Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 284-664-9 | CAS number: 84961-74-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
No studies are available on the reproduction toxicity of LAS IPA. The endpoint was addressed with information from LAS Na and IPA. One three generation study with LAS Na after oral exposure, shows no effects on the reproduction parameters. No OECD 421/422 is available for IPA, but a developmental toxicity (OECD 414) is available. This inhalation study shows no effects on reproduction/fertility.
Link to relevant study records
- Endpoint:
- three-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Unavailable - original study report dated 1971
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- - Principle of test: Three-generation reproductive toxicity study
- Short description of test conditions: Na-LAS (chain length distribution C10-14) was fed for 84 days to 4 groups of weanling rats (3 dose levels, plus control), each dose consisting of 50 animals each of both sexes (PO-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (Fla- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the Flb-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old, and were continued until the F3b generation was weaned. - GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Charles River
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:
- Age at study initiation: (P) weanling; (F1) 21 days
- Weight at study initiation: (P) Males: average 59.4-59.9 g; Females: average 57.0-57.3 g; (F1) Males: group weight 183.5-214.2 g; Females: group weight 157.8-193.2 g
- Housing: individual wire bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 76 +/- 3
- Humidity (%): 50 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12 hrs
: - Route of administration:
- oral: feed
- Vehicle:
- not specified
- Details on mating procedure:
- premating exposure period 84 days
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 2 years ( 3 generations)
- Frequency of treatment:
- continuous in feed
- Details on study schedule:
- - F1 parental animals not mated until 80-85 days old
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: 107-112 days old - Dose / conc.:
- 14 mg/kg bw/day (nominal)
- Remarks:
- corresponding to 0.02% dose level in diet
- Dose / conc.:
- 70 mg/kg bw/day (nominal)
- Remarks:
- corresponding to 0.1% dose level in diet
- Dose / conc.:
- 350 mg/kg bw/day (nominal)
- Remarks:
- corresponding to 0.5% dose level in diet
- No. of animals per sex per dose:
- 50
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Na-LAS (chain length distribution C10-14) was fed for 84 days to 4 groups of weanling rats (3 dose levels, plus control), each dose consisting of 50 animals each of both sexes (P0-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (F1a- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the F1b-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old, and were continued until the F3b generation was weaned.
- Parental animals: Observations and examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Litter observations:
- Deformities and number of pups, average body weights, feed consumption, feed efficiency.
- Postmortem examinations (parental animals):
- Necropsy, body weight, organ to body weight ratios, routine hematology and histology.
- Postmortem examinations (offspring):
- Necropsy, body weight, organ to body weight ratios, routine hematology and histology.
- Reproductive indices:
- fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No effects to average food consumption were noted in the initial twelve weeks
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 350 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- Critical effects observed:
- no
- Clinical signs:
- not specified
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For futher details see "details on results (F1)" section below
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not specified
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 350 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed in sacrfied rats at weaning
- Critical effects observed:
- no
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 350 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed
- Critical effects observed:
- no
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- No significant effects on reproduction were observed at the highest concentration tested. Based on this results the NOAEL (fertility) was determined to be 350 mg/kg bw/day (corresponding to 0.5% test item in diet).
- Executive summary:
In a three-generation reproduction study Na-LAS (chain length distribution C10-14) was administered to 50 Charles River rats/sex/dose indietat dose levels of 0, 0.02%, 0.1% or 0.5% in diet (equivalent to 0, 14, 70 or 350 mg/kg bw/day, respectively) for 84 days (P0-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (F1a- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the F1b-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old and were continued until the F3b generation was weaned.
No significant effects were observed at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was 350 mg/kg bw (corresponding to 0.5% test item in diet).Based on these observations the NOAEL (fertility) was derived at 350 mg/kg bw/d (highest dose tested under the conditions of this study).
- Endpoint:
- three-generation reproductive toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Read-across approach - see read-across justification in section 13.
- Reason / purpose for cross-reference:
- read-across source
- Principles of method if other than guideline:
- - Principle of test: Three-generation reproductive toxicity study
- Short description of test conditions: Na-LAS (chain length distribution C10-14) was fed for 84 days to 4 groups of weanling rats (3 dose levels, plus control), each dose consisting of 50 animals each of both sexes (PO-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (Fla- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the Flb-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old, and were continued until the F3b generation was weaned. - GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Charles River
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:
- Age at study initiation: (P) weanling; (F1) 21 days
- Weight at study initiation: (P) Males: average 59.4-59.9 g; Females: average 57.0-57.3 g; (F1) Males: group weight 183.5-214.2 g; Females: group weight 157.8-193.2 g
- Housing: individual wire bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 76 +/- 3
- Humidity (%): 50 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12 hrs
: - Route of administration:
- oral: feed
- Vehicle:
- not specified
- Details on mating procedure:
- premating exposure period 84 days
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 2 years ( 3 generations)
- Frequency of treatment:
- continuous in feed
- Details on study schedule:
- - F1 parental animals not mated until 80-85 days old
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: 107-112 days old - Dose / conc.:
- 14 mg/kg bw/day (nominal)
- Remarks:
- corresponding to 0.02% dose level in diet
- Dose / conc.:
- 70 mg/kg bw/day (nominal)
- Remarks:
- corresponding to 0.1% dose level in diet
- Dose / conc.:
- 350 mg/kg bw/day (nominal)
- Remarks:
- corresponding to 0.5% dose level in diet
- No. of animals per sex per dose:
- 50
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Na-LAS (chain length distribution C10-14) was fed for 84 days to 4 groups of weanling rats (3 dose levels, plus control), each dose consisting of 50 animals each of both sexes (P0-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (F1a- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the F1b-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old, and were continued until the F3b generation was weaned.
- Parental animals: Observations and examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Litter observations:
- Deformities and number of pups, average body weights, feed consumption, feed efficiency.
- Postmortem examinations (parental animals):
- Necropsy, body weight, organ to body weight ratios, routine hematology and histology.
- Postmortem examinations (offspring):
- Necropsy, body weight, organ to body weight ratios, routine hematology and histology.
- Reproductive indices:
- fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No effects to average food consumption were noted in the initial twelve weeks
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 350 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- Critical effects observed:
- no
- Clinical signs:
- not specified
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For futher details see "details on results (F1)" section below
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not specified
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 350 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed in sacrfied rats at weaning
- Critical effects observed:
- no
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 350 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed
- Critical effects observed:
- no
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- No significant effects on reproduction were observed at the highest concentration tested. Based on this results the NOAEL (fertility) was determined to be 350 mg/kg bw/day (corresponding to 0.5% test item in diet).
- Executive summary:
In a three-generation reproduction study Na-LAS (chain length distribution C10-14) was administered to 50 Charles River rats/sex/dose indietat dose levels of 0, 0.02%, 0.1% or 0.5% in diet (equivalent to 0, 14, 70 or 350 mg/kg bw/day, respectively) for 84 days (P0-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (F1a- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the F1b-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old and were continued until the F3b generation was weaned.
No significant effects were observed at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was 350 mg/kg bw (corresponding to 0.5% test item in diet).Based on these observations the NOAEL (fertility) was derived at 350 mg/kg bw/d (highest dose tested under the conditions of this study).
Referenceopen allclose all
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 350 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Sufficient to address requirements.
Effect on fertility: via inhalation route
- Study duration:
- subacute
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Since no data exist on the reproduction toxicity of LAS IPA, information on LAS Na and IPA were used to assess the reproductive toxicity potential of the substance.
IPA:
No reproduction toxicity is available with IPA; however, one inhalation pre-natal developmental toxicity OECD 414 study (Kier & Thake, 1988). No effects were observed on reproduction parameters. The NOAELs set in the study were only based on systemic toxicity (maternal toxicity) and hence, they are not relevant for this endpoint. No NOAEL for reproductive effects is set.
LAS Na:
LAS Na (C10 -14; CAS 69669 -44 -9) was fed for 84 days to 4 groups of weanling rats for two years (three generations) at doses of 14, 70, 350 mg/kg bw/day. No significant effects were observed even at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was determined to be 350 mg/kg bw/day (0.5%) (Buehler et al., 1971).
Effects on developmental toxicity
Description of key information
Two studies were performed with LAS Na addressing the developmental toxicity potential of the substance after oral exposure. In these studies marginal teratogenic effects were seen at doses of maternal toxicity. The effect was not considered to be a clear-cut developmental effect and it was associated with maternal toxicity.One inhalation teratology study is available with vapours of isopropylamine. No effects were observed on the development of the foetus/offspring (pre- or post-natally) and the NOAELs set in the study were only based on systemic maternal toxicity; hence, they are not relevant for this endpoint. No NOAEL for developmental effects is set.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Unavailable - study report dated 1971
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test: Prenatal developmental toxicity assay in pregnant rats
- Short description of test conditions: After overnight mating, the rats were randomly allocated to five groups which included one control group and four different treatment groups.LAS was prepared daily as a series of graded aqueous solutions. Animals in all groups were dosed orally at the standard volume of 1.0 mL/100 g. Control animals were dosed in a similar manner with distilled water used as the vehicle. The dams were observed daily for signs of toxicity and weighed on days 1, 3, 6, 10, 14, 17 and 20 of pregnancy. On day 20, the rats were killed by CO2 euthanasia.
- Parameters analysed / observed:Ovaries and uterine contents were examined immediately for number of copora lutea, number of viable young, number of resorption sites, litter weight, and fetal abnormalities. - GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Charles River CD strain
- Route of administration:
- oral: drinking water
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- day 6 to day 15 of pregnancy
- Frequency of treatment:
- daily
- Duration of test:
- 20 days
- Dose / conc.:
- 0 other: mg/kg
- Dose / conc.:
- 0.2 other: mg/kg
- Dose / conc.:
- 2 other: mg/kg
- Dose / conc.:
- 300 other: mg/kg
- Dose / conc.:
- 600 other: mg/kg
- No. of animals per sex per dose:
- not specified
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- After overnight mating, the rats were randomly allocated to five groups which included one control group and four different treatment groups. LAS was prepared daily as a series of graded aqueous solutions. Animals in all groups were dosed orally at the standard volume of 1.0 mL/100 g. Control animals were dosed in a similar manner with distilled water used as the vehicle. The dams were observed daily for signs of toxicity and weighed on days 1, 3, 6, 10, 14, 17 and 20 of pregnancy. On day 20, the rats were killed by CO2 euthanasia. Their ovaries and uterine contents were examined immediately for number of corpora lutea, number of viable young, number of resorption sites, litter weight, and fetal abnormalities.
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of early resorptions: Yes / No / No data
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Change in bodyweight was not affected by treatment at 0.2, 2.0, and 300 mg/kg, but treatment at 600 mg/kg was associated with retarded weight gain and a transient diarrhea following initiation of treatment.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Details on results:
- Parent animals were observed daily.Change in bodyweight was not affected by treatment at 0.2, 2.0, and 300 mg/kg, but treatment at 600 mg/kg was associated with retarded weight gain and a transient diarrhea following initiation of treatment
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not examined
- Total litter losses by resorption:
- not examined
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- The pregnancy rate was comparable at all dosages.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 other: mg/kg
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: maternal toxicity
- Remarks:
- retarded weight gain and a transient diarrhea observed at high dose level
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- The distribution of skeletal variants were not statistically significant with the exception of a marginal retardation of sternebral ossification at 600 mg/kg.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- The incidence of minor visceral anomalies was unaffected by treatment at any dosage.
- Details on embryotoxic / teratogenic effects:
- - Pregnancy/litter data: The litter parameters assessed included litter size, fetal loss and litter weight. These parameters were not significantly affected by any dosage. Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg.
- Embryonic and fetal development were assessed by the incidence of major malformations. The incidence of minor visceral anomalies was unaffected by treatment at any dosage. The distribution of skeletal variants were not statistically significant with the exception of a marginal retardation of sternebral ossification at 600 mg/kg. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 other: mg/kg
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- skeletal malformations
- Remarks on result:
- other: teratogenicity
- Remarks:
- marginal retardation of sternebral ossification
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Female rats were given LAS orally in distilled water from gestation days 6 to 15 during pregnancy. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Pregnancy rates were comparable at all doses. Litter parameters were not significantly affected at any dose. No significant differences were observed in visceral anomalies or skeletal variants, with the exception of a marginal retardation of sternabral ossification at the highest dose. Based on these results the maternal and developmental NOAELs were therefore determined to 300 mg/kg.
- Executive summary:
In a developmental toxicity study LAS was administrated pregnant Charles River CD rats/does in water at dose levels of 0, 0.2, 2, 300 or 600 mg/kg from days 6 through 15 of gestation. The number of animals tested was not specified in the study.
The parent animals were observed daily. Body weight change was not affected by treatment at 0.2, 2.0 and 300 mg/kg, but treatment at 600 mg/kg was associated with delayed weight gain and transient diarrhoea after the start of treatment. Pregnancy rates were comparable at all doses. Litter parameters evaluated were litter size, fetal loss and litter weight. These parameters were not significantly affected by any of the doses. Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg. In addition, embryonic and fetal development was assessed by the incidence of major malformations. The incidence of minor visceral anomalies was not affected by the treatment at any dose. The distribution of skeletal variants was not statistically significant except for a marginal delay in sternal ossification at 600 mg/kg. Based on these observations the maternal and the developmental NOAELs are therefore determined to be 300 mg/kg.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Unavailable - publication dated 1975
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Twenty female mice were administered 0.2, 2.0, 300 or 600 mg/kg bw of LAS by gavage at days 6-15 of gestation. All animals were sacrificed on day 17 of pregnancy.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Housing: In plastic containers
- Diet: ad libitum
- Water: ad libitum (Spratt's Laboratory Diet No. 1)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50 ± 5% relative humidity - Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on exposure:
- Dosing commenced on day 6 after confirmation of mating by detection of the vaginal plug.
Exposure continued until day 15 of gestation. - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Male and female mice were housed five per cage in opaque plastic cages until natural mating occurred.
- Duration of treatment / exposure:
- days 6 - 15 of pregnancy
- Frequency of treatment:
- daily
- Duration of test:
- sacrifice at day 17 of pregnancy
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- 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:
- 20 females
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Two doses were chosen to form the basis for safety evaluation (0.2 and 2.0 mg/kg bw/day) because the likely maximum human intake of detergent from ordinary kitchen use has been estimated at 0.14 mg/kg bw/day, thus providing factors of 1-2 times the human exposure level. Two further doses were also investigated (300 and 600 mg/kg bw/day) based on previous toxicity data suggesting that these would impair maternal survival and result in obvious adverse effects.
- Maternal examinations:
- All animals were observed daily for signs of malreaction and were weighed regularly throughout gestation. All animals that died, and survivors at termination, were dissected and examined for macroscopic changes.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: All animals were weighed regularly throughout gestation
POST-MORTEM EXAMINATIONS: Yes
All animals that died, and survivors at termination, were dissected and examined for macroscopic changes.
- Ovaries and uterine content:
- The ovaries was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantation: Yes
: - Fetal examinations:
- - External examinations: Yes
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Treatment at 300 and 600 mg/kg bw/day was associated with increased mortality (35% and 90% respectively).
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At 300 mg/kg bw/day weight gain was retarded only during the first four days. No assessment could be made at 600 mg/kg bw/day, due to the high mortality rate.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Necropsy revealed an ubiquitous occurrence of tympanites, sometimes associated with gastritis.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Number of abortions:
- not examined
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- Among parent animals, treatment at 300 and 600 mg/kg bw/day was associated with increased mortality (35% and 90% respectively).At 300 mg/kg bw/day weight gain was retarded only during the first four days. No assessment could be made at 600 mg/kg bw/day, due to the high mortality rate.Necropsy revealed an ubiquitous occurrence of tympanites, sometimes associated with gastritis. Pregnancy rate was essentially comparable for all groups.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 2 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- mortality
- Remarks on result:
- other: maternal toxicity
- Remarks:
- increased mortality at 300 and 600 mg/kg bw/day.
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the 300 mg/kg bw/day dose, the incidence of total litter loss was 20%; this was attributed to the high maternal toxicity observed at this dose.
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For further details see "details on embryotoxic / teratogenic effects" section below.
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Minor anomalies, including gross anomalies were increased.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Minor anomalies, including skeletal anomalies were increased.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Minor anomalies, including visceral anomalies were increased.
- Details on embryotoxic / teratogenic effects:
- At doses with no maternal toxicity (0.2 and 2.0 mg/kg bw/day), no differences were observed among the dose group and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations and post implantation embryonic loss.At these doses the incidences of major malformations and minor abnormalities were not affected.
At the 300 mg/kg bw/day dose, the incidence of total liter loss was 20%; this was attributed to the high maternal toxicity observed at this dose.Among the nine animals with viable young at this dose, mean litter parameters, including litter size and fetal loss, and incidence of major malformations were not statistically different from controls. Minor anomilies, including gross or visceral and skeletal anomalies were increased. At 600 mg/kg there were no live births due to the high maternal mortality rate at this dose. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- skeletal malformations
- visceral malformations
- Remarks on result:
- other: Since, there were no live fetuses at 600 mg/kg bw/day due to the high maternal mortality rate, 300 mg/kg bw/day was considered as the highest dose tested.
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Pregnant female mice were exposed to LAS via gavage on days 6 -15 of gestation. Increased mortality was observed at the two highest doses (300 and 600 mg/kg bw/day). These doses also exhibited retarded weight gain and adverse signs in the necropsy. Pregnancy rate was comparable, however, for all groups. At doses without maternal toxicity, no differences were observed in any parameters. Based on these observations the maternal NOAEL is 2 mg/kg bw/day, however because of the very wide range between the 2 mg/kg and 300 mg/kg bw/day doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative. The NOAEL for teratogenicity is considered to 300 mg/kg bw/day.
- Executive summary:
In a developmental toxicity study LAS was administrated to 20 pregnant CD-1 mice/does by gavage at dose levels of 0, 0.2, 2, 300 or 600 mg/kg bw/day from days 6 through 15 of gestation. All animals were sacrificed on day 17 of gestation.
Among parent animals, treatment at 300 and 600 mg/kg bw/day was associated with increased mortality (35% and 90% respectively). At 300 mg/kg bw/day weight gain was retarded only during the first four days. No assessment could be made at 600 mg/kg bw/day, due to the high mortality rate. Necropsy revealed an ubiquitous occurrence of tympanites, sometimes associated with gastritis. However, pregnancy rate was essentially comparable for all groups. Based on these observations the maternal NOAEL is 2 mg/kg bw/day, because of the very wide range between the 2 mg/kg and 300 mg/kg bw/day doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative.
At doses without maternal toxicity (0.2 and 2.0 mg/kg bw/day), no treatment-related effects on developmental parameters were observed in the treated and control groups. These parameters included number of litters, viable young, litter weight, fetal weight, embryonic deaths, implantation and post-implantation embryonic losses. At these doses the incidences of major malformations and minor abnormalities were also not affected. At 300 mg/kg bw/day, the incidence of total litter loss was 20%; this was attributed to the high maternal toxicity observed at this dose. Among the nine animals with viable pups at 300 mg/kg bw/day, mean litter parameters, including litter size and fetal loss, and the incidence of major malformations were not statistically different from controls. Minor anomalies, including gross or visceral and skeletal anomalies, were increased. At 600 mg/kg there were no live births due to the high maternal mortality rate at this dose. Therefore, based on these observations the developmental NOAEL is 300 mg/kg bw/day.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Read-across approach - see read-across justification in section 13.
- Reason / purpose for cross-reference:
- read-across source
- Principles of method if other than guideline:
- - Principle of test: Prenatal developmental toxicity assay in pregnant rats
- Short description of test conditions: After overnight mating, the rats were randomly allocated to five groups which included one control group and four different treatment groups.LAS was prepared daily as a series of graded aqueous solutions. Animals in all groups were dosed orally at the standard volume of 1.0 mL/100 g. Control animals were dosed in a similar manner with distilled water used as the vehicle. The dams were observed daily for signs of toxicity and weighed on days 1, 3, 6, 10, 14, 17 and 20 of pregnancy. On day 20, the rats were killed by CO2 euthanasia.
- Parameters analysed / observed:Ovaries and uterine contents were examined immediately for number of copora lutea, number of viable young, number of resorption sites, litter weight, and fetal abnormalities. - GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Charles River CD strain
- Route of administration:
- oral: drinking water
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- day 6 to day 15 of pregnancy
- Frequency of treatment:
- daily
- Duration of test:
- 20 days
- Dose / conc.:
- 0 other: mg/kg
- Dose / conc.:
- 0.2 other: mg/kg
- Dose / conc.:
- 2 other: mg/kg
- Dose / conc.:
- 300 other: mg/kg
- Dose / conc.:
- 600 other: mg/kg
- No. of animals per sex per dose:
- not specified
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- After overnight mating, the rats were randomly allocated to five groups which included one control group and four different treatment groups. LAS was prepared daily as a series of graded aqueous solutions. Animals in all groups were dosed orally at the standard volume of 1.0 mL/100 g. Control animals were dosed in a similar manner with distilled water used as the vehicle. The dams were observed daily for signs of toxicity and weighed on days 1, 3, 6, 10, 14, 17 and 20 of pregnancy. On day 20, the rats were killed by CO2 euthanasia. Their ovaries and uterine contents were examined immediately for number of corpora lutea, number of viable young, number of resorption sites, litter weight, and fetal abnormalities.
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of early resorptions: Yes / No / No data
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Change in bodyweight was not affected by treatment at 0.2, 2.0, and 300 mg/kg, but treatment at 600 mg/kg was associated with retarded weight gain and a transient diarrhea following initiation of treatment.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Details on results:
- Parent animals were observed daily.Change in bodyweight was not affected by treatment at 0.2, 2.0, and 300 mg/kg, but treatment at 600 mg/kg was associated with retarded weight gain and a transient diarrhea following initiation of treatment
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not examined
- Total litter losses by resorption:
- not examined
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- The pregnancy rate was comparable at all dosages.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 other: mg/kg
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: maternal toxicity
- Remarks:
- retarded weight gain and a transient diarrhea observed at high dose level
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- The distribution of skeletal variants were not statistically significant with the exception of a marginal retardation of sternebral ossification at 600 mg/kg.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- The incidence of minor visceral anomalies was unaffected by treatment at any dosage.
- Details on embryotoxic / teratogenic effects:
- - Pregnancy/litter data: The litter parameters assessed included litter size, fetal loss and litter weight. These parameters were not significantly affected by any dosage. Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg.
- Embryonic and fetal development were assessed by the incidence of major malformations. The incidence of minor visceral anomalies was unaffected by treatment at any dosage. The distribution of skeletal variants were not statistically significant with the exception of a marginal retardation of sternebral ossification at 600 mg/kg. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 other: mg/kg
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- skeletal malformations
- Remarks on result:
- other: teratogenicity
- Remarks:
- marginal retardation of sternebral ossification
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Female rats were given LAS orally in distilled water from gestation days 6 to 15 during pregnancy. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Pregnancy rates were comparable at all doses. Litter parameters were not significantly affected at any dose. No significant differences were observed in visceral anomalies or skeletal variants, with the exception of a marginal retardation of sternabral ossification at the highest dose. Based on these results the maternal and developmental NOAELs were therefore determined to 300 mg/kg.
- Executive summary:
In a developmental toxicity study LAS was administrated pregnant Charles River CD rats/does in water at dose levels of 0, 0.2, 2, 300 or 600 mg/kg from days 6 through 15 of gestation. The number of animals tested was not specified in the study.
The parent animals were observed daily. Body weight change was not affected by treatment at 0.2, 2.0 and 300 mg/kg, but treatment at 600 mg/kg was associated with delayed weight gain and transient diarrhoea after the start of treatment. Pregnancy rates were comparable at all doses. Litter parameters evaluated were litter size, fetal loss and litter weight. These parameters were not significantly affected by any of the doses. Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg. In addition, embryonic and fetal development was assessed by the incidence of major malformations. The incidence of minor visceral anomalies was not affected by the treatment at any dose. The distribution of skeletal variants was not statistically significant except for a marginal delay in sternal ossification at 600 mg/kg. Based on these observations the maternal and the developmental NOAELs are therefore determined to be 300 mg/kg.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Read-across approach - see read-across justification in section 13.
- Reason / purpose for cross-reference:
- read-across source
- Principles of method if other than guideline:
- Twenty female mice were administered 0.2, 2.0, 300 or 600 mg/kg bw of LAS by gavage at days 6-15 of gestation. All animals were sacrificed on day 17 of pregnancy.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Housing: In plastic containers
- Diet: ad libitum
- Water: ad libitum (Spratt's Laboratory Diet No. 1)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50 ± 5% relative humidity - Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on exposure:
- Dosing commenced on day 6 after confirmation of mating by detection of the vaginal plug.
Exposure continued until day 15 of gestation. - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Male and female mice were housed five per cage in opaque plastic cages until natural mating occurred.
- Duration of treatment / exposure:
- days 6 - 15 of pregnancy
- Frequency of treatment:
- daily
- Duration of test:
- sacrifice at day 17 of pregnancy
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- 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:
- 20 females
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Two doses were chosen to form the basis for safety evaluation (0.2 and 2.0 mg/kg bw/day) because the likely maximum human intake of detergent from ordinary kitchen use has been estimated at 0.14 mg/kg bw/day, thus providing factors of 1-2 times the human exposure level. Two further doses were also investigated (300 and 600 mg/kg bw/day) based on previous toxicity data suggesting that these would impair maternal survival and result in obvious adverse effects.
- Maternal examinations:
- All animals were observed daily for signs of malreaction and were weighed regularly throughout gestation. All animals that died, and survivors at termination, were dissected and examined for macroscopic changes.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: All animals were weighed regularly throughout gestation
POST-MORTEM EXAMINATIONS: Yes
All animals that died, and survivors at termination, were dissected and examined for macroscopic changes.
- Ovaries and uterine content:
- The ovaries was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantation: Yes
: - Fetal examinations:
- - External examinations: Yes
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Treatment at 300 and 600 mg/kg bw/day was associated with increased mortality (35% and 90% respectively).
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At 300 mg/kg bw/day weight gain was retarded only during the first four days. No assessment could be made at 600 mg/kg bw/day, due to the high mortality rate.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Necropsy revealed an ubiquitous occurrence of tympanites, sometimes associated with gastritis.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Number of abortions:
- not examined
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- Among parent animals, treatment at 300 and 600 mg/kg bw/day was associated with increased mortality (35% and 90% respectively).At 300 mg/kg bw/day weight gain was retarded only during the first four days. No assessment could be made at 600 mg/kg bw/day, due to the high mortality rate.Necropsy revealed an ubiquitous occurrence of tympanites, sometimes associated with gastritis. Pregnancy rate was essentially comparable for all groups.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 2 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- mortality
- Remarks on result:
- other: maternal toxicity
- Remarks:
- increased mortality at 300 and 600 mg/kg bw/day.
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At the 300 mg/kg bw/day dose, the incidence of total litter loss was 20%; this was attributed to the high maternal toxicity observed at this dose.
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For further details see "details on embryotoxic / teratogenic effects" section below.
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Minor anomalies, including gross anomalies were increased.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Minor anomalies, including skeletal anomalies were increased.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Minor anomalies, including visceral anomalies were increased.
- Details on embryotoxic / teratogenic effects:
- At doses with no maternal toxicity (0.2 and 2.0 mg/kg bw/day), no differences were observed among the dose group and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations and post implantation embryonic loss.At these doses the incidences of major malformations and minor abnormalities were not affected.
At the 300 mg/kg bw/day dose, the incidence of total liter loss was 20%; this was attributed to the high maternal toxicity observed at this dose.Among the nine animals with viable young at this dose, mean litter parameters, including litter size and fetal loss, and incidence of major malformations were not statistically different from controls. Minor anomilies, including gross or visceral and skeletal anomalies were increased. At 600 mg/kg there were no live births due to the high maternal mortality rate at this dose. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- skeletal malformations
- visceral malformations
- Remarks on result:
- other: Since, there were no live fetuses at 600 mg/kg bw/day due to the high maternal mortality rate, 300 mg/kg bw/day was considered as the highest dose tested.
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Pregnant female mice were exposed to LAS via gavage on days 6 -15 of gestation. Increased mortality was observed at the two highest doses (300 and 600 mg/kg bw/day). These doses also exhibited retarded weight gain and adverse signs in the necropsy. Pregnancy rate was comparable, however, for all groups. At doses without maternal toxicity, no differences were observed in any parameters. Based on these observations the maternal NOAEL is 2 mg/kg bw/day, however because of the very wide range between the 2 mg/kg and 300 mg/kg bw/day doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative. The NOAEL for teratogenicity is considered to 300 mg/kg bw/day.
- Executive summary:
In a developmental toxicity study LAS was administrated to 20 pregnant CD-1 mice/does by gavage at dose levels of 0, 0.2, 2, 300 or 600 mg/kg bw/day from days 6 through 15 of gestation. All animals were sacrificed on day 17 of gestation.
Among parent animals, treatment at 300 and 600 mg/kg bw/day was associated with increased mortality (35% and 90% respectively). At 300 mg/kg bw/day weight gain was retarded only during the first four days. No assessment could be made at 600 mg/kg bw/day, due to the high mortality rate. Necropsy revealed an ubiquitous occurrence of tympanites, sometimes associated with gastritis. However, pregnancy rate was essentially comparable for all groups. Based on these observations the maternal NOAEL is 2 mg/kg bw/day, because of the very wide range between the 2 mg/kg and 300 mg/kg bw/day doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative.
At doses without maternal toxicity (0.2 and 2.0 mg/kg bw/day), no treatment-related effects on developmental parameters were observed in the treated and control groups. These parameters included number of litters, viable young, litter weight, fetal weight, embryonic deaths, implantation and post-implantation embryonic losses. At these doses the incidences of major malformations and minor abnormalities were also not affected. At 300 mg/kg bw/day, the incidence of total litter loss was 20%; this was attributed to the high maternal toxicity observed at this dose. Among the nine animals with viable pups at 300 mg/kg bw/day, mean litter parameters, including litter size and fetal loss, and the incidence of major malformations were not statistically different from controls. Minor anomalies, including gross or visceral and skeletal anomalies, were increased. At 600 mg/kg there were no live births due to the high maternal mortality rate at this dose. Therefore, based on these observations the developmental NOAEL is 300 mg/kg bw/day.
Referenceopen allclose all
The maternal NOAEL of 2 mg/kg bw d is considered very conservative because the range (2-300 mg/kg bw/day) was too wide, especially considering the repeated dose toxicity studies (section 7.5.1) which give much higher NOAEL values.
The maternal NOAEL of 2 mg/kg bw d is considered very conservative because the range (2-300 mg/kg bw/day) was too wide, especially considering the repeated dose toxicity studies (section 7.5.1) which give much higher NOAEL values.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Sufficient to address requirements
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No data exist on the developmental toxicity of LAS IPA, therefore, information on LAS Na and IPA were used to address this requirement.
IPA:
In a GLP, similar to Guidelines study (Kier & Thake, 1988) female rats were exposed to IPA vapours, whole body, during gestation, at concentrations of 50, 499 or 1000 mg IPA/m3. The substance did not induce embryotoxic, fetotoxic or teratogenic effects, although slight maternal toxicity was observed at the 499 mg/m3 exposure level and substantial maternal toxicity was observed at 1000 mg/m3.
LAS Na:
Pregnant female mice were exposed to LAS via gavage on days 6 -15 of gestation. Increased mortality was observed at the two highest doses (300 and 600 mg/kg bw/day). These doses also exhibited retarded weight gain and adverse signs in the necropsy. Pregnancy was comparable, however, for all groups. At doses without maternal toxicity, no differences were observed in any parameters. Because of the very wide range between the 2 mg/kg and 300 mg/kg doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative. The NOAEL for teratogenicity was 300 mg/kg bw/day (Palmer et al., 1971)
Pregnant female rats were given LAS orally in distilled water from gestation days 6 to 15 at doses of 0.2, 2, 300, 600 mg/kg bw/day. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Pregnancy rates were comparable at all doses. Litter parameters were not significantly affected at any dose. No significant differences were observed in visceral anomalies or skeletal variants, with the exception of a marginal retardation of sternabral ossification at the highest dose. The NOAEL was set at 300 mg/kg bw/day both for maternal toxicity and teratogenicity (Palmer et al., 1975).
Based on the results of the aforementioned studies LAS IPA is not considered to be a developmental toxicant.
Justification for selection of Effect on developmental
toxicity: via oral route:
Only studies with LAS Na are available via the oral route. In these
studies marginal teratogenic effects were seen at doses of maternal
toxicity. The effect was not considered to be a clear-cut developmental
effect and it was associated with maternal toxicity. No NOAEL for
developmental effects is set.
Justification for selection of Effect on developmental toxicity: via
inhalation route:
One inhalation study is available with vapours of isopropylamine. No
effects were observed on the development of the foetus/offspring (pre-
or post-natally) and the NOAELs set in the study were only based on
systemic maternal toxicity; hence, they are not relevant for this
endpoint. No NOAEL for developmental effects is set.
Justification for classification or non-classification
Based on the available data, for LAS Na and IPA, LAS IPA does not need to be classified for effects on fertility and developmental toxicity according to Regulation (EC) No. 1272/2008.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

EU Privacy Disclaimer
This website uses cookies to ensure you get the best experience on our websites.