Palmidrol

Repeated dose toxicity: oral

Administrative data

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:

comparable to guideline study

Justification for type of information:

This 14 d study, intended to be a dose-ranging study to identify doses to be used in a subsequent 90 d study.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

duration: 14 d

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Palmidrol

EC Number:

208-867-9

EC Name:

Palmidrol

Cas Number:

544-31-0

Molecular formula:

C18H37NO2

IUPAC Name:

N-(2-hydroxyethyl)hexadecanamide

Test material form:

solid

Remarks:

particle size: 0.5–10 μm

Details on test material:

manufactured by Epitech Group Srl, Milano Italy, supplied by Prismic

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Sprague-Dawley rats (Vivo Bio Tech Ltd), age: 6–7 weeks

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: water with Tween 80 (0.5 % w/v) and carboxymethyl cellulose (1 % w/v)

Details on oral exposure:

Preliminary tests found that the test substance was suitable for oral gavage by suspension in water with Tween 80 (0.5 % w/v) as a surfactant and carboxymethyl cellulose (1 % w/v) as a suspending agent.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Analyses performed to verify the concentrations of the test substance in dosing formulations in the 90-day study showed that they were within an acceptable range compared to their respective nominal concentrations.

Duration of treatment / exposure:

14 d

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

five of each sex

Control animals:

yes

Details on study design:

The following observations and examinations were performed: mortality and clinical signs – daily, body weight and food consumption – weekly. Additionally samples for hematology and clinical chemistry analysis were taken just prior to sacrifice, and gross necropsy was performed, recording any gross pathological observations and organ weights.

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

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not specified

Effect levels

Key result

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Under the study conditions, the NOEL from this study was >1000 mg/kg bw/day.

Executive summary:

A study was conducted to determine repeated dose toxicity of the test substance according to a design based on OECD Guideline 407. This 14 d study intended to identify the dose-range to be used in a subsequent 90 d study. Preliminary tests found that the test substance was suitable for oral gavage by suspension in water with Tween 80 (0.5% w/v) as a surfactant and carboxymethyl cellulose (1% w/v) as a suspending agent. Ten Sprague-Dawley rats, five of each sex, were dosed with a vehicle control and with the test substance at 100, 300, and 1000 mg/kg bw/day daily through duration of the study. Observations for mortality and clinical signs were made daily and of body weight and food consumption weekly. Additionally samples for hematology and clinical chemistry analysis were taken just prior to sacrifice, and gross pathology was performed. Analyses performed to verify the concentrations of the test substance in dosing formulations in the 90-day study showed that they were within an acceptable range compared to their respective nominal concentrations. No incidence of clinical signs or death was found following 14 days of treatment with the test substance at 0, 100, 300, or 1000 mg/kg bw/day. Furthermore, no adverse effects were observed on body weight gain, food consumption, hematological parameters, clinical chemistry, gross pathology, or on absolute or relative organ weights. Under the study conditions, the NOEL from this study was >1000 mg/kg bw/day (Nestmann, 2017).