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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was initiated on May 12, 1965 and terminated on May 10, 1967
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study conducted in the sixties i.e., prior to the implementation of testing guidelines and GLP; thus, the study conduct does not meet current acceptability criteria. However, suitable basic data were given.

Data source

Referenceopen allclose all

Reference Type:
other: US EPA TSCA 8(e) submission
Title:
Unnamed
Year:
1990
Report Date:
1967
Reference Type:
publication
Title:
2-DIETHYLAMINOETHANOL CAS N°:100-37-8, SIDS Initial Assessment Report For SIAM 15
Author:
OECD SIDS
Year:
2004
Bibliographic source:
UNEP Publications

Materials and methods

Principles of method if other than guideline:
In the 2-year rat study, three groups of rats (initially consisting of 35 males and 35 females each) were fed DEAE for 24 months at dietary levels of 200, 500, or 1000 ppm.After week 47 the 1000 ppm group was gradually raised to 10,000 ppm as follows: Week 48 - 56,  1500 ppm; Week 57 - 64,  2500 ppm;Week 65 - 72,  3500 ppm; Week 73 - 80,  5000 ppm; Week 81 - 84,  7500 ppm; Week 85 - 104, 10000 ppm.
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diethylaminoethanol
- Analytical purity: According to the report, 1mL contains 0.577-0.585 g of Diethylaminoethanol or 0.758-0.766 g Diethylaminoethanol hydrochloride

Test animals

Species:
rat
Strain:
other: According to a personal communication with Charles River (Patricia A. Mirley, 24 June 2002, cited in the OECD SIDS 2004), the rats used were likely to be Sprague-Dawleys.
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River Breeding Laboratories, Inc .- Housing: individually- Diet: Purina Laboratory Chow, ad libitum- Water: water ad libitum- Acclimation period: 1 weekENVIRONMENTAL CONDITIONS- Temperature (°C): controlled within narrow limits (not further stated)- Humidity (%): controlled within narrow limits (not further stated)

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: The test compound was added to the basal diet on a weight/weight basis and thoroughly mixed.
Details on oral exposure:
The following groups were established:Group No. I (Control) 60 males and 60 females received only basal laboratory diet.Group No. II (Test Low Level) 35 males and 35 females received the basal laboratory diet to which 200 ppm of diethylaminoethanol was added.Group No. III (Test Intermediate Level) 35 males and 35 females received the basal laboratory diet to which 500 ppm of diethylaminoethanol was added.Group No. IV (Test high Level) 35 males and 35 females received the basal laboratory diet to which increasing amounts of diethylaminoethanol were added, as follows:1,000 ppm for weeks 1 through 471,500 ppm for weeks 48 through 562,500 ppm for weeks 57 through 643,500 ppm for weeks 65 through 725,000 ppm for weeks 73 through 807,500 ppm for weeks 81 through 8410,000 ppm for weeks 85 through 104The concentration of test material for each of the three groups of test animals was calculated according to the free base; however, the test substance was given as the HLC-salt.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
6 months, 12 months and 2 years
Frequency of treatment:
continuously in the food
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:200, 500, 1000 ppmBasis:other: (the high dose group was gradually increased from 1000 to 10,000 ppm)
Remarks:
Doses / Concentrations:11, 25, 50 mg/kg bw/dayBasis:other: (the high dose group was gradually increased from ca. 50 to ca. 400 mg/kg bw/day)
No. of animals per sex per dose:
For the DEAE-treated groups, 35 rats/sex were used, and in the control there were 60 rats/sex.
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes- Time schedule: A daily record of general physical appearance, gross signs of systemic toxicity and/or pharmacological effect, behavior, and mortality was maintained (6 days/week).BODY WEIGHT: Yes - Time schedule for examinations: Body weights were recorded weekly for the 1st 26 wks, and biweekly for the next 26 wks. In the 2nd year, body weights were measured every 4 weeks. FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Food consumption was recorded weekly for the 1st 26 wks, and biweekly for the next 26 wks. In the 2nd year, food consumption was measured every 4 weeks. HAEMATOLOGY: Yes - Time schedule for collection of blood: days 30, 45, 90, 180, 360, 540 and 720. - Anaesthetic used for blood collection: No data- Animals fasted: No data- How many animals: 5 rats of each sex and group- Parameters examined: Hematocrits, hemoglobin determinations and total and differential leukocyte counts were made from 5 rats of each sex and group. Complete blood counts were performed on 5 additional females from the control and high dose group on day 180, and total white cell counts were performed on 5 additional rats of each sex from all groups on day 360. CLINICAL CHEMISTRY: No dataURINALYSIS: Yes - Time schedule for collection of urine: day 30, 45, 60, 90, 180, 360, 540 and 720- Metabolism cages used for collection of urine: No data- Animals fasted: No data- Parameters examined: albumin, acetone, bilirubin, color, occult blood, sugar, pH, appearance and microscopic sediment examination
Sacrifice and pathology:
At 6 and 12 months, 5 animals/sex/group were sacrificed and complete necropsies were performed. Representative tissues from each animal were fixed in formalin. These tissues were: 3 sections of the brain, two sections each of the stomach and small intestine, one section each of the pituitary, thyroid, heart, lung, liver, spleen, kidney, adrenal, pancreas, large intestine, urinary bladder, gonads, bone marrow and any unusual lesion. Animals which died or which were moribund were taken and when post-mortem autolysis was not advanced, target tissues as well as tumors were examined histologically. All of these tissues from the control group and the high dose group were examined microscopically from the 6 and 12 month sample groups. At the end of 2 years, all surviving animals were necropsied. Ten animals/sex from controls and the high dose group were examined histologically. The gonads of all groups of the 2 year sampling were eventually examined histologically. Organ weights and organ/terminal body weights were recorded from all scheduled sacrificed animals.
Other examinations:
Organ weight and organ/ terminal body weights were recorded from all sacrificed rats (excluding sacrificed moribund animals) for brain, thyroid, heart, liver, spleen, kidneys, adrenals and gonads.

Results and discussion

Results of examinations

Histopathological findings: non-neoplastic:
effects observed, treatment-related
Details on results:
CLINICAL SIGNS AND MORTALITYNone of the treated animals displayed gross signs of substance-induced toxicity. Adverse signs occurred mainly in the last 6 months in all groups and were associated with aging (this included general poorer health and an increase in mortality). According to the report, since the incidence of mortality of the DEAE-treated groups compared favorably with the controls, DEAE did not produce any earlier or greater numbers of deaths at any dose level. Instances of anorexia were also reported in this study, but the data on individual animals was not given. BODY WEIGHT AND WEIGHT GAINIn the last 12 weeks of the study the high dose male body weight was on average 8.6 % (maximum 11%) lower than the controls.FOOD CONSUMPTION AND COMPOUND INTAKE According to the report, the animals were said to have generally had a vigorous appetite and the average weekly body weight and feed consumption values for males and females were generally comparable to controls at the corresponding interval. HAEMATOLOGYNo significant hematological changes were seen. In both sexes of the high dose group, the hematocrit and hemoglobin values were slightly decreased at the 720 day time point. URINALYSISThe results of the urine analyses throughout the 24 months of feeding showed no indications of adverse effects which could attributed to the ingestion of the test preparation.ORGAN WEIGHTSAll deviations were within the expected weight limits for the respective organs and there appeared to be no dose response relationship for these findingsGROSS PATHOLOGYAt 6 months no testicular atrophy was observed. At 12 months one case of slight testicular atrophy was grossly observed in a 200 ppm dosed male. In the 24 month samples testicular atrophy was observed in 0/34 control animals, 3/18 (17 %) animals of the 200 ppm dose group, 2/17 (12 %) animals of the 500 ppm dose group and 4/15 (27 %) animals of the 1000-10000 ppm dose group. In the high dose group, 3 cases were grossly described as slight atrophy in one testis, and this was confirmed histologically; the fourth case was not grossly observed, but the histologic description indicated that 2/3 of the testis had a "moderately severe" generalized degree of atrophy present with only Sertoli cells which remained within most of the seminiferous tubules. According to the sponsor, the lack of testicular atrophy in the controls was surprising given the historical control range of this lesion (data not available). It should be noted that this is not an unusual lesion in ageing rats (Glaister, 1986). One high dose female had gonadal atrophy, but the report considered this fortuitous. It should be emphasized that in the six month samples, the more appropriate time point for examining reproductive toxicity, no testicular effects were observed. The atrophy often occurred bilaterally. Careful histological examination of the cerebellums of the high dose animals revealed no anomalies. No other signs of toxicity were observed. Round worms were found in the colon of 2 control and 3 high dose animals.

Effect levels

Dose descriptor:
NOAEL
Effect level:
50 - 400 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Since gonadal atrophy was noted in four of ten male and one of ten female rats on the preliminary examination of the Test High Level and the gonadal tissues of the twenty control animals were found to be within normal limits, additional sections of gonads from all survivors at termination (24 months) were prepared to resolve the question of possible drug toxicity. The additional study comprised tissues from twenty four (24) males and twenty seven (27) females in the control group, eighteen (18) males and twenty one (21) females in the Test Low Level group, seventeen (17) males and twelve (12) females in the Test Intermediate Level group, and five (5) males and eight (8) females in the Test High Level group. All sections of ovary in the additional study in all groups (test and control) were within the limits of expected histological appearance.

All additional sections of testis in the control and Test High Level groups were similarly normal. Mild to moderate atrophy of the testicular tubules, with decreased cellularity and reduced to absent spermatogenesis was present in three (3) males in the Low Test Level group and two (2) males in the Intermediate Test Level group.

Applicant's summary and conclusion