Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
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: Comparable to guideline study without detailed documentation (publication).
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: ICH Harmonised Tripartite Guideline S5(R2) Detection of toxicity to reproduction for medicinal products and toxicity to male fertility
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
Deviations:
yes
Remarks:
(no postnatal observations of pups)
GLP compliance:
not specified
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: (P) males 6-7 wks, females 10-11 weeks
- Weight at study initiation: (P) males 193-240 g; females 208-262 g
- Fasting period before study: no
- Housing: according to the investigators "during the acclimation and premating periods, 10 rats (5 males and 5 females) were housed per TR18 stainless-steel cage..."; during mating, 1 male and 1 female housed in RB3-modified high-grade polypropylene cage with stainless-steel mesh lids and floors; during gestation, 5 females per RB3-modified cage; after mating, 5 males per TR18 cage
- Use of restrainers for preventing ingestion (if dermal): not applicable
- Diet (e.g. ad libitum): expanded rodent diet (Special Diet Services Ltd.), ad libitum
- Water (e.g. ad libitum): public supply, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18
- Humidity (%): 55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
other: 1% w/w aqueous Tween 80
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
- test material weighed into glass container and heated to ~80 deg C until molten
- vehicle heated to 75 deg C
- test material and vehicle combined using coninuous magnetic stirring, 20% behenyl alcohol
- suspension cooled slowly to <60 deg C
- further cooled to 30 deg C
- slowly homogenized <=2 min
- cooled to room temperature
- 20% suspension prepared weekly
- 20% suspension provided top dose
- mid and low dose prepared on day of use by dilution with vehicle; 20% suspension magnetically stirred prior to removal of aliquots for dilution; dilutions hand swirled prior to magnetic stirring

VEHICLE
- Justification for use and choice of vehicle (if other than water): not stated
- Concentration in vehicle: 20, 2 and 0.2%
- Amount of vehicle (if gavage): 5 ml/kg bw
- Lot/batch no. (if required): no data
- Purity: 1% aqueous
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: not stated
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of gestation
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: no data
- Further matings after two unsuccessful attempts: no data
- After successful mating each pregnant female was caged (how): 5/cage; RB3-modified cages
- Any other deviations from standard protocol: OECD guideline 415 recommends that: pregnant females are house individually, the mating period should be 3 weeks
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Males: from 71 days prior to mating, during mating and until females sacrificed
Females: from 15 days prior to mating, during mating, and up to day 17 of gestation; killed on day 20 of gestation
Frequency of treatment:
daily
Details on study schedule:
1-generation study
Remarks:
Doses / Concentrations:
10, 100, 1000 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
22
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: previous repeated dose toxicity study NOAEL was 1000 mg/kg bw/day
- Rationale for animal assignment (if not random): no data
Positive control:
no
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: evidence of reaction to treatment, moribund condition, mortality

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: males and females twice weekly prior to mating; males twice weekly after mating; females on gestation days 0, 3, 7, 10, 14, 18 and 20

FOOD CONSUMPTION :
- Food consumption: Yes
- Time schedule: males weekly prior to mating, females daily prior to mating, females on gestation days 0-2, 3-6, 7-9, 10-13, 14-17, 18-19

WATER CONSUMPTION: Yes
- Time schedule: males weekly prior to mating, females daily prior to mating, females on gestation days 0-2, 3-6, 7-9, 10-13, 14-17, 18-19
Oestrous cyclicity (parental animals):
10 days prior to mating, daily vaginal smears to assess regularity and duration of oestrus cycles
Sperm parameters (parental animals):
Parameters examined in male parental generations: testis weight, epididymis weight, sperm count in epididymides, sperm motility
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no, F1 generation examined as foetuses on day 20 of gestation

PARAMETERS EXAMINED
The following parameters were examined in parental females and F1 offspring: numbers of implantation sites, early and late resorptions and viable foetuses; distribution of foetuses in each uterine horn; placental weight; macroscopic examination of placentae; number and sex of foetuses

EXAMINATION OF PUPS: yes, for external and internal abnormalities (visceral and skeletal)
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals following necropsy of the females
- Maternal animals: All surviving animals on day 20 of gestation

GROSS NECROPSY
- Gross necropsy of females consisted of reproductive endpoints only
- Gross necropsy of males consisited of macroscopic examination externally and internally; sperm assessment

HISTOPATHOLOGY / ORGAN WEIGHTS
No tissues were prepared for microscopic examination
Reproductive organs were weighed
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring were examined on day 20 of gestation
- These animals were subjected to examination as follows: each foetus weighed; detailed external examination; contents of cervical, thoracic and abdominal cavities removed from half the foetuses and examined and sex recorded; these foetuses stained for skeletal examination; remaining foetuses examined for visceral abnormalities

HISTOPATHOLOGY / ORGAN WEIGTHS
No tissues prepared for microscopic examination or weighed.
Statistics:
One-way analysis of variance, t-tests - body weight, body weight change, food and water consumption; Dunnetts' or Behren's-Fisher's tests - organ weights; nested analysis of variance, weighted t-tests - foetal and placental weights
Reproductive indices:
number of pregnant females, fertility
Offspring viability indices:
number of viable young (offspring evaluated as foetuses on day 20 of gestation)
Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Other effects:
not examined
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
- females, no mortality
- males, one death in top dose group in week 6, not considered to be treatment related in the absence of toxic signs in any other animals

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
- no effects

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
- no effects

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
- PREGNANCY RATE - no effects (22, 22, 22 and 21 in control, low, mid and high dose groups respectively)
- no effects

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
- no effects

ORGAN WEIGHTS (PARENTAL ANIMALS)
- males, reproductive organs, no effects

GROSS PATHOLOGY (PARENTAL ANIMALS)
- no effects

HISTOPATHOLOGY (PARENTAL ANIMALS)
- not examined

OTHER
- REPRODUCTIVE PARAMETERS
- Number of corpora lutea - no effects (17.8, 18.4, 18.7 and 18.9 for controls, low, mid and high dose respectively)
- Number of implantations - no effects (means 17.2, 17.0, 18.1 and 18.0 for controls, low, mid and high dose respectively)
- Number of viable young - no effects (means 16.4, 15.9, 17.0 and 16.9 for controls, low, mid and high dose  respectively)
- Sex ratio - no effects
- Number of resorptions (early or late) - no effects
- Pre-implantation loss - no effects (3.3, 8.3, 3.2,  5.8% for controls, low, mid and high dose respectively)
- Post-implantation loss - no effects (4.7, 6.4, 6.3 and 5.8% for controls, low, mid and high dose respectively)
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: overall effects
Clinical signs:
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not examined
VIABILITY (OFFSPRING)
- no effects

CLINICAL SIGNS (OFFSPRING)
- not applicable, foetuses examined at day 20 of gestation

BODY WEIGHT (OFFSPRING)
- no effects

SEXUAL MATURATION (OFFSPRING)
- not applicable, foetuses examined at day 20 of gestation

ORGAN WEIGHTS (OFFSPRING)
- not applicable, foetuses examined at day 20 of gestation

GROSS PATHOLOGY (OFFSPRING)
- not applicable, foetuses examined at day 20 of gestation

HISTOPATHOLOGY (OFFSPRING)
- not applicable, foetuses examined at day 20 of gestation

OTHER FINDINGS (OFFSPRING)
- MACROSCOPIC EXAMINATION (OFFSPRING)
- no variations were observed that were not comparable to historical control values
- SKELETAL EXAMINATION (OFFSPRING)
- no variations were observed that were not comparable to historical control values
- VISCERAL EXAMINATION (OFFSPRING)
- no variations were observed that were not comparable to historical control values
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: overall effects
Reproductive effects observed:
not specified
Conclusions:
In a reliable study, conducted to a protocol similar to OECD guideline 415, an NOAEL of 1000 mg/kg bw/day was determined in the rat for reproductive effects. The study was performed in compliance with GLP.
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Male and female Sprague Dawley rats were chosen for a one-generation reproductive toxicity study. Reproduction function in the male and female was examined as well as reproductive performance, both which had no changes due to treatment. Parental animals had no changes in body weight, histopathological or gross pathological parameters. Offpsring also had no effects seen for viability or gross pathology.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
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. 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.

 

The conclusion that the members of the aliphatic alcohol category (C6 to C22) are  not expected to impair fertility is based on a weight of evidence approach using data from reproductive  screening studies [C12 (dodecanol), C18 (octadecanol)],a fertilitystudy [C22 (docosanol)], together with a lack of effect on the reproductive organs in repeat dose studies over the range of linear and  essentially linear alcohols. In addition there have been no other treatment related effects reported in any of the other studies both using icosan-1-ol and other alcohols from the category. 

On the basis of this reproductive toxicity information included as part of this submission and in line with the read-across justification it is concluded that Olefines polymer, oxidized, hydrolyzed, distillation residues, a by-product of C20 alcohols manufacturing, is not likely to impair fertility.


Short description of key information:
A reliable one-generation reproduction study using docosan-1-ol in rats reported a NOAEL of 1000 mg/kg.

A read across feeding study reported a lack of effects on the reproductive organs of rats receiving hexan-1-ol (Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study.

A study on male and female NMRI mice over a 6 or 8 week period reported doses of D-002 up to 625 mg/kg-day that showed no sign of reproductive toxicity.

Justification for selection of Effect on fertility via oral route:
In a reliable (Klimisch 2) generational study, conducted to a protocol similar to OECD guideline 415 and performed in compliance with GLP. The appropriate species, doses groups, animals per dose and time period was selected.

Effects on developmental toxicity

Description of key information
A reliable developmental toxicity study using docosan-1-ol in rabbits reported a NOAEL for developmental and maternal effects of > 2000 mg/kg. 
Link to relevant study records
Reference
Endpoint:
developmental toxicity
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: Comparable to guideline study without detailed documentation (publication).
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: ICH Harmonized Tripartite Guideline S5 (R2) for Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
(non standard examination of soft tissue and head of foetuses)
GLP compliance:
not specified
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Froxfield SPF Rabbits Ltd., UK
- Age at study initiation: 18-26 weeks on arrival
- Weight at study initiation: 3.29-4.98 kg at start of study
- Fasting period before study: no data
- Housing: individually in suspended stainless-steel cages (TR6)
- Diet (e.g. ad libitum): standard rabbit diet (Special Diets Services Ltd., UK), ad libitum
- Water (e.g. ad libitum): public supply, ad libitum
- Acclimation period: >=1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18
- Humidity (%): 55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
other: 1% Tween 80
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
- test material weighed into glass container and heated to ~80 deg C until molten
- vehicle heated to 75 deg C
- test material and vehicle combined using coninuous magnetic stirring, 20% behenyl alcohol
- suspension cooled slowly to <60 deg C
- further cooled to 30 deg C
- slowly homogenized <=2 min
- cooled to room temperature
- 20% suspension prepared weekly
- 20% suspension provided top dose
- mid and low dose prepared on day of use by dilution with vehicle; 20% suspension magnetically stirred prior to removal of aliquots for dilution; dilutions hand swirled prior to magnetic stirring

VEHICLE
- Justification for use and choice of vehicle (if other than water): not stated
- Concentration in vehicle: 20, 2 and 0.2%
- Amount of vehicle (if gavage): 10 ml/kg bw for vehicle control and top dose groups; 0.625 and 2.5 ml/kg bw for low and mid dose groups respectively
- Lot/batch no. (if required): no data
- Purity: 1%
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Impregnation procedure: cohoused with males of establised fertility
- If cohoused:
- M/F ratio per cage: no data
- Length of cohabitation: no data
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: no data
- Further matings after two unsuccessful attempts: no data
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: not specified, but referred to as day 0 of pregnancy
- Any other deviations from standard protocol: no data
Duration of treatment / exposure:
days 6-19 of gestation
Frequency of treatment:
daily
Duration of test:
females killed on day 29 of gestation
Remarks:
Doses / Concentrations:
125, 500, 2000 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
22
Control animals:
yes, concurrent vehicle
Details on study design:
Sex: female
Duration of test: 28 days
- Dose selection rationale: based on previous range-finding study
- Rationale for animal assignment (if not random): randomly allocated to the four treatment groups in order of mating "to evenly distribute the mated females among the groups"
- Other:
- approximately 2 weeks prior to arrival of females at testing facility, oestrus synchronised by supplier by intravenous injection of 25 IU luteinizing hormone
- following insemination, females injected intravenously with 25 IU luteinizing hormone to ensure successful ovulation
- examined on day 6 of gestation, prior to dosing, to determine suitability for use in study
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: evidence of reaction to treatment or moribund condition

DETAILED CLINICAL OBSERVATIONS: no data

BODY WEIGHT: Yes
- Time schedule for examinations: daily

FOOD CONSUMPTION: Yes
- Time schedule for examinations: days 1-5, days 6-12, days 13-19, days 20-23, days 24-28

WATER CONSUMPTION: Yes
- Time schedule for examinations: daily

POST-MORTEM EXAMINATIONS: yes, macroscopic examination
- Sacrifice on gestation day 29
- Organs examined in addition to uterine contents and ovaries: no data
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other:
- Number of viable young: males, females and total
- Distribution of foetusus in each uterine horn
- Uterus of any female presumed non-pregnant stained and examined for implantation sites
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter - cervical, thoracic and abdominal cavities dissected and contents examined microscopically
- Skeletal examinations: Yes: all per litter
- Head examinations: Yes: one third per litter
- Other: all per litter
- foetal body weight
- position of foetus in uterus
- placental weight
Statistics:
One-way analysis of variance, t-tests - body weight, body weight change, food and water consumption; Dunnett's or Behren's-Fisher's tests - organ weights; nested analysis of variance, weighted t-tests - foetal and placental weights
Indices:
no data
Historical control data:
no data
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
no effects other than pale faeces in animals of the top dose group
Dose descriptor:
NOAEL
Effect level:
2 000 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
no effects
Dose descriptor:
NOAEL
Effect level:
2 000 mg/kg bw/day (actual dose received)
Basis for effect level:
other: teratogenicity
Abnormalities:
not specified
Developmental effects observed:
not specified

Table 1: Reproductive and developmental parameters

Observation

Dose (mg/kg bw/day)

0

125

500

2000

Animals Assigned (Mated)

22

22

22

22

Animals Pregnant

Pregnancy Rate (%)a

20

91%

19

86%

19

86%

20

91%

Nonpregnant

2

3

3

2

Total litter loss

(%)a

1

10.0%

1

5.3%

1

5.3%

0

0.0%

Corpora Lutea/Dam (mean±SD)

12.8±3.1

12.9±2.2

12.6±3.0

12.2±3.9

Implantations/Dam (mean±SD)

11.4±3.9

11.1±2.6

11.0±3.3

10.6±4.3

Live Fetuses/Dam (mean±SD)

Male (mean±SD)

Female (mean±SD)

10.1±3.7

4.6±2.6

5.5±2.4

9.8±2.1

4.8±1.5

4.9±1.7

9.3b±2.6

3.8±1.5

5.5±2.1

9.0±3.8

4.7±2.2

4.3±2.5

Resorptions/Dam (mean±SD)

Early (mean±SD)
Late (mean±SD)

1.4±1.2

0.4±0.6

1.0±1.0

1.3±1.2

0.3±0.5

1.1±1.0

1.7±1.3

0.4±0.6

1.2±1.1

1.6±1.2

0.7±0.8

0.9±0.9

Preimplantation Loss (%)

10.4

14.2

13.9

13.5

Postimplantation Loss (%)

12.1

12.0

15.2

14.7

aCalculated for this table

bIncludes one foetus not sexed at necropsy

Conclusions:
In a reliable study, conducted according to a protocol similar to OECD guideline 414, the NOAEL for maternal toxicity, teratogenicity and foetotoxicity in rabbits, was 2000 mg/kg/day (highest dose tested). The study was performed in compliance with GLP.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subchronic
Species:
rabbit
Quality of whole database:
Female New Zealand white rabbits were treated on days 6-19 of gestation to examine maternal and embryotoxic effects. Three dose groups were chosen and 22 rabbits were placed in each group. Both maternal and fetal examinations were made. There were no maternal effects except for pale faces in the highest dose group and there were no embryotoxic or teratogenic effects.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
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. 

A reliable (Klimish 2) study examining the developmental and teratogenicity of D-002, a defined mixture of higher aliphatic alcohols (triacontanol, octacosanol, dotriacontrianol, hexacosanol, tetracosanol) isolated from beeswax, has also been considered. Both Sprague Dawley rats and New Zealand White rabbits showed no maternal or fetal adverse effects due to gestational exposure to doses of D-002 up to 1000 mg/kg bw/day.

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.

 

Based on the weight of evidence from other alcohols across the category it is concluded that icosan-1-ol, docosan-1-ol, and D-002 are unlikely to be a developmental toxicant in the absence of maternal toxicity. Consequently on the basis of this information Olefines polymer, oxidized, hydrolyzed, distillation residues, a by-product of C20 alcohols manufacturing, is also unlikely to be developmental toxicant in the absence of maternal toxicity.


Justification for selection of Effect on developmental toxicity: via oral route:
Comparable to guideline study without detailed documentation and in GLP compliance.

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 reproductive/developmental 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.

Additional information