Reaction mass of 2-hydroxyethyl oleate, oleic acid, and 2-hydroxyethyl palmitate

Endpoint summary

Description of key information

In a reliable in vivo study male and female rats were administered an analogue substance via oral gavage for 90 days at the approximate dosages of 100, 300 and 1000 mg/kg/day. No mortality occurred and no treatment-related clinical signs were observed during the study. No signs of toxic effects, which could be considered adverse, were seen during the study. No changes of toxicological relevance were observed in body weight and food consumption. In females from the 100 mg/kg bw/day group only the relative organ weights of kidney and brain were slightly increased. No lesions were recorded at ophthalmological examination. No treatment-related findings were reported at post mortem macroscopic observations and histopathological examination. In conclusion, no treatment-related changes, which could be considered adverse, were observed in male and female rats following dosing with the substance, when administered via oral gavage for 90 consecutive days at the approximate dosages of 100, 300 and 1000 mg/kg/day. Therefore, it can be concluded that the No Observed Adverse Effect Level (NOAEL) for this study was 1000 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Read-across from a K1 study therefore K2 is the maximum Klimisch score assignable

Justification for type of information:

A read-across justification is provided in section 13 of the IUCLID file.

Reason / purpose for cross-reference:

read-across source

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Züchter Winkelmann, Borchen, Germany
- Age at study initiation: approx. 4 weeks
- Weight at study initiation: 46 - 58 g (males) and 46 - 57 g (females)
- Housing: 2-3 animals in Makrolon-cages Typ M 5 (EBECO, Castrop-Rauxel, Germany)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 38-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
- Daily, immediately before dosing

VEHICLE
- Justification for use and choice of vehicle (if other than water): solubility of test substance
- Concentration in vehicle: 20, 60 and 200 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg bw/day

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily, 5 days per week

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

10
5 (additional in high dose group and control group)

Control animals:

yes, concurrent vehicle

Details on study design:

- Rationale for selecting satellite groups: high dose and control groups
- Post-exposure recovery period in satellite groups: 34 days

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily during acclimation period, twice daily during application period and daily on weekends and holidays.
- Cage side observations checked: mortality, intoxication symptoms.

BODY WEIGHT: Yes, as mean body weight.
- Time schedule for examinations: at study initiation, once during acclimatisation period, daily during the application period.

FOOD CONSUMPTION AND WATER CONSUMPTION: Yes, as g/animal/week.
- Time schedule for examinations: weekly.

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: day before sacrifice.
- Dose groups that were examined: high dose and control satellite groups.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 6 weeks application and at study termination.
- How many animals: all.
- Parameters checked: erythrocyte count, hematocrit, mean cell volume, hemoglobin, leucocyte count, thrombocyte count, differential blood count.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after 6 weeks application and at study termination.
- How many animals: all
- Parameters checked: gamma glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatise, sodium, potassium, glucose, urea, protein, calcium, creatinine, cholesterol, chloride, bilirubin.

OTHER: organ weights: absolute and relative organ weights of brain, testes, heart, liver, spleen, adrenal gland, kidney, thymus.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, whole body, especially eyes, skin, abdomen, chest and skull.
HISTOPATHOLOGY: Yes, aorta thoracica, eye, colon, proventriculus, small intestine, cerebrum, urinary bladder, skin, heart, testes, hypophysis, cerebellum, liver, lung, trachea, axillary lymphnodes, mesentery lymphnodes, spleen, epididymis, adrenal gland, peripheral nerve, kidney, ovary, pancreas, prostate, vesicula seminalis, thyroid gland, salivary gland, esophagus, skeletal muscles, thymus, uterus, tongue, rumen.

Statistics:

Student's t-test, steel test

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

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

non-adverse effects

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
No mortalities occured.

BODY WEIGHT AND WEIGHT GAIN
Normal weight gain in all groups.

FOOD CONSUMPTION AND WATER CONSUMPTION
No abnormalities.

OPHTHALMOSCOPIC EXAMINATION
No damage.

HAEMATOLOGY
No abnormalities.

CLINICAL CHEMISTRY
No abnormalities.

ORGAN WEIGHTS
In females from the 100 mg/kg bw/day group only the relative organ weights of kidney and brain were slightly increased.

GROSS PATHOLOGY
No treatment related findings.

HISTOPATHOLOGY: NON-NEOPLASTIC
No treatment related findings.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
No treatment related findings.

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects on: clinical signs; mortality; body weight; food consumption; ophthalmoscopic examination; haematology; clinical chemistry; gross pathology; organ weights; histopathology

Critical effects observed:

not specified

The oral administration of the test substance for 90 days, five days per week led to no significant adverse effects in male and female rats. Therefore the NOAEL for the test substance is set to 1000 mg/kg bw/day.

Conclusions:

The oral administration of the substance for 90 days, five days per week led to no significant adverse effects in male and female rats. Therefore the NOAEL for the substance is set to 1000 mg/kg bw/day.

Executive summary:

Male and female rats were administered the substance via oral gavage for 90 days at the approximate dosages of 100, 300 and 1000 mg/kg/day.No mortality occurred and no treatment-related clinical signs were observed during the study. No signs of toxic effects, which could be considered adverse, were seen during the study. No changes of toxicological relevance were observed in body weight and food consumption.In females from the 100 mg/kg bw/day group only the relative organ weights of kidney and brain were slightly increased.No lesions were recorded at ophthalmological examination.No treatment-related findings were reported at post mortem macroscopic observations and histopathological examination.In conclusion, no treatment-related changes, which could be considered adverse, were observed in male and female rats following dosing with the substance, when administered via oral gavage for 90 consecutive days at the approximate dosages of 100, 300 and 1000 mg/kg/day.Therefore, it can be concluded that the No Observed Adverse Effect Level (NOAEL) for this study was 1000 mg/kg/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Sufficient to address requirements.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the findings of a reliable 90 day sub-chronic toxicity study conducted on an analogue substance, classification of the substance is not justified.