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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS No. 68583-51-7). In accordance to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Justification for type of information:
The Glycol ester category covers esters of an aliphatic diol (ethylene glycol (EG), propylene glycol (PG) or 1,3-butyleneglycol (1,3-BG)) and one or two carboxylic fatty acid chains. The fatty acid chains comprise carbon chain lengths ranging from C6 to C18, mainly saturated but also mono unsaturated C16 and C18, branched C18 and epoxidized C18.
 
The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, 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 grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Decanoic acids, mixed diesters with octanoic acid and propylene glycol
- Physical state: colourless liquid
- Analytical purity: 100% active substance
- Lot/batch No.: 3472

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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

Administration / exposure

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

Examinations

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

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):
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.

Effect levels

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

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

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.

Applicant's summary and conclusion