Alcohols, C6-8, ethoxylated

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well conducted and documented dose-range-finder study which was performed following OECD guideline 407 testing principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

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:

yes

Remarks:

Dose-range-finder with limited parameters investigated

Principles of method if other than guideline:

Screening study for establishing dose levels for subsequent studies and for comparing general toxicity profiles of ethoxylated alcohols

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C6-C8-(even numbered, linear)-ethoxylated (<2,5 EO)

EC Number:

800-182-9

Cas Number:

1426148-68-6

Molecular formula:

R-O-R' , whereas R=C6-8-(even numbered, linear, saturated)-alkyl and R'=H or xEO wheras x=1-12, mean=2,3

IUPAC Name:

Alcohols, C6-C8-(even numbered, linear)-ethoxylated (<2,5 EO)

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 238 - 258 (males), 155 - 173 (females)
- Fasting period before study: overnight
- Housing: individually in IVC cages, type III H
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: adequate period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): min 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Test item was prepared freshly on each administration day before the administration

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 62,5. 250, 1000 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

3 male and 3 female animals per group

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: days 1, 7 and 14

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at terminal sacrifice
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, overnight
- How many animals: all animals
- Parameters examined: haematocrit, haemoglobin content, red blood cell count, platelet count, white blood cells

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at terminal sacrifice
- Animals fasted: Yes, overnight
- How many animals: all animals
- Parameters examined: ALAT, ASAT, AP, creatinine, total protein, albumin, urea, total cholesterol, Na, K

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: Inflammatory markers (C-reactive protein, alpha-1-AGP, haptoglobin)

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: No

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

slight body weight decrease in high dose animals

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:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

decrease in WBC in high dose males

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

ASAT and ALAT slightly increased in Md and HD animals, alkaline phosphatase decreased in MD and HD animals, creatinine decreased in female HD animals

Urinalysis findings:

not examined

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:

not examined

Histopathological findings: neoplastic:

not examined

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Repeated administration via gavage of the submission substance for 14 consecutive days to rats revealed no mortalities but minor toxicological findings in animals of the 250 mg/kg and 1000 mg/kg dose groups.

Executive summary:

The submission substance was orally administered in graduated doses of 0, 62.5, 250 and 1000 mg/kg body weight per day to 3 groups of 3 male and 3 female Wistar rats each by oral gavage. One group receiving the vehicle sterile water served as control. The volume of application was 5 mL/kg body weight and the animals were dosed 7 days per week for a period of 14 days. All surviving animals were sacrificed on day 15 and were subjected to a detailed gross necropsy. All found dead animals, moribund and intercurrently sacrificed animals were also subjected to a gross necropsy. Body weight gain and food consumption were measured. Organ weights were taken from all terminally sacrificed animals.

Test item related clinical signs (i.e. piloerection, salivation, respiratory sound, moving the bedding) were observed in all high dose male and female animals. One female animal from the high dose group was found dead on day 2. The cause of the death could not be determined. Clinical signs of intoxication were not revealed throughout the study. Body weights were slightly decreased in both, male and female animals of the mid and high dose group. This corresponded with a slight decrease in food consumption in the mid and high dose animals. All group mean and individual values of haematological parameters were within the biological range except for an decrease in WBC. Clinical chemistry changes especially in high dose animals were mainly related to slight increases in ALAT and ASAT activities as well as decreases in alkaline phosphatase and creatinine. Gross pathology revealed no macroscopic findings in any of the treatment or control groups. With regard to organ weights, no treatment related effects occurred. Based on the results, it was concluded that dose levels of 62.5, 250 and 1000 mg/kg body weight may be appropriate for any subsequent 28-day repeated dose toxicity and/or reproductive/developmental screening study.