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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Description of key information

No significant concern can be reliably derived for the registration substance with respect to the endpoint reproduction toxicity based on the read-across to alkyl alcohol ethoxylates.

Link to relevant study records
Reference
Endpoint:
two-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
GLP study; considered as reliable by experts groups of HERA and CIR
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Deviations:
yes
Remarks:
3 applications per week / no treatment during mating
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
Test material: C9-11 pareth 6 (mixture of C9-11 alkyl alcohol with 6 ethoxylation unit)
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
dermal
Vehicle:
water
Details on exposure:
Dose volume: 1 mL/kg bw
Details on mating procedure:
1:1 ration of cohabitation; avoid of sibling or half-sibling mating
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
F0 generation: 119 days prior to mating
F1 generation: 133 days prior to mating
Frequency of treatment:
3/week (except during mating)
Details on study schedule:
P: 119 days of dosing
F1: 133 days of dosing
Dose / conc.:
0 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 0% test material (w/v) in water
Dose / conc.:
1 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 10% test material (w/v) in water
Dose / conc.:
100 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 10% test material (w/v) in water
Dose / conc.:
250 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 25% test material (w/v) in water
No. of animals per sex per dose:
F0: 30 males and 30 females
F1: 20 males and 20 females
Control animals:
yes, concurrent vehicle
Details on study design:
The F0 groups, consisting of 30 males and 30 females, were exposed dermally to 1 mL/kg of 0%, 1%, 10% or 25% w/v aqueous test material for 119 days prior to mating. The test site was shaved, but the application sites were not covered. The test material was not applied during mating to avoid ingestion. Among the F1 generation, groups of 20 males and 20 females per test group were mated. The male rats of both generations were killed following mating.
On day 4 of lactation, any litter with more than 10 pups was culled to 10.
Parental animals: Observations and examinations:
Weekly body weight investigation of males and females up to the time of mating; weekly body weight investigation of females during gestation and lactation;
Sperm parameters (parental animals):
Enumeration of sperm heads and LDH-X activity of left testes of each F0 and F1 male.
Litter observations:
- Litter weight investigation on days 1, 4,7,21 and 28 of lactation; Individual body weight of pups on day 28 of lactation
- At parturition litter size, sex of pups, number of live and sillborn pups.
- Daily observation of pups mortality and physical abnormalities.
Postmortem examinations (parental animals):
Gross necropsies on all F0 and F1 parents; histopathological examinations included all reproductive organs, all lesions in F0 parents; Organ weights of the reproductive organs, liver, spleen, heart, kidney and lung in F1 parents.
Postmortem examinations (offspring):
Gross necropsies, histopathological examinations and organ weights on selected F1 and F2 pups (5/sex/dose)
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
effects observed, treatment-related
Description (incidence and severity):
No irritation was observed for any of the animals, but dry flaking skin was observed in the 10% and 25% dose groups.
Mortality:
mortality observed, non-treatment-related
Description (incidence):
Five death was observed in the F1 adult in the ctronol and treatment group, not treatment related
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Minimal decrease at 25%.
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Description (incidence and severity):
No effects regarding organ weights, mating indices, fertility indices, or mean gestational length.
Key result
Dose descriptor:
NOAEL
Remarks:
reproductive performance
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect up to the highest dose level
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect up to the highest dose level
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
effects observed, treatment-related
Description (incidence and severity):
No irritation was observed for any of the animals, but dry flaking skin was observed in the 10% and 25% dose groups.
Mortality:
mortality observed, non-treatment-related
Description (incidence):
Five death in the P1/F1 animals in control and treatment groups.
Body weight and weight changes:
effects observed, non-treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
Weight change in liver, lung, kidney and heart in P1/F1 animals
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Description (incidence and severity):
No effects regarding organ weights, mating indices, fertility indices, or mean gestational length.
Key result
Dose descriptor:
NOAEL
Remarks:
reproductive performance
Effect level:
>= 250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect up to the highest dose level
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
>= 250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect up to the highest dose level
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
effects observed, treatment-related
Description (incidence and severity):
No irritation was observed for any of the animals, but dry flaking skin was observed in the 10% and 25% dose groups.
Mortality / viability:
mortality observed, non-treatment-related
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Five death in the P1/F1 animals in control and treatment groups.
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
Weight change in liver, lung, kidney and heart in P1/F1 animals.
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Generation:
F1
Effect level:
>= 250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect up to the highest dose level
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Generation:
F2
Effect level:
>= 250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect was observed up to the highest dose level
Key result
Reproductive effects observed:
no
Executive summary:

In a two-generation reproduction study, Fischer 344 rats were dermally exposed to 1 mL/kg bw C9-11AE6 (CAS 68439-46-3) at concentrations of 0, 1, 10 or 25% w/v three times a week except during the mating periods. This treatment equals exposure levels of about 0, 10, 100 and 250 mg/kg bw/day. No mortalities were observed in the parental generation, and the deaths in the P1/F1 adult males and females in the control and treatment groups were not considered to be treatment related. In the highest dose group, body weights of both males and females in both treated generations were sporadically decreased compared to controls. There was no effect on maternal body weight during gestational and lactational periods in both generations. At necropsy organ weight differences in liver, lung, kidney and heart were observed in the F1 generation. However no pathological findings were associated with these affected organs. There were no compound-related effects on mating and fertility indices and mean gestational length in both generations. No effects on testicular weights, sperm counts and LDH-X activities in P0 and P1/F1 male adults were observed. Macroscopic and microscopic examination of the reproductive organs did not reveal significant differences in the treated groups compared to the controls. Based on these observations the NOAEL for reproductive and developmental toxicity can be established at 250 mg/kg bw/day, the highest dermally tested dose.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
robust and reliable
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
robust and reliable
Additional information

The reproduction toxicity of the registration substance is to be derived based on the read-across to alkyl alcohol ethoxylates. The justification of the read-across is provided as attached document in the dossier.

Three two-generations studies in rats on read-across supporting substances are availale, two feeding studies and one dermal studies. Consistent effects in all three studies were found, so that the route of application does not seem to influence the systemic toxicity or reproductive performance: the major effect found at dose of 250 mg/kg bw was reduced body weight gain and increased liver weight in absence of any effect on the reproduction performance on the parental animals.

In a GLP-compliant two-generation reproduction study, Fischer 344 rats were dermally exposed to 1 mL/kg bw C9-11AE6 (CAS 68439-46-3) at concentrations of 0, 1, 10 or 25% w/v three times a week except during the mating periods. This treatment equals exposure levels of about 0, 10, 100 and 250 mg/kg bw/day. No mortalities were observed in the parental generation, and the deaths in the P1/F1 adult males and females in the control and treatment groups were not considered to be treatment related. In the highest dose group, body weights of both males and females in both treated generations were sporadically decreased compared to controls. There was no effect on maternal body weight during gestational and lactational periods in both generations. At necropsy organ weight differences in liver, lung, kidney and heart were observed in the F1 generation. However no pathological findings were associated with these affected organs. There were no compound-related effects on mating and fertility indices and mean gestational length in both generations. No effects on testicular weights, sperm counts and LDH-X activities in P0 and P1/F1 male adults were observed. Macroscopic and microscopic examination of the reproductive organs did not reveal significant differences in the treated groups compared to the controls. Based on these observations the NOAEL for reproductive and developmental toxicity can be established at 250 mg/kg bw/day, the highest dermally tested dose.

The reproductive toxicity of C14-15AE7 (CAS 68951 -67 -7) was evaluated in a two-generation study conducted in Charles River CD rats. One control group and six treatment groups of 50 animals (25 males and 25 females) were used in this study. Compound administration was carried out at dietary levels of 0.05%, 0.1% and 0.5% (i.e., approximately 25, 50 and 250mg/kg bw/d). Three of the treatment groups received the dietary levels of the compound throughout the study. Of the remaining three treatment groups, only the females received the compound during the 6th and 15th day of gestation. The males were not treated in these latter groups. No compound-related differences were observed between control and treatment groups in terms of fertility, gestation or viability indices. Therefore, a NOAEL for reproduction at a dietary intake level greater than 0.5% was determined which corresponds to a dose of 250 mg/kg bw/d.

The reproductive toxicity of C12AE6 was evaluated in a two-generation feeding study. Rats were exposed to the compound at dose levels of 25, 50 or 250 mg/kg bw/d. No treatment-related effects in the parents or pups on general behaviour, appearance or survival were observed. Fertility of the treated groups was comparable with the controls. The only observation was related to a reduced weight gain of parental rats and pups relative to the control at the highest dose level (i.e., 250 mg/kg bw/d). The NOAEL for reproduction was therefore set at the highest dose level which was 0.5% dietary level greater than 250 mg/kg bw/d.

Further evidence for the lack of reproductive toxicity of alcohol ethoxylates has been provided by a range of subchronic oral feeding studies which investigated also any potential effects on the organs of the reproductive system (see Chapter 7.5). None of these studies revealed any adverse effects of exposure to AE on the reproductive system.

 


Effects on developmental toxicity

Description of key information

No significant concern can be reliably derived for the registration substance with respect to the endpoint developmental toxicity based on the read-across to alkyl alcohol ethoxylates.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
GLP study; considered as reliable by experts groups of HERA and CIR
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD 416
Deviations:
yes
Remarks:
Only 3 applications per week/ no treatment during mating
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Fischer 344
Route of administration:
dermal
Vehicle:
water
Details on exposure:
Dose volume: 1 mL/kg bw
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
F0 generation: 119 days prior to mating
F1 generation: 133 days prior to mating
Frequency of treatment:
3/week (except during mating)
Duration of test:
P: 119 days of dosing
F1: 133 days of dosing
Dose / conc.:
0 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 0% test material (w/v) in water
Dose / conc.:
10 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 1% test material (w/v) in water
Dose / conc.:
100 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 10% test material (w/v) in water
Dose / conc.:
250 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 25% test material (w/v) in water
No. of animals per sex per dose:
30 (P)
20/40 (male/female; F1)
Control animals:
yes, concurrent vehicle
Details on study design:
The P0 groups, consisting of 30 males and 30 females, were exposed dermally to 1 mL/kg of 0%, 1%, 10% or 25% w/v aqueous test material for 119 days prior to mating. The test site was shaved, but the application sites were not covered. The test material was not applied during mating to avoid ingestion. Among the F1 generation, groups of 20 males and 20 females per test group were mated. The male rats of both generations were killed following mating.
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
effects observed, treatment-related
Description (incidence and severity):
No irritation was observed for any of the animals, but dry flaking skin was observed in the 10% and 25% dose groups.
Mortality:
mortality observed, non-treatment-related
Description (incidence):
Five death was observed in the F1 adult in the ctronol and treatment group, not treatment related
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Minimal decrease at 25%.
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
Weight change in liver, lung, kidney and heart in P1/F1 animals
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed
Description (incidence and severity):
No effects regardin mating indices, fertility indices, or mean gestational length.
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: No significant effect up to the highest dose level
Remarks on result:
other:
Remarks:
The NOAEL obtained in a two generation reproduction toxicity study
Key result
Dose descriptor:
NOAEL
Remarks:
reproductive performance
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: No significant effect up to the highest dose level
Remarks on result:
other:
Remarks:
The NOAEL obtained in a two generation reproduction toxicity study
Key result
Dose descriptor:
NOAEL
Remarks:
developmental
Effect level:
>= 250 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: Up to 250 mg/kg bw no significant effect onthe growth and developmental of the offspring was found in the two generation reproduction toxicity study
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Executive summary:

In a GLP-compliant 2-generation reproduction study, groups of thirty weanling rats of each sex were treated dermally with 1 mL/kg bw of C9-11AE6 at concentration of 0, 1, 10 or 25% w/v (0, 10, 100 or 250 mg/kg bw/d) three times a week except during the mating periods. No compound related effects on litter size, number of live pubs and sex ratio of pups in the F1 and F2 generations were observed. Low incidences of foetal malformations were observed, but these were not dose related and considered to be of spontaneous nature. At necropsy, no effects were observed in the F1 pups. In the F2 pups, a significantly higher carcass weight in the females of the 250 mg/kg bw/d dose group was noted and some minor organ weight differences. Due to the lack of a doseresponse and no associated morphological findings, these effects were considered to be of no toxicological significance. It was concluded that dermal application of C9-11AE6 to rats did not induce any adverse effects on the growth and development of the offspring during two generations. The NOAEL of C9-11AE6 with respect to developmental and teratogenic toxicity can be assumed to be higher than the highest dose level dermally applied in this study (i.e., 250 mg/kg bw/d)

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
chronic
Species:
other: rat and rabbit
Quality of whole database:
robust and reliable
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
robust and reliable
Additional information

The developmental toxicity of the registration substance is to be derived based on the read-across to alkyl alcohol ethoxylates. The justification of the read-across is provided as attached document in the dossier.

Total four studies are available on read-across substances, which allows to assess the developmental toxicity of the registration substances.

In three two-generation studies (two by feeding and one by dermal), the only effect found in the offsprings (F1 and F2 animals) were limited to increased liver weight at doses that were associated with parental toxicity. Also in rabbit study no indication of developmental toxicity was found up to doses that were apparently associated with maternal toxicity.

In a GLP-compliant 2-generation reproduction study, groups of thirty weanling rats of each sex were treated dermally with 1 mL/kg bw of C9-11AE6 at concentration of 0, 1, 10 or 25% w/v (0, 10, 100 or 250 mg/kg bw/d) three times a week except during the mating periods. No compound related effects on litter size, number of live pubs and sex ratio of pups in the F1 and F2 generations were observed. Low incidences of foetal malformations were observed, but these were not dose related and considered to be of spontaneous nature. At necropsy, no effects were observed in the F1 pups. In the F2 pups, a significantly higher carcass weight in the females of the 250 mg/kg bw/d dose group was noted and some minor organ weight differences. Due to the lack of a doseresponse and no associated morphological findings, these effects were considered to be of no toxicological significance. It was concluded that dermal application of C9-11AE6 to rats did not induce any adverse effects on the growth and development of the offspring during two generations. The NOAEL of C9-11AE6 with respect to developmental and teratogenic toxicity can be assumed to be higher than the highest dose level dermally applied in this study (i.e., 250 mg/kg bw/d).

In a study with C12AE6 (CAS 9002 -92 -0), twenty-five female rabbits were orally administered doses of 0, 50, 100 or 200 mg/kg bw/d from day 2 to day 16 of gestation. Caesareans were performed on the 28th day of pregnancy. A definite increase in maternal toxicity, evidenced by ataxia and a slight decrease in body weight was observed at 100 and 200 mg/kg bw/d. No effects were observed for parameters such as corpora lutea, implantations, number of live foetuses and spontaneous abortions. Nine control rabbits and 31 treated rabbits died during the study. Surviving rabbits at the 200 mg/kg bw/d dose level generally showed slight losses of body weight. In seven treated and two control rabbits early deliveries were recorded. The NOAEL for this study based on the maternal toxicity was therefore assumed to be greater than 50 mg/kg bw/d level.

The reproduction and developmental toxicity of C14 -15AE7 (CAS 68951 -67 -7) was investigated in a two-generation study conducted in Charles River CD rats. One control group and six treatment groups of 50 animals (25 males and 25 females) were used in this study. Compound administration was carried out at dietary levels of 0.05%, 0.1% and 0.5% (i.e., approximately 25, 50 and 250mg/kg bw/d). Three of the treatment groups received the dietary levels of the compound throughout the study. Of the remaining three treatment groups, only the females received the compound during the 6th and 15th day of gestation. The males were not treated in these latter groups. In addition, on day 13 of gestation, laparotomies were performed on a representative number of female rats from the FC generation (i.e., offspring from the 3rd mating of the F0 and F1 parental generation). The uterus of the female rats was examined for uterine abnormalities, normal implantation and resorption sites. The remaining females were sacrificed on day 21 of gestation and corpora lutea were counted and the presence and distribution of live and dead foetuses was recorded. Foetuses were removed and examined for external abnormalities, sexed and weighed. A variety of measured maternal and foetal indices differed significantly from the control group, however these differences were not dose-related and so not attributed to the test compound. Parental female rate and pups of the high dose group did not gain as much body weight as the control rats. Examination of organ weight values revealed compound-related effects were limited to increased group mean liver weights of male and female P1 generation from the 0.5% continuous feeding group at the 91-day sacrifice and increase in group mean relative liver weights of males of the 0.5% continuous feeding group of the P2 generation at the 60-day section sacrifices. The NOAEL for maternal and developmental toxicity was established at the 50 mg/kg bw/d dose level.

The reproduction and developmental toxicity of C12AE6 (CAS 9002 -92 -0) was investigated in a two-generation study conducted in Charles River CD rats. One control group and six treatment groups of 50 animals (25 males and 25 females) were used in this study. Compound administration was carried out at dietary levels of 0.05%, 0.1% and 0.5% (i.e., approximately 25, 50 and 250mg/kg bw/d). Three of the treatment groups received the dietary levels of the compound throughout the study. Of the remaining three treatment groups, only the females received the compound during the 6th and 15th day of gestation. The males were not treated in these latter groups. General behaviour, appearance and survival were not affected by treatment. At the 0.5% dose level, adults and pups gained less weight than the control rats. In the 0.5% dose group, there was a statistical increase in embryo lethality and soft tissue anomalies and at the 0.1% there was a statistical decrease in mean foetal liver weight. Neither of these effects was considered to be treatment-related by the authors as they showed no dose response characteristics. Although not specifically reported, it appeared that NOAEL for maternal toxicity was 50 mg/kg bw/d. The NOAEL for developmental and teratogenic toxicity was set at the 0.1% dose level, equalling an exposure of about 50 mg/kg bw/d.

Justification for classification or non-classification

No significant concern could be reliably derived. No classificaiton is justified.

Additional information