Alcohols, C6-24, distn. residues

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Assessment carried out with ToxRTool (Schneider K. et al. "ToxRTool", a new tool to assess the reliability of toxicological data. Toxicol Lett. 2009 Sep 10;189(2):138-44.)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

precursor to 408 designed as limit test

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C16-18, distn. residues

EC Number:

271-645-5

EC Name:

Alcohols, C16-18, distn. residues

Cas Number:

68603-17-8

IUPAC Name:

68603-17-8

Details on test material:

- Name of test material (as cited in study report): residues from ocenol destillation (Pernil RU )
- Physical state: liquid (oily)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mus-ratus, Brunntal, Germany
- Age at study initiation: 23-30 days
- Weight at study initiation: 130g (males) / 118g (females)
- Housing: 2-3 males per cage; 5 females per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 50 +/- 5
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

12 weeks

Frequency of treatment:

5 times per week

Doses / concentrations

Remarks:

Doses / Concentrations:
250 mg/kg bodyweight per day
Basis:
actual ingested

No. of animals per sex per dose:

per dose: 40 rats (20 males and 20 females) + additional 20 (10 males and 10 females) as substitutes in case of wrong administration

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Positive control:

not required

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

HAEMATOLOGY: Yes
- Time schedule for collection of blood: start and end of study
- How many animals: all

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:start and end of study
- How many animals: all

URINALYSIS: Yes
- Time schedule for collection of urine:start and end of study
- How many animals: all

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

no effects observed

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

BODY WEIGHT AND WEIGHT GAIN:
In week 11, the females showed a sligt decrease in body weight, which was reversed the week after.


HAEMATOLOGY
Significantly increased hematocrit and increased mean cell volume in peripheral blood, which is not unusual for rats of that age.

CLINICAL CHEMISTRY
Females:
- glutamate-pyruvate-transaminase increased, but not pathologically
- glutamate-oxalacetate increased with 5 pathological cases
- alkaline phosphatate (AP) increased: incidental finding
- serum-sodium significantly decreased
Males:
AP incresed: not pathological, but random effect


URINALYSIS
Incidental findings, not considered to be treatment-related


ORGAN WEIGHTS
Male:
- increase absolute thyroid-weights with no histological findings


HISTOPATHOLOGY: NON-NEOPLASTIC
In both species and in tretaed and control group, comparable slight hepacytolysis with accumulation of yellow pigment in hepatocytes (not substance related).
Two findings in the large intestine were not substance-related, but hinted a ordinary causes, such as parasites.




OTHER FINDINGS

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 250 mg/kg bw/day (nominal)

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In a 90-day rat study similar to OECD test guideline 408 (oral gavage), no treatment-related adverse systemic effects of the test substance were observed. The NOAEL was determined to be 250 mg/kg bodyweight/day.

Executive summary:

The subchronic toxicity of the test substance was investigated in a 90-day study similar to OECD test guideline 408. The test substance dose of 250 mg/kg bodyweight was applied orally by gavage using CMC as vehilce five times per week to Wistar rats of both sexes.

No treatment-related adverse systemic effects were observed with any parameter investigated

(clinical signs and mortality, body weight gain, haematology, biochemistry, urinanalysis and (histo-)pathology). Therefore, the NOAEL was determined to be 250 mg/kg bodyweight/day.