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Administrative data

Endpoint:
short-term repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The original publication is in Japanese, with abstract and tables written in English; an English translation of the paper exists. The reported data were scientifically acceptable.

Data source

Reference
Reference Type:
publication
Title:
Acute and subacute toxicity studies and local irritation study of glutaraldehyde.
Author:
Uemitsu N, Kawasaki H, Furuhashi T, Miyoshi K, Ohtaka T, Nomura A, Hasegawa T, Shimizu Y, Nakazawa M
Year:
1976
Bibliographic source:
Oyo Yakuri 12(l): 11-32, (Japanese publication & English translation)

Materials and methods

GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Glutaral
EC Number:
203-856-5
EC Name:
Glutaral
Cas Number:
111-30-8
Molecular formula:
C5H8O2
IUPAC Name:
glutaraldehyde
Test material form:
liquid
Specific details on test material used for the study:
Glutaraldehyde 25% aq. solution, from Johnson and Johnson Far East Inc.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
The males had an initial mean body weight of about 210 g/animal
The females had an initial mean body weight of about 140 g/animal

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
physiological saline
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
35 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
1 mg/kg bw/day
Dose / conc.:
5 mg/kg bw/day
Dose / conc.:
25 mg/kg bw/day
Dose / conc.:
125 mg/kg bw/day
No. of animals per sex per dose:
Each group consisted of 10 animals/sex.
Control animals:
yes, concurrent no treatment
Details on study design:
The experimental series consisted of 5 groups, four treated groups and one control group; the control group received physiological saline.
Each group consisted of 10 animals/sex.

Examinations

Observations and examinations performed and frequency:
The animals were regularly observed for mortality and clinical symptoms of toxicity.
Body weight changes and food consumption were recorded.
A series of hematological parameters including red and white blood cells counts, hematocrit, hemoglobin and differential white blood cells counts was
examined, as well as a series of clinical-chemical parameters including GOT, GPT, ALP, LDH, Total protein, cholesterol, glucose, N-urea, bilirubin, albumin, Na, K, Cl.
Urinalysis also was performed.
Sacrifice and pathology:
At the end of the experiment the animals were sacrificed for the purpose of necropsy.
They were subjected to gross pathology and the absolute and relative weights of a series of organs including pituitary, brain, thyroid, thymus, lung, heart, liver, kidney, adrenals, spleen, testes, epididymis and prostate were determined.
- A series of organs/tissues was fixed with formaline and sections were prepared and stained with hematoxylin/eosin for further histopathological examinations.

Results and discussion

Results of examinations

Mortality:
no mortality observed
Description (incidence):
- No treatment-related mortality was reported.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
- A decrease in body weight gain was reported for the males of the 125 mg/kg bw group; in fact at the end of the experimental period, the treated males of the 125 mg/kg bw group hat a mean body weight of ca. 310 g /animal versus ca. 375 g for the control males (initial body weight for all males about 210 g/animal). The males of the 25 mg/kg bw group also showed a slight decrease in body weight gain when compared to controls, reaching about 340 g/animal at the end of the experiment. Body weight gain of the treated females was inconspicuous and within the range of controls (ca. 220 - 230 g/animal after 35 days, versus ca. 140 g/animal at test starting).
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
- Food consumption of the 125 mg/kg bw males was reduced when compared to controls; in fact, over a period ranging from day 7 of treatment to day 14, food consumption of the treated rats decreased from about 22 g/day to ca. 17 g/day (reduction of ca. 23%). Starting from day 21 of treatment, a slight increase in mean food consumption was noticed (ca.19 g/day towards the end of the treatment period). Food consumption for the treated females was within control range.
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
- At both test doses of 25 and 125 mg/kg bw, the animals showed signs of inflammation and necrosis at the injection sites. The inflammation was accompanied by changes in following hematological parameters:
- Increase in white blood cells count: males: 127 +/-23 *10 E+2 cells/mm3 at 25 mg/kg bw and 181 +/-55 *10 E+2 cells/mm3 at 125 mg/kg bw, versus 91 +/-18 *10 E+2 cells/mm3 in control; females: 155 +/-37 *10 E+2 cells/mm3 at 25 mg/kg bw and 176 +/-32 *10 E+2 cells/mm3 at 125 mg/kg bw, versus 99 +/-13 *10 E+2 cells/mm3 in control.
- Decrease in hematocrit: males: 38.2% +/-1.7 at 25 mg/kg bw and 36.9% +/- 2.2 at 125 mg/kg bw, versus 47.2% +/- 1.6 in control; females: 39.5% +/-2.3 at 25 mg/kg bw and 37.2% +/- 0.9 at 125 mg/kg bw, versus 44.5% +/- 1.4 in control.
- Decrease in hemoglobin: males: 12.8 +/- 0.6 g/dl at 25 mg/kg bw and 12.1 +/- 0.9 g/dl at 125 mg/kg bw, versus 15.3 +/- 0.4 g/dl in control; females: 11.7 +/- 0.7 g/dl at 25 mg/kg bw and 11.1 +/- 0.3 g/dl at 125 mg/kg bw, versus 14.8 +/- 0.6 g/dl in control.
- Decrease in lymphocytes: males: 75.8% +/- 7.8 at 25 mg/kg bw and 64.6% +/- 10.3 at 125 mg/kg bw, versus 89.1% +/- 4.6 in control; females: 74.1% +/- 11.2 at 25 mg/kg bw and 76.8% +/- 9.8 at 125 mg/kg bw, versus 89.1% +/- 4.5 in control.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
- Excepted for an increase in serum N-urea (125 mg/kg bw females: 26.5 mg/dl +/- 5.9 versus 17.8 mg/dl +/- 4.6 for control females) the considered clinical-chemical were inconspicuous.
Urinalysis findings:
no effects observed
Description (incidence and severity):
The urinary parameters also were inconspicuous, excepted for an increase in total protein content.
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
- Organ weights were inconspicuous.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
- Necropsy and histopathological examination revealed hypertrophy of white pulps in the spleen, thymus atrophy and atrophy of the glandular epithelium of the prostate; the renal tubuli in the kidneys showed degeneration.
- Excepted for slight cell infiltrations and edema at the injection sites, the animals of the lowest test dose (1 mg/kg bw) showed no effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion