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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
May-July 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1a: Guideline study (GLP)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Version / remarks:
(July 1995)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Constituent 1
Reference substance name:
2,2',2''-Nitrilotriethanol, propoxylated
EC Number:
500-094-8
EC Name:
2,2',2''-Nitrilotriethanol, propoxylated
Cas Number:
37208-53-0
Constituent 2
Reference substance name:
2,2',2''-Nitriolotriethanol, propoxylated
IUPAC Name:
2,2',2''-Nitriolotriethanol, propoxylated
Details on test material:
Molecular Mass: (average Mn = 340 g/mol)
Batch #: 197
Yellowish viscous Fluid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals were supplied by 'Harlan GmbH', Borchen, Germany and were about 4 weeks old. Males had an initial weight of 97 (83-114)g and females of 101 (95-108).
Animals were housed individually in Makrolon(R) cages Type II on wood granules. All animals or the study were kept in the same room with no other animals from other studies and in an 20 Pa overpressure environment at 22°C, 55 +/-5% relative humidity and a 12 hour light/dark cycle and low-noise music.
Diet was standard diet "Provimi Kliva 3883.0.15" pellets supplied by Provimi Kliva SA, Kaiseraugst, Switzerland ad libitum. Water was provided ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
vehicle: demineralized water
administration volume: 10 ml/kg bw
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
not applicable
Duration of treatment / exposure:
31 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300, 1000 mg/kg/body weight
Basis:
actual ingested
No. of animals per sex per dose:
5 males + 5 females
Control animals:
yes, concurrent vehicle
Details on study design:
5 male and 5 female Wistar rats/dose and control group
ADMINISTRATION/EXPOSURE:
vehicle: demineralized water
administration volume: 10 ml/kg bw
Positive control:
not applicable

Examinations

Observations and examinations performed and frequency:
CLINICAL OBSERVATION AND FREQUENCY:

Inspection of Animals:
for morbidity and mortality: Twice daily, once daily on weekends and public holidays
general clinical examinations (in cage): Daily
detailed clinical examinations: Weekly
open field observation (OFO): Once before start and once weekly thereafter
Ophthalmology: At study begin: All rats.
At termination: Control and high dose
Functional Observational Battery: Day25
Motor Activity: Day 29
Determination of body weight(s): Daily
food consumption: Weekly
water consumption: Weekly

CLINICAL PATHOLOGY at the end of study:

HEMATOLOGY:
Leukocytes, Erythrocytes, Hemoglobin, Hematocrit, Reticulocytes, Differential blood count, Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), HQUICK, Platelets

CLINICAL CHEMISTRY:
Alanine aminotransferase, Alkaline phosphatase,Aspartate aminotransferase,Gamma glutamyl transferase, Glutamate dehydrogenase, Lactate dehydrogenase, Creatin kinase, Albumin, Cholesterol, Creatinine, Glucose, Total protein, Urea, Potassium, Sodium, Calcium, Chloride, Inorganic Phosphate
Sacrifice and pathology:
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):

- Gross Pathology:
Fixed organs: Adrenals, aorta, brain (cerebrum, cerebellum, ponslmedulla), epididymides, esophagus, eyes, eyelids, extraorbital lachrymal glands, femur, harderian glands, head (with nasal and paranasal cavities), heart, intestine (duodenum, jejunum, ileum, cecum, colon, rectum and remaining intestine), kidneys, larynx, liver, lymph nodes (mandibular, bronchial/hilus, and mesenteric), lung, mamma, optical nerves, ovaries, oviducts, pancreas, pharynx, pituitary, prostate, salivary glands, sciatic nerve, seminal vesicles (incl. coagulating glands), skeletal muscle (thigh), skin (mammary and muzzle), spinal cord (cervical, thoracic, lumbar), spleen, sternum, stomach (forestomach and glandular stomach), testes, thymus, thyroids (including parathyroid glands), tongue, trachea, ureter, urethra, urinary bladder, uterus with uterine cervix, vagina, Zymbal’s glands and all organs or tissues with macroscopic findings.

- Microscopic: Adrenals, aorta, brain (cerebrum, cerebellum, ponslmedulla), epididymides, esophagus, femur, heart, intestine (duodenum, jejunum, ileum, cecum, colon, rectum and remaining intestine), kidneys, liver, lung, lymph nodes, ovaries, oviducts, pancreas, pituitary, prostate, salivary glands, sciatic nerve, seminal vesicles (incl. coagulating glands), skeletal muscle (thigh), skin (mammary and muzzle), spinal cord (cervical, thoracic, lumbar), spleen, sternum, stomach (forestomach and glandular stomach), testes, thymus, thyroids (including parathyroid glands), trachea, urinary bladder, uterus with uterine cervix, and all organs or tissues with macroscopic findings. Slides were prepared from the first five animals of all groups and evaluated from the control and the high concentration group.


ORGAN Weights:
Adrenals, brain, epididymides, heart, kidneys, Liver, Ovaries, Spleen, Testes, Thymus, uterus

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Clinical observations nor behavioral investigations of the animals revealed no treatment-related findings. Furthermore, survival, body weight and food consumption were also not effected by the treatment. Slight changes were observed in blood counts, clinical laboratory parameters and histopathology, but these were all considered to be adaptive with limited toxicological relevance.

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: not applicable

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL > 1000 mg/kg bw/day
Executive summary:

2,2',2''-Nitrilotriethanol, propoxylated was administered orally by gavage to 5 male and 5 female Wistar rats per dose group, in doses of 0, 100, 300 and 1000 mg/kg bw for a period of 31 days. Clinical observations nor behavioral investigations of the animals revealed no treatment-related findings. Furthermore, survival, body weight and food consumption were also not effected by the treatment. Slight changes were observed in blood counts, clinical laboratory parameters and histopathology, but these were all considered to be adaptive with limited toxicological relevance.