Dimethyldioctylammonium chloride

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 July 1998 - 16 January 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 451 - Carcinogenicity Studies

Version / remarks:

May 12, 1981

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

7173-51-5

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: B-1889

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: the stability of the substance was verified at before the inititation of the study and upon completion of the study.

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Experimental diets were analysed using a gas chromatography procedure. Homogeneity of the substance at each diet concentration was established. Prior to dosing, stability of the test substance in diets at the 100 and 1000 ppm concentrations was determined in stainless steel feeders and in the polyethylene storage containers. Diet concentrations were verified for all dose levels for the first four weeks of the study prior to administration of the diets to the animals. Thereafter, diets prepared every fourth week were analysed for concentration verification.

Duration of treatment / exposure:

Eighteen months.

Frequency of treatment:

Daily.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 ppm

Doses / concentrations 2

Dose / conc.:

100 ppm

Doses / concentrations 3

Dose / conc.:

500 ppm

Doses / concentrations 4

Dose / conc.:

1 000 ppm

No. of animals per sex per dose:

Sixty/sex/dose

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily, except for when detailed clinical observations were made.
- Cage side observations checked in table 2 were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once a week.

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly for the first 14 weeks and every other week thereafter.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- How many animals:10 animals/sex from the high dose and control groups during week 52; 10 animals/sex from all dose groups during week 79.
- Parameters were examined: erythrocyte count, haemoglobin, haematocrit, erythrocyte indices, platelet count, total leukocyte count.

Sacrifice and pathology:

Following the 78-week treatment period, the terminal necropsy of all surviving animals was undertaken. A complete necropsy was performed on each animal.

Results and discussion

Results of examinations

Clinical signs:

effects observed, non-treatment-related

Mortality:

mortality observed, non-treatment-related

Description (incidence):

The incidence of mortality for male mice (including those sacrificed moribund but excluding cage accidents) in the 0 (first control), 100, 500, 1000 and 0 (second control) ppm groups was 22%, 20%, 23%, 22% and 32%, respectively.
The incidence of mortality for female mice (including those sacrificed moribund but excluding cage accidents) in the 0 (first control), 100, 500, 1000 and 0 (second control) ppm groups was 28%, 20%, 25%, 20% and 17%, respectively.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

The mean absolute body weights and body weight gains for male mice in the top dose group were decreased relative to the untreated controls during most of the treatment period. The mean absolute body weights and body weight gains for female mice in the top dose group were decreased relative to the untreated controls during from the second week of treatment thorugh to the end of the study.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

Statistically significant differences in mean food consumption (incrases and decreases) were occassionally observed for males mice in the top tow dose groups, however these were considered by the authors to spurious staistical findings reflecting normal bilogical variation and not a response to treatment with the substance. No treatment-related effects were observed for females.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

Organ weight findings were statistically significantly different from both control groups in the top dose group for both sexes. This was considered by the study authors to be associated with the decreased overall body weight and not a direct effect of the treatment.

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Key result

Dose descriptor:

NOEL

Effect level:

500 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

No treatment-related changes, which could be considered adverse, were observed in male and female mice following dosing with the substance, when administered in powdered rodent diet for at least 78 weeks at the approximate concentrations of 100, 500 or 1000 ppm (corresponding to mean intake dose levels of 15, 76.3 and 155.5 mg/kg bw/day for the males and 18.6, 93.1 and 193.1 mg/kg bw/day for the females). The NOEL identified in this study was 500 ppm based on reduced weight and reduced weight gain in both sexes.

Executive summary:

Male and female mice were administered the substance in powdered rodent diet for at least 78 weeks at the approximate concentrations of 100, 500 or 1000 ppm (corresponding to mean intake dose levels of 15, 76.3 and 155.5 mg/kg bw/day for the males and 18.6, 93.1 and 193.1 mg/kg bw/day for the females). No treatment-related mortality occurred and no treatment-related clinical signs were observed during the study. There was no effect observed in the haematology parameters monitored. There were treatment-related changes observed in body weight and body weight gain, however this was not considered to be of toxicological relevance and thus not considered by the study authors to be adverse. Organ weight findings were statistically significantly different from both control groups in the top dose group for both sexes. This was considered by the study authors to be associated with the decreased overall body weight and not a direct effect of the treatment. No treatment-related findings were reported at post mortem macroscopic observations and histopathological examination. The NOEL identified in this study was 500 ppm based on reduced weight and reduced weight gain in both sexes.