Olefines polymer, oxidized, hydrolyzed, distn. residues, from C20 alcohols manuf.

Endpoint summary

Description of key information

The key data is from a reliable (Klimisch 2) 26 week oral gavage study using docosan-1-ol in rats. In this study a NOAEL > 1000 mg/kg was reported. A read across from a reliable 13 week dietary study in rats using hexan-1-ol reported a NOAEL of 1127 mg/kg for males and 1243 mg/kg bw/day for females (Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study reasonably well documented, meets generally accepted scientific principles, acceptable for assessment of the limited parameters assessed. The study is read across from 1-hexanol (CAS 111-27-3).

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rats treated via the diet for 90 days with limited evaluation

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc.
- Age at study initiation: no data but "young"
- Weight at study initiation: males 103.6 g, females 90.5 g
- Fasting period before study: no data
- Housing: individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data but "controlled within narrow limits"
- Humidity (%): no data but "controlled within narrow limits"
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): basal laboratory diet (Purina Laboratory Chow)
- Storage temperature of food: no data

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

continuous in diet

Remarks:

Doses / Concentrations:
0.25%, 0.50%, 1.0-6.0%
Basis:
nominal in diet

No. of animals per sex per dose:

10 (treated), 20 (controls)

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: no satellite groups

Positive control:

none

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 5 days/week
- Cage side observations included: general physical appearance, gross signs of systemic toxicity and/or pharmacological effect, behaviour, mortality

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Time schedule for examinations: weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as mg/kg bw/day: Yes

FOOD EFFICIENCY: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: days 30 and 90
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 5/sex per group
- Parameters examined: microhaematocrit, haemoglobin, total and differential leukocyte count

CLINICAL CHEMISTRY: No

URINALYSIS: Yes
- Time schedule for collection of urine: days 30 and 90
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- How many animals: 5/sex per group (samples pooled)
- Parameters examined: albumin, acetone, bilirubin, colour, occult blood, sugar, pH, appearance, microscopic examination of sediment

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

ORGAN WEIGHTS: brain, thyroid, heart, liver, spleen, kidneys, adrenals, gonads (testes or ovaries)

HISTOPATHOLOGY: Yes
- brain, thyroid, parathyroid, heart, lung, liver, spleen, stomach, small intestine, large intestine, pancreas, kidney, urinary bladder, adrenal, gonad, lymph node, bone, bone marrow
- all listed tissues from 5/sex from high dose and controls examined

Other examinations:

none

Statistics:

Chi-squared test for comparing relative organ weights (but see 'Any other information on materials and methods')

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:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

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
- one male in low dose group died during week 9; cause of death was said to be unrelated to treatment
- occasional bloody encrustations of the eyes and nose
- otherwise no effects

BODY WEIGHT
- no effects

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
- food consumption 87.8% of controls in females in high dose group during week 13
- otherwise no effects

FOOD EFFICIENCY
- not examined

WATER CONSUMPTION
- not examined

OPHTHALMOSCOPIC EXAMINATION
- not examined

HAEMATOLOGY
- no effects other than "occasional aberrant value"

CLINICAL CHEMISTRY
- not examined

URINALYSIS
- high albumin, positive findings for occult blood; but no differences between treated and control groups

NEUROBEHAVIOUR
- not examined

ORGAN WEIGHTS
- some statistically significant effects (but see 'Remarks on results')

GROSS PATHOLOGY
- no effects

HISTOPATHOLOGY: NON-NEOPLASTIC
- no effects

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
- no effects

HISTORICAL CONTROL DATA (if applicable)
- no data

Dose descriptor:

NOAEL

Effect level:

1 127 mg/kg bw/day (actual dose received)

Sex:

male

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEL

Effect level:

1 243 mg/kg bw/day (actual dose received)

Sex:

female

Basis for effect level:

other: see 'Remark'

Critical effects observed:

not specified

ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX (means calculated from individual weekly dietary intake data)
0.25% M 182 mg/kg/day; F 216 mg/kg/day
0.5% M 374 mg/kg/day; F 427 mg/kg/day
1% M 1127 mg/kg/day; F 1243 mg/kg/day

Organ weights: The original report indicates that there were significant differences in some relative organ weights from treated groups compared 

to controls. 

Conclusions:

In a reliable study, the NOAEL for Alfol 6 in rats following 13 weeks dietary exposure was 1127 mg/kg bw/day for males and 1243 mg/kg bw/day for females (highest doses tested).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 243 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

This study examined male nad female albino rats for 13 weeks. Exposure to hexan-1-ol was through the diet. There were no clinical signs of toxicity or mortality and no changes in body weight or food consumption. Hematological, gross, and histopathological examinations showed no adverse signs. The NOAEL was 1127 mg/kg bw/day for males and 1243 mg/kg bw/day for females (highest doses tested).

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

Olefines polymer, oxidized, hydrolyzed, distillation residues, are by-products of the C20 alcohols manufacturing process. The substance, ‘Olefines polymer, oxidized, hydrolyzed, distillation. residues, are by-products from C20 alcohols manufacturing’, is a UVCB substance that comprises several linear long chain alcohols, predominantly docosan-1-ol (C22), tetracosan-1-ol (C24), hexacosan-1-ol (C26) and eicosan-1-ol (C20). Together, these constituents make up over 80% of the composition ofOlefines polymer, oxidized, hydrolyzed, distillation. residues, are by-products from C20 alcohols manufacturing. Other constituents include, to a much lesser extent, secondary long chain alcohols and complex mixtures of long chain carboxylate esters. On this basis, study data, where available, for each of the long chain alcohol constituents has been evaluated and considered together; this is consistent with the Category approach applied for Long Chain Alcohols (LCA) under REACH. 

 Available data for D-002, a defined mixture of higher aliphatic alcohols (triacontanol, octacosanol, dotriacontrianol, hexacosanol, tetracosanol) isolated from beeswax, has also been considered in this evaluation.

In a conservative approach the most sensitive study result from the constituents of the LCA category have been identified and used to address the endpoint in question.

Data from a reliable (Klimisch 2) 26 week oral gavage study using docosan-1-ol in rats reported a NOAEL > 1000 mg/kg. In addition a 26 week oral study in dogs reported a NOAEL >2000 mg/kg. In a reliable study, the NOAEL for hexan-1-ol in rats following 13 weeks dietary exposure was 1127 mg/kg bw/day for males and 1243 mg/kg bw/day for females (highest doses tested). A subchronic study on D-002 in mice lead to the conclusion that D-002 is non-toxic with a NOAEL of 625 mg/kg/day and a chronic study on beagles also reported no toxic effects in doses up to 250 mg/kg/day. Chronic and sub-chronic toxicity studies have shown that long chain alcohols (LCA) are of low toxicity. Furthermore, combined repeated-dose studies with developmental endpoints, as well as reproductive and developmental studies showed no effects at the highest dose tested. Consequently in line with the read-across justification included, Olefines polymer, oxidized, hydrolyzed, distillation residues, a by-product of C20 alcohol manufacturing, is considered to be of low toxicity with a NOAEL established at 1000mg/kg (for sub-chronic exposures).

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
This reliable Klimisch 2 study meets the generally accepted scientific principles and is acceptable for assessment.

Justification for classification or non-classification

These findings do not warrant the classification of Olefines polymer, oxidized, hydrolyzed, distillation residues, a by-product of C20 alcohols manufacturing, as repeated dose toxicant under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) and under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.