Quaternary ammonium compounds, di-C14-18-alkyldimethyl, Me sulfates

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1976

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

2001

Materials and methods

Principles of method if other than guideline:

as deduced from study description similar to OECD 408

GLP compliance:

no

Remarks:

pre-guideline study

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, Me sulfates

EC Number:

263-091-8

EC Name:

Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, Me sulfates

Cas Number:

61789-81-9

Details on test material:

- Name of test material (as cited in study report): UDL-1017 (CAS RN 61789-81-9; Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, Me sulfates)
- Purity: not stated

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Duration of treatment / exposure:

Treated and control diets were available continuously

Frequency of treatment:

7 days/week, 13 and 21 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.25, 0.5 and 10% in the diet (0 and approximately 170, 365, and 750 mg/kg/day actual ingested)
Basis:
nominal in diet

No. of animals per sex per dose:

20

Details on study design:

Citation from secondary source:
Groups of forty rats (20 males and 20 females) were
administered the test substance orally at concentrations of
0.25, 0.5 and 10% in the diet. Rats were offered the diet
continuously. Initially, the study was scheduled to be run
for 13 weeks; however, after evaluation of the 13-week
necropsy data revealed evidence of compound-related
lesions, the remaining rats were dosed an additional nine
weeks. Appropriate amounts of the test substance were
mixed with Mazola Corn Oil and incorporated into
standard laboratory diet weekly. Upon arrival at the
laboratory, rats were four to five weeks old. Just prior to
treatment, body weight ranges for males and females were
98 to 160 g and 107 to 151 g, respectively. Rats were
observed daily for physical appearance, signs of local or
systemic toxicity, pharmacologic effects or mortality.
Ophthalmoscopic examinations were conducted pretest and
in week 13. Body weights were taken twice pretest, weekly
during treatment and at terminal sacrifice (after fasting).
Food consumption was recorded weekly beginning one
week prior to treatment. During weeks 4 and 13, five
rats/sex/group were randomly selected for hematology
(hemoglobin; hematocrit; erythrocytes; total and
differential leukocytes; erythrocyte morphology; and mean
corpuscular volume, hemoglobin and hemoglobin
concentration) and clinical chemistry (serum glutamic
pyruvic transaminase; alkaline phosphatase; blood urea
nitrogen; fasting glucose; total protein; albumin; globulin;
and A/G ratio) evaluations. During week 13, five
rats/sex/group were randomly selected for urinalysis (gross
appearance; protein; glucose; pH; specific gravity; ketones;
bilirubin; and occult blood) evaluations. Forty rats
(five/sex/group) during week 4 (34 days of treatment),
60 rats (ten/sex for control and high groups and five/sex for
remaining two groups) during week 13, and 60 rats
(five/sex for control and high groups and ten/sex for
remaining two groups) during week 22 were sacrificed and
necropsies conducted. The following organs were weighed
and organ/body weight ratios calculated: pituitary,
adrenals, gonads, heart, kidneys and liver. The following
tissues were preserved from all animals and examined
histopathologically for the control and high dose groups
(five/sex at 4 weeks and 22 weeks and ten/sex at
13 weeks): adrenals, bone (rib junction), bone marrow
(sternum), brain (two sections with meninges), esophagus,
eye (with optic nerve), gonad (testis, epididymis, ovary,
oviduct), heart (with coronary vessels), intestine (cecum,
colon, duodenum, ileum, jejunum), kidney, liver, lung,
lymph node (mesenteric, pulmonary), mammary gland,
pancreas, pituitary, prostate (ventral), salivary gland,
seminal vesicle, skin, spleen, stomach, thyroid, tongue,
trachea, urethra, ureters, urinary bladder, uterus (cervix and
vagina), tissue masses and gross lesions.

Results and discussion

Results of examinations

Details on results:

Citation from secondary source:
All animals survived the duration of treatment. Clinical signs and ophthalmoscopic examinations did not reveal any abnormalities considered to be treatment-related. An initial decrease in weight gain was noted in the high dose group.
The majority of absolute weight, however, was within 10% of the control weights. Elevations in the mean serum glutamic pyruvic transaminase (SGPT) values were noted in the mid and high dose males and females at thirteen weeks. The albumin (ALB) values and the albumin/globulin ratios (A/G) of the high dose males also were greater than those of control at 13 weeks. When compared with the control, the mean absolute and relative (to body weight) adrenal weights were greater in all test substance-treated groups of females and in the mid and high dose groups of males. The absolute and relative liver weights of all test substance-treated groups of females also were elevated. No remarkable differences from control were noted in the liver weights or ratios of the test substance-treated males. Microscopic treatment-related changes were observed in tissues from rats of all test substance-treated groups necropsied at all intervals of the experiment. The treatment-associated changes were observed in the mesenteric and pulmonary lymph nodes, adrenal glands and liver. Generally, the lymph node changes were the earliest treatment-related change (i.e. following 34 days of treatment) and the only change with a notable gross manifestation. The incidence of all treatment-related microscopic changes were similar in rats of all groups necropsied after 13 weeks and 22 weeks of treatment with the test substance.
Reproductive organs were examined, meeting the requirements for SIDS/HPV reproductive screening.

Effect levels

Dose descriptor:

LOEL

Effect level:

ca. 170 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical biochemistry

histopathology: non-neoplastic

organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In the 13-week (extended to 21 weeks) dietary study, male and female Sprague-Dawley rats received quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, methyl sulfates at 0, 0.25, 0.5 and 10% in the diet (0 and approximately 170, 365, and 750 mg/kg/day ingested dose) continuously for 7 days/week for 13 (and 21) weeks. No mortality or significant body weight effects occurred. Increased organ weights of adrenals and liver were observed at all treatment levels. Microscopic evaluation revealed treatment related changes in mesenteric and pulmonary lymph nodes, adrenal glands and liver. Therefore, the LOEL was 170 mg/kg/day.