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Administrative data

Description of key information

The available repeated dose toxicity studies of the read across substances administered via diet provide a coherent picture on the subchronic oral toxicity of alcohols, alkylsulfates and alkyl ethersulfates and the lowest NOAEL (250 mg/kg bw/d Walker, 1967) was chosen for risk assessment.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
analogue approach for alkylethersulfates contained in registered substance - see attached read across justification.
Meets generally accepted scientific standards, well documented and acceptable for assessment.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
not specified
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
Sodium lauryl ethoxysulphate (3 EO)
Test item: Sodium lauryl (3EO) ethoxysulphate (C2; 24% w/w)
Species:
rat
Strain:
other: Carworth Farm 'E'
Sex:
male/female
Details on test animals or test system and environmental conditions:
Groups of 12 male and 12 female individually caged rats (aged 5 wk) were fed dietary levels of 40, 200, 1000 or 5000 ppm active material.
Control groups (18 males and 18 females) received Diet 86 powder (Withers Ltd., Godalruing, Surrey).
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Dose / conc.:
40 ppm
Dose / conc.:
200 ppm
Dose / conc.:
1 000 ppm
Dose / conc.:
5 000 ppm
No. of animals per sex per dose:
12 male and 12 female per dose
Control animals:
yes
Positive control:
no positive control
Observations and examinations performed and frequency:
Daily observations were made on health. Body weight and food intake were recorded weekly for all animals. Urine samples were obtained from the 5000 ppm and control groups during week 12 on test.
Sacrifice and pathology:
At autopsy, gross pathological examination was carried out and the major visceral organs were weighed (brain, heart, liver, spleen, kidneys, testes ). Sections of a wide range of organs from rats of the 5000 ppm and control groups were processed for histological examination.
Statistics:
Statistical analyses of terminal body weights, food intakes and organ weights were made using the initial body weight as a covariate in covariance analysis.
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):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Statistically increased kidney (p<=0.01), liver (p<=0.01) and heart (p<=0.05) weights in 5000 ppm dose group (females).
Statistically increased kidney (p<=0.05) weights in 5000 ppm dose group (females).
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
act. ingr. (total fraction)
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
gross pathology
haematology
mortality
organ weights and organ / body weight ratios
urinalysis
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Based on:
test mat. (total fraction)
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
gross pathology
haematology
mortality
organ weights and organ / body weight ratios
urinalysis
Critical effects observed:
not specified
Lowest effective dose / conc.:
5 000 ppm
System:
hepatobiliary
Organ:
liver
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
not specified
Critical effects observed:
not specified
Lowest effective dose / conc.:
5 000 ppm
System:
cardiovascular
Organ:
heart
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
not specified
Critical effects observed:
not specified
Lowest effective dose / conc.:
5 000 ppm
System:
urinary
Organ:
kidney
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
not specified
Executive summary:

Sodium lauryl ethoxysulphate (3 EO) was tested in a 90-day feeding study on rats.

Twelve male and 12 female rats/group were fed dietary levels of 40, 200, 1000 or 5000 ppm (corresponding to 2, 10, 50 or 250 mg/kg bw/day according to Guidelines for the preparation of toxicological working papers for the Joint FAO/WHO Expert Committee on Food Additives).

The control group (18 males, 18 females) received the diet alone. Daily observations were made on health. Body weight and food intake were recorded weekly. Urine samples were obtained from the 5000 ppm and control groups during week 12. The urine was examined for color, pH, protein, reducing substances, bile salts and microscopic constituents. Terminal blood samples were taken by cardiac puncture and erythrocyte and leucocyte counts and determinations of hematocrit and hemoglobin were made. Total plasma protein and urea were determined. Gross pathological and histological examination of a wide range of organs were made. The only effects observed occurred at 5000 ppm and comprised increases in heart, liver and kidney weights in female animals.

Endpoint:
chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
analogue approach for alkylethersulfates contained in registered substance - see attached read across justification.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 452 (Chronic Toxicity Studies)
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
other: Drinking water study & Feeding study
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Observations and examinations performed and frequency:
survival, growth, food consumption, body weights, clinical laboratory findings, hamatology and urinalyses.
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):
effects observed, treatment-related
Description (incidence and severity):
A slight, but consistently higher water consumption by all rats receiving the test compound in their drinking water and a significant
difference in the empty cecum to body weight ratio of females was oberved.
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
> 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Feeding study
Dose descriptor:
NOAEL
Effect level:
> 75 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Drinking water study
Critical effects observed:
no
Executive summary:

Poly(oxy-1,2-ethanediyl),a-sulfo-w-(dodecyloxy)-, sodium salt was tested in a chronic toxicity feeding and drinking water study comparable to a OECD 452 guideline study on rats. A NOAEL of 250 mg/kg bw/day (nominal, feeding) was reported.

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
analogue approach for fatty alcohols contained in registered substance - see attached read across justification.
Meets generally accepted scientific standards, well documented and acceptable for assessment.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
26 weeks treatment
GLP compliance:
yes
Limit test:
no
Species:
dog
Strain:
Beagle
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: 1% aqueous Tween 80
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
26 weeks
Frequency of treatment:
daily, 7 days/week
Dose / conc.:
20 mg/kg bw/day (nominal)
Remarks:
Doses / Concentrations:
20, 200, 2000 mg/kg bw-day
Basis:

Dose / conc.:
200 mg/kg bw/day (nominal)
Dose / conc.:
2 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
32
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: no
Positive control:
no
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
These were confined to observation of pale faeces in all dogs treated with 2000 mg/kg/day behenyl alcohol and 1 male and 3 females at 200 mg/kg/day. The incidence of this effect was variable and more pronounced in females. This was attributed to the presence in the gastrointestinal tract of unabsorbed test material. One control dog also had pale faeces on a single occasion.
Mortality:
mortality observed, treatment-related
Description (incidence):
These were confined to observation of pale faeces in all dogs treated with 2000 mg/kg/day behenyl alcohol and 1 male and 3 females at 200 mg/kg/day. The incidence of this effect was variable and more pronounced in females. This was attributed to the presence in the gastrointestinal tract of unabsorbed test material. One control dog also had pale faeces on a single occasion.
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Description (incidence and severity):
No treatment related changes
Haematological findings:
no effects observed
Clinical biochemistry findings:
not specified
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed
Details on results:
NOAEL: 2000 mg/kg/day

ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX
0. 20, 200 and 2000 mg/kg/day

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- Mortality and time to death: No deaths among treated or control animals.
- Clinical signs: These were confined to observation of pale faeces in all dogs treated with 2000 mg/kg/day behenyl alcohol and 1 male and 3 females at 200 mg/kg/day. The incidence of this effect was variable and more pronounced in females. This was attributed to the presence in the gastrointestinal tract of unabsorbed test material. One control dog also had pale faeces on a single occasion.
- Body weight gain: No effects.
- Food/water consumption: No effects.
- Ophthalmoscopic examination: No treatment related changes.
- Clinical chemistry: No effects.
- Haematology: No effects.
- Urinalysis: No effects.
- Organ weights: No effects.
- Gross pathology: No adverse effects.
- Histopathology: No adverse effects.
- Other: Concentrations of behenyl alcohol in the blood were measured on day 1 and in weeks 13 and 26. Maximum mean plasma conc. (Cmax) was observed 2-16 hours after dosing independent of sex, dose level or sampling day. The rate and extent of systemic exposure to dogs as shown by AUC24 and Cmax on day 1 and in weeks 13 and 26 increased with increasing dose level. Increases were less than the proportionate dose increment and there was statistically significant evidence of non-proportionality on each sampling day.

STATISTICAL RESULTS: No statistically significant changes were observed in any of the parameters examined in the main study , the full results were therefore not presented in the publication. Statistical significance for reticulocytes, monocytes, basophils, eosinophils and large unstained cellcounts was not reported as these data were not normally distributed.
Dose descriptor:
NOAEL
Effect level:
>= 2 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects
Critical effects observed:
no
Conclusions:
NOAEL 2000 mg/kg/day (dogs). No adverse effects were seen in this well conducted study at any dose level. Cmax was reached at 2-16 hours post-dosing. Cmax and AUC increased with increasing dose level but the increase was not proportional.
Executive summary:

In a study conducted according to a protocol very similar to OECD guideline 408 using behenylalcohol, a repeated oral dose (26-week) NOAEL of 2000 mg/kg bw/day was determined in beagle dogs. The study was performed in compliance with GLP.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Meets generally accepted scientific standards, well documented and acceptable for assessment.
System:
hepatobiliary
Organ:
liver

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

Subchronic toxicity:

A 90-day study was not available for the test item, however read across data were available from supporting substances (structural analogue or surrogate): Sodium dodecyl sulfate, Sodium laureth sulfate, Behenyl alcohol. For read across substances, two 90-day feeding studies (Sodium dodecyl sulfate, Sodium laureth sulfate) and a 26 weeks feeding study (Behenyl alcohol) were applied in a weight of evidence approach. For behenyl alcohol no adverse effects were seen in a well conducted study at any dose level. Cmax was reached at 2-16 hours post-dosing. The NOAEL was determined to be 1000 mg/kg body weight. Sodium dodecyl sulfate was tested in a 90 day feeding study on rats at dietary levels of 40, 200, 1000 or 5000 ppm (corresponding to 3, 17, 86 or 430 mg/kg bw/day; Walkeret al., 1967). The NOAEL was established at the highest dose level of 5000 ppm (430 mg/kg bw/day). Sodium laureth sulfate (ethoxylation degree of 3) was tested in a 90-day rat diet study at dose levels of 0, 40, 200, 1000 and 5000 ppm active material, corresponding to 0, 2, 10, 50 and 250 mg/kg bw/day (Walker, 1967). The NOAEL was established greater than 250 mg/kg bw/day.

General assessment and conclusion:

For risk characterisation, the NOAEL of 250 mg/kg bw in the 90-day feeding studies with Sodium laureth sulfate (Walker et al., 1967) was selected as most conservative value. Further information supporting the safety of the test substance is provided in the read across justification.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The available repeated dose toxicity studies of the read across substances administered via diet provide a coherent picture on the subchronic oral toxicity of alcohols, alkylsulfates and alkyl ethersulfates and the lowest NOAEL (250 mg/kg bw/d Walker, 1967) was chosen for risk assessment.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification

As there were no relevant findings below classification threshold of 100 mg/kg bw, classification for repeated dose toxicity is not warranted according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008).