Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because a pre-natal developmental toxicity study is available
other:
Reproductive effects observed:
not specified
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
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A reproductive toxicity study was not available for the test item, however read across data were available from supporting substances (structural analogue or surrogate): Sodium dodecyl sulfate and behenyl alcohol. For read across substances, repeated dose toxicity, reproductive and developmental toxicity studies were applied in a weight of evidence approach.

A reproductive toxicity study with behenyl alcohol is available. Rats were administered 0, 10 00, or 1000 mg /kg bw/day by gavage. Males were treated daily for 71 days prior to mating, during mating, and until termination. Females were treated with the test

substance for 15 days prior to mating, during mating, and up to Day 17 of gestation. No maternal toxicity or reproductive toxicity was observed. Hence, the NOAEL was 1000 mg/kg bw/day for both parental and fetal toxicity. Behenyl alcohol was administered to New Zealand white rabbits at 0, 125, 500, or 2000 mg /kg bw/day by gavage daily from Day 6 to Day 19 of gestation. Females were sacrificed on Day 29 and their uterine contents were examined. Based on the absence of maternal and developmental toxicity under the conditions of this study, the NOAEL was 2000 mg/kg bw/day, the highest dose tested. Two developmental toxicity studies are available with sodium lauryl sulfate. The test substance was administered orally by gavage at dose levels of 0, 0.2, 2, 300 and 600 mg/kg bw/day once daily from Day 6 to Day 15 of gestation for rats and Day 19 of gestation for rabbits, respectively. The NOAEL within these studies were established at 300 mg/kg bw/d for maternal toxicity and greater 600 mg/kg bw/d for developmental toxicity for rat and rabbits, respectively. 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. Also oral gavage of fatty alcohol did not result in any signs of systemic toxicity within the reproduction toxicity studies. However application of sodium lauryl sulfate via gavage resulted in maternal toxicity. This maternal toxicity may be related to local irritation, as shorter chained alkyl sulfates are known to have irritating properties. To cover the uncertainties which may occur due to the read across the lowest NOAEL (250 mg/kg bw/d Walker, 1967) was chosen for risk assessment.


Short description of key information:
Alcohol compenents of test item showed no adverse effect on reproductive organs. No adverse effects on reproductive organs and tissue was observed in repeated dose studies of alkylsulfates (sodium lauryl sulfate) and alkylethersulfates (sodium laureth sulfate).

Justification for selection of Effect on fertility via oral route:
Read across substances showed no adverse effects on reproductive organs and tissue in repeated dose and developmental toxicity studies of alkylsulfates (sodium lauryl sulfate) and behenyl alcohol. To cover the uncertainties which may occur due to the read across the lowest NOAEL (repeated dose toxicity, 250 mg/kg bw/d Walker, 1967) was chosen for risk assessment.

Effects on developmental toxicity

Link to relevant study records
Reference
Endpoint:
developmental toxicity
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 alkylsulfates contained in registered substance - see attached read across justification.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
lack of details on test substance, intervals in dose range
GLP compliance:
no
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
According to guideline.
Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
no
Details on mating procedure:
According to guideline.
Duration of treatment / exposure:
Day 6-18
Frequency of treatment:
daily
Duration of test:
Day 1-29
Dose / conc.:
0.2 mg/kg bw/day (nominal)
Dose / conc.:
2 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
Dose / conc.:
600 mg/kg bw/day (nominal)
No. of animals per sex per dose:
13
Control animals:
yes, concurrent vehicle
Maternal examinations:
According to guideline.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: No data
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No
Statistics:
Yes
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity in the form of anorexia, weight loss, cachexia, death and abortion (and/or total resorption) was evident in rabbits and mice with AS 600 mg/kg. At dosages that were either non-toxic or only slightly to moderately toxic to the dam, litter parameters were essentially unaffected.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity in the form of anorexia, weight loss, cachexia, death and abortion (and/or total resorption) was evident in rabbits and mice with AS 600 mg/kg.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity in the form of anorexia, weight loss, cachexia, death and abortion (and/or total resorption) was evident in rabbits and mice with AS 600 mg/kg.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity in the form of anorexia, weight loss, cachexia, death and abortion (and/or total resorption) was evident in rabbits and mice with AS 600 mg/kg.
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity in the form of anorexia, weight loss, cachexia, death and abortion (and/or total resorption) was evident in rabbits and mice with AS 600 mg/kg.
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not examined
Number of abortions:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity in the form of anorexia, weight loss, cachexia, death and abortion (and/or total resorption) was evident in rabbits and mice with AS 600 mg/kg.
Pre- and post-implantation loss:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity in the form of anorexia, weight loss, cachexia, death and abortion (and/or total resorption) was evident in rabbits and mice with AS 600 mg/kg.
Total litter losses by resorption:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity in the form of anorexia, weight loss, cachexia, death and abortion (and/or total resorption) was evident in rabbits and mice with AS 600 mg/kg.
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
Maternal toxic effects:yes
Key result
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
clinical signs
other: maternal toxicity
Dose descriptor:
LOAEL
Effect level:
600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
clinical signs
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects
Dose descriptor:
NOAEL
Effect level:
> 600 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: teratogenicity
Abnormalities:
no effects observed
Developmental effects observed:
not specified
Conclusions:
No maternal toxicity and no developmental toxicity up to 300 and 600 mg/kg/day was reported for sodium lauryl sulfate, respectively.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subchronic
Species:
rat
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

A developmental toxicity study was not available for the test item, however read across data were available from supporting substances (structural analogue or surrogate): Sodium dodecyl sulfate and behenyl alcohol. For read across substances, two studies (Sodium dodecyl sulfate, behenyl alcohol) were applied in a weight of evidence approach.

Behenyl alcohol was administered to New Zealand white rabbits at 0, 125, 500, or 2000 mg /kg bw/day by gavage daily from Day 6 to Day 19 of gestation. Females were sacrificed on Day 29 and their uterine contents were examined. Based on the absence of maternal and developmental toxicity under the conditions of this study, the NOAEL was 2000 mg/kg bw/day, the highest dose tested. Two developmental toxicity studies are available with sodium lauryl sulfate. The test substance was administered orally by gavage at dose levels of 0, 0.2, 2, 300 and 600 mg/kg bw/day once daily from Day 6 to Day 15 of gestation for rats and Day 19 of gestation for rabbits, respectively. The NOAEL within these studies were established at 300 mg/kg bw/d for maternal toxicity and greater 600 mg/kg bw/d for developmental toxicity for rat and rabbits, respectively. 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. Also oral gavage of fatty alcohol did not result in any signs of systemic toxicity within the reproduction toxicity studies. However application of sodium lauryl sulfate via gavage resulted in maternal toxicity. This maternal toxicity may be related to local irritation, as shorter chained alkyl sulfates are known to have irritating properties. To cover the uncertainties which may occur due to the read across the lowest NOAEL (250 mg/kg bw/d Walker, 1967) was chosen for risk assessment.

The justification to use read-across data from supporting substances is provided in Section 13 of the IUCLID dossier.


Justification for selection of Effect on developmental toxicity: via oral route:
Read across substances showed no adverse effects on reproductive organs and tissue in repeated dose and developmental toxicity studies of alkylsulfates (sodium lauryl sulfate) and behenyl alcohol. However application of sodium lauryl sulfate via gavage resulted in maternal toxicity. his maternal toxicity may be related to local irritation, as shorter chained alkyl sulfates are known to have irritating properties.

Justification for classification or non-classification

Based on these results and according to the EC Directive (No.93/21/EEC) and CLP Regulation (EC) No. 1272/2008, the test item does not have to be classified and has no obligatory labelling requirement for reproductive and developmental toxicity.

Additional information