) virtually no quarternary compound was recovered.

At the higher dietary level (2800 ppm) an average of 15% was excreted by males and 5.9% by females, with the majority of excreted compound being found in the faeces.

The authors concluded that significant amounts of the compound were metabolised.