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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From June 1965 to September 1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across study hence maximum reliability rating of 2 assigned according to ECHA guidance, although study was conducted is well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1965

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A study was conducted to evaluate the subchronic oral toxicity of the test material in rats. Test animals were administered daily dietary levels of the test material at 0, 0.1, 0.5, 1and 2 % for 90 d. The animals were daily observed for clinical signs, weekly once body weights were recorded and hematological, clinical chemistry and urine examinations were carried out at termination. Gross examination and histopathological examinations were also performed.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Lauric diethanolamide
- Analytical purity: 92.36 %
- Impurities (identity and concentrations): Free diethanolamine (5.6 %); free alkali, as KOH (0.08 %); petroleum ether extractive (1.96 %)

Test animals

Species:
rat
Strain:
other: Carworth Farm E
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Age at study initiation: Weanlings
- Housing: Five animals per cage
- Diet: Powdered Spillers Small Laboratory Animal Diet, ad libitum
- Water: Water, ad libitum

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Not reported
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Not applicable
Duration of treatment / exposure:
90 d
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.1, 0.5, 1 and 2 %
Basis:
nominal in diet
No. of animals per sex per dose:
15
Control animals:
yes, plain diet
Details on study design:
Not reported
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: Day 0 and weekly once thereafter


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Time schedule for examinations: Day 0 and weekly once thereafter



HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the study
- Parameters checked in table [No.?]: Total erythrocyte count, hematocrit, hemoglobin, reticulocyte count, total and differential leucocyte counts


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the end of the study
- Parameters checked in table [No.?] were examined: Liver and kidney function tests and levels of serum glutamic-oxaloncetic and glutamic-pyruvic transaminases and of blood urea checked


URINALYSIS: Yes
- Time schedule for collection of urine: At the end of the study
- Parameters checked in table [No.?] were examined: Urine was examined for colour, pH, microscopic constituents, protein, reducing substances, bile salts and blood and activity of glutamic-oxaloacetic transaminase. Volume and the specific gravity of the urine excreted were measured during a 6 h period of water deprivation and during 4 h period commencing 16 h after a water load of 25 mL/kg.



OTHER: At autopsy, the absolute and relative organ weight of the brain, heart, liver, kidneys, adrenals and gonads were recorded.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes (At autopsy, the gross appearance of the brain, heart, liver, kidneys, adrenals and gonads were recorded)
HISTOPATHOLOGY: Yes (Paraffin wax sections of brain, heart, liver, kidneys, adrenals and gonads together with a wide range of other organs were stained with haematoxylin and eosin for histological examination, smears of femoral marrow were stained by the May Grunwald-Giemsa method)
Other examinations:
Palatability test: Pairs of male rats were allowed access to stock diet and to diet containing either one of the four dietary test levels of test material. The consumption of both diets was recorded for a period of 8 d.
Statistics:
Not reported

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
effects observed, treatment-related
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY: In general rats remained in good health apart from 2 males on 1 % test material which were killed on Days 23 and 58 because of weight loss and respiratory distress.


BODY WEIGHT AND WEIGHT GAIN: Reduced body weight gain was observed from 0.5 % onwards.


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Food intake was reduced at all dietary levels except the lowest level of 0.1 %.


HAEMATOLOGY: Reductions in hemoglobin levels, hematocrit values and red cell counts in females at 1 and 2 % levels but these effects were much less pronounced in males.


CLINICAL CHEMISTRY: Serum levels of glutamic-oxaloacetic transaminases were significantly elevated at 0.5 % and above in females, but only at 0.5 % level in males.


URINALYSIS: Proteinurea was comparable in test and control groups. Tests for blood, bile salts and reducing substances were negative in all groups. Level of Glutamic-oxaloacetic transaminase were significantly elevated at dietary levels of 0.5 % and above in females but only at the 0.5 % level in males. No significant effect was seen in Glutamic-pyruvic transaminase level at all dietary levels.



ORGAN WEIGHTS: The principal organ weight changes were increases in the relative kidney weight in all test groups except at 0.1 % in females and at 0.1 and 0.5 % in males and increases in relative liver weight in female on the two highest levels.


GROSS PATHOLOGY: No significant findings were observed.


HISTOPATHOLOGY: Examination of the femoral marrow smears showed no deviation from normality. There were no adverse histopathological findings in any organs.


OTHER FINDINGS: In the palatability test, exclusive preference was shown to the control diet, virtually no test diet being consumed at any of the dietary levels incorporated. This observation suggests that toxic anorexia was not the cause of reduced food intake.

Effect levels

Dose descriptor:
NOEL
Effect level:
50 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: Overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Under the conditions of the test, the subchronic no-effect level (NOEL) of the test material in rats was considered to be 0.1 % in the diet, equivalent to 50 mg/kg bw/d.

Executive summary:

A study was conducted to evaluate the subchronic oral toxicity of lauric acid diethanolamine condensate, (LDEA, CAS No.120-40-1)in rats.

Test animals were administered daily dietary levels of the test material at 0, 0.1, 0.5, 1and 2% for 90 d. The animals were daily observed for clinical signs, weekly once body weights were recorded and hematological, clinical chemistry and urine examinations were carried out at termination. Gross examination and histopathological examinations were also performed.

No adverse effect on the appearance or condition of the animals was observed. Growth retardation was associated with diminished food intake from the dose level of 0.5%. Food refusal was demonstrably due to an effect of the test material on palatability of the diet. Terminal hematological examination revealed a reduction in the hemoglobin level, haematocrit and red cell count at 1 and 2% levels in females but less pronounced effects were seen in males. Serum levels of glutamic-oxaloacetic transaminase were elevated at 0.5% and above in females but only at 0.5 % in males. No untoward effect was observed in the renal function tests. The principal organ weight changes were: increases in the relative kidney weight in all test groups except at 0.1% in females and at 0.1 and 0.5% in males; and increases in the relative liver weight in females on the two highest levels. The types and incidence of histological lesions were comparable in control and test groups.

Under the conditions of the test, the subchronic No-Observed Effect Level (NOEL) of lauric acid diethanolamine condensate, (LDEA, CAS No.120-40-1)in rats was considered to be 0.1 % in the diet, equivalent to 50 mg/kg bw/d.