Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
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:
reference to other study

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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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:
3 males and 3 females per dose.
Control animals:
yes, plain diet
Positive control:
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.