Octyl laurate

Endpoint summary

Description of key information

Oral (read across): OECD 407, rat, NOAEL = 1000 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Version / remarks:

adopted in 1981

Deviations:

yes

Remarks:

lack of details on test substance; lack of urinary and ophthalmoscopic examination.

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Wilmington, MA, USA.
- Age at study initiation: 6 - 8 weeks old
- Weight at study initiation: 150 - 250 g
- Housing: group housed on hardwood chip bedding.
- Diet: rodent ration, AgWay Prolab, Waverly, NY. USA, ad libitum
- Water: municipal tap water, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-13
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
- The test material was dissolved in vehicle at the following concentrations: 0.025 g/mL, 0.075 g/mL and 0.250 g/mL.
- Dosing volume: 4 mL/kg bw, the doses were adjusted at weekly intervals to maintain a constant dose level by body weight.

VEHICLE
- Justification for use and choice of vehicle: water-insolubility
- Lot/batch no.: CSC-91-01-001VIV

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

once daily, 5 days/week

Remarks:

Doses / Concentrations:
100, 300 and 1000 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The three dose levels were employed based on the known toxicity of the test material.

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION: Yes
- Time schedule for examinations: weekly

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to study initiation and prior to the terminal sacrifice
- Anaesthetic used for blood collection: Yes, carbon dioxide
- Animals fasted: No data
- How many animals: all animals
- Parameters checked: erythrocyte count (RBC), hemoglobin (Hgb), hematocrit (Hct), platelet count (PT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin conc. (MCHC), mean corpuscular volume (MCV), white blood cell (WBC) differential

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: prior to study initiation and prior to the terminal sacrifice
- Animals fasted: No data
- How many animals: all animals
- Parameters checked: albumin, glucose, LDH, blood urea, ASAT, ALAT, AP, nitrogen (BUN), serum creatinine, total bilirubin, total serum protein, globulin, chloride, phosphorus, potassium, sodium, calcium

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: 1 and 6 hours after dosing and on Days 1, 7, 14, 21 and 28.
Parameters scored: Respiratory, Motor activities, Convulsion, Reflexes, Ocular signs, Cardiovascular signs, Salivation, Piloerection, Analgesia, Muscle tone, Gastrointestinal signs, Skin, Vocalization, Forelimb/Hindlimb grip strength.
The observations for neurotoxicity were made by a technician which was blind with respect to the animals´treatment. The animal to be observed was removed from the cage and placed in a designated area for the neurotoxicological observation. The observations was graded at 1 and 6 h after dosing, and on day 1, 7, 14, 21 and 28 using the following scale: 0 = normal, 1 = mild, 2 = moderate, 3 = severe


ORGAN WEIGHTS:
liver, kidney, adrenals and gonads

DETAILS:
- Hematology/Biochemistry:
Prior to the initiation of the study and prior to the terminal sacrifice, all animals were anesthetized with carbon dioxide and bled for clinical pathological evaluation of the following parameters:
* hematology: erythrocyte count, hemoglobin, hematocrit, platelet count, mean corpuscular volume, mean corpuscular hemoglobin conc., mean corpuscular hemoglobin, WBC differential
* biochemistry: albumin, blood urea, nitrogen, electrolyte (chloride, phosphorus, potassium, sodium, calcium), glucose, serum aspartate aminotransferase, serum alanine aminotransferase, serum creatinine, total bilirubin, total serum protein, globulin, LDH, cholesterol, alkaline phosphatase.

- Procedures during treatment:
Body weight and food consumption were measured weekly. Daily clinical observations included all clinical signs.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, all animals. (Examination of the external surface, all orifices, cranial, thoracic and abdominal cavities)
HISTOPATHOLOGY: Yes, from animals of the control and highest dose group
The following organs were examined histopathologically: adrenal glands, heart, lung, liver, kidney, spleen, ovaries and testes.

Clinical signs:

no effects observed

Description (incidence and severity):

No clinical signs were observed during the course of the study in either the control or test animals.

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

All animals showed the expected gain in body weigh during the course of the study.

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

No treatment-related significant differences were observed. The observed changes had no dose-response.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

No treatment-related differences between control and tested groups were observed.

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Description (incidence and severity):

No signs of neurotoxicity were observed during the course of the study.

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

The relative kidney and liver weights were significantly different in male animals treated with 100 mg/kg compared with control animals.
As the other organs from groups with higher doses showed no significant differences, no dose-response relation occurred. Therefore these changes can be regarded as non-treatment related.

Gross pathological findings:

no effects observed

Description (incidence and severity):

There were no abnormal signs observed during the gross necropsy of any animal.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No treatment-related effects were observed in the analysed organs.

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Key result

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects on: clinical manifestation, neurotoxicity, on various blood parameters (hematology and clinical chemistry), necropsy, organ weights, body weights, food consumption and histopathological findings.

Key result

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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

Additional information

Analogue justification

There are no data on the repeated dose toxicity of Octyl laurate (CAS 5303-24-2). The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Repeated dose toxicity, oral, subacute

CAS 135800-37-2

A 28-day oral repeated dose toxicity study was performed according to OECD 407, with Fatty acids, C8-12, 2-ethylhexyl esters (key study, 1991). Five Wistar rats/sex/dose were administered 100, 300 and 1000 mg/kg bw/day by gavage, for 28 days (treatment 5 days/week). There was no treatment-related mortality and no clinical signs were observed during the study period. No significant differences in body weight, body weight gain, food consumption, haematology results and clinical chemistry results were noted between the control group and treatment groups. The relative kidney and liver weights were significantly different in male animals treated with 100 mg/kg bw/day compared with control animals. As the other organs from groups with higher doses showed no significant differences, no dose-response relation occurred. Therefore these changes were not considered to be treatment related. No treatment-related effects were observed during the macroscopic and microscopic examinations. Based on the lack of toxicologically relevant effects up to and including the highest dose level, the NOAEL is considered to be 1000 mg/kg bw/day.

 

 

CAS 22393-85-7

A combined repeated dose toxicity and reproduction/developmental toxicity screening study (according to OECD Guideline 422 and in compliance with GLP) was performed (supporting study, 2014). 10 rats/sex/dose were administered 0, 100, 300 and 1000 mg/kg bw/day Tetradecyl oleate once daily for 28-29 days (males) and up to 54 days (females) via gavage. The application started two weeks before mating on test day one and ended on the day of or one day before sacrifice. Day of sacrifice was on test day 29 or 30 for the male rats and on lactation day 3 or shortly thereafter for the female rats. There was no mortality during the study period. No toxicologically relevant clinical signs were observed. The body weight, body weight gain and food consumption was comparable between the control and treatment groups. There were no toxicologically relevant effects on organ weights. The statistically significant differences in haematological parameters between control and treated animals (erythrocytes, mean corpuscular haemoglobin and leucocytes in males, haemoglobin, haematocrit and platelets in females) were of low magnitude and/or not dose-related, and therefore considered incidental. Statistically significant fluctuations of some biochemical parameters, compared with the control groups, were recorded in both sexes. An increase in glucose levels in males administered 100 and 1000 mg/kg bw/day (48% for both doses), and an increase in urea in males receiving 100 mg/kg bw/day (19%) was observed. In females in the 300 mg/kg bw/day group, an increase in aspartate aminotransferase level (35%) was noted, while for females administered 1000 mg/kg bw/day, a decrease in bilirubin levels (81%) and an increase in potassium levels (10%) was observed. Due to the lack of dose- and/or sex-consistency, and due to the absence of other relevant findings, these changes are not considered to be toxicologically relevant. There was no significant difference between control and treatment groups during the observational and neurological screenings. The macroscopic inspection at autopsy and subsequent histopathological examination did not reveal any treatment-related changes. The NOAEL for systemic toxicity was considered to be 1000 mg/kg bw/day.

 

Overall conclusion for repeated dose toxicity

The data for the read-across analogue substance showed that no effects were observed up to and including the recommended limit values. Therefore, as the available data did not identify any hazard for repeated dose toxicity, Octyl laurate (CAS 5303-24-2) is not considered to be hazardous following repeated exposure.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Octyl laurate (CAS 5303-24-2), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.