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EC number: 701-015-1 | CAS number: 2156592-72-0
- Life Cycle description
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- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
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- Particle size distribution (Granulometry)
- Vapour pressure
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- Additional physico-chemical properties of nanomaterials
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- Endpoint summary
- Stability
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- 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
There is no reproductive toxicity study with the target substance available. Data generated with the category substances LAB and LABS Na were considered pivotal to this endpoint. The target substance is considered to have a parental NOAEL of 50 mg/kg/day and an NOAEL for offspring of 50 mg/kg/day.
Link to relevant study records
- Endpoint:
- two-generation reproductive toxicity
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP study published in peer-reviewed journal.
- Justification for type of information:
- Category Approach; test material is reference substance LAB. The justification for the read across category approach is included in the IU section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Version / remarks:
- EPA/TSCA
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Housing: wire mesh cages
- Diet (e.g. ad libitum): Ralson Purina commercial laboratory feed, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-79
- Humidity (%): 17-76
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: 7 nights, if female was still not pregnant, she was moved to another male for an additional 7 nights, and then to a third male if needed
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): individually - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- daily
- Frequency of treatment:
- F0: Treatment was started 10 weeks before mating. For males, dosing continued for 2 weeks after mating (total of 105 days). For females, dosing continued through lactation for a total of 127 treatment days.
F1: The F1 generation was treated similarly to the F0 generation, but were exposed beginning 11 weeks pre-mating. - Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 30 animals of each sex per dose
- Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: males - weekly, females - weekly before mating, days 0, 7, 14, and 20 of gestation, and days 0, 4, 14, and 21 of lactation
FOOD CONSUMPTION: weekly
- Litter observations:
- STANDARDISATION OF LITTERS
F1 pups were selected for mating at weaning, at least one pup per litter was selected for the adult F1 generation
PARAMETERS EXAMINED
The following parameters were examined in F1 and F2 offspring:
number and sex of pups on days 0, 4, 7, 14, and 21 of lactation, postnatal mortality and presence of gross anomalies daily, weights on days 0, 4, 7, 14, and 21 of lactation
GROSS EXAMINATION OF DEAD PUPS:
yes - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals 2 weeks after mating.
- Maternal animals: All surviving animals at weaning.
GROSS NECROPSY
- Gross necropsy consisted of examination for gross lesions
HISTOPATHOLOGY / ORGAN WEIGHTS
pituitary glands, testes and epididymides, prostate and seminal vesicles, vagina, uterus, ovaries, and gross lesions - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at weaning.
- These animals were subjected to postmortem examinations similar to parental animals above. - Reproductive indices:
- mating index, pregnancy rate, fertility index
- Offspring viability indices:
- pup survival
- Clinical signs:
- effects observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Reproductive performance:
- effects observed, treatment-related
- Dose descriptor:
- NOEL
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Maternal and paternal general toxicity was reduced weight gain in the high dose group. Reduced litter size in the high dose group.
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Reduced survival and weight gain in high dose group. Sporadic occurrences at mid dose level.
- Dose descriptor:
- NOEL
- Generation:
- F2
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Reduced survival and weight gain in the high dose group. Sporadic occurrences at mid dose level.
- Reproductive effects observed:
- not specified
- Conclusions:
- There is no reproductive toxicity study with the target substance available. Data generated with the category substances LAB were considered pivotal to this endpoint. The target substance is considered to have a parental NOAEL of 50 mg/kg/day and an NOAEL for offspring of 50 mg/kg/day.
- Executive summary:
This study examined the effects of exposure to the test substance on reproduction. Groups of 30 female and 30 male rats were exposed to concentrations of 0, 5, 50 and 500 mg/kg day of test substance by oral gavage beginning ten weeks before mating. Animals were then mated. The resulting generation was also exposed to the test substance and mated. Exposure continued through the mating period, and in females through the gestation and lactational periods. All animals were sacrificed and necropsied after exposure. Pups not used for mating were sacrificed at weaning. During the study, animals were observed for clinical signs, mortality, and body weight. Pups were examined for viability and body weight gain. Reproductive indices were also calculated. The NOAEL for parental toxicity was 50 mg/kg/day and the LOAEL was 500 mg/kg/day based on reduced weight gain and litter size in the high dose group. The NOAEL for offspring was 50 mg/kg/day based on reduced body weight gain and survival in the high and mid-dose groups. The LOAEL for offspring was 50 mg/kg/day.
- Endpoint:
- three-generation reproductive toxicity
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well documented peer-reviewed publication.
- Justification for type of information:
- Category Approach; test material is reference substance LABS Na Salt. The justification for the read across category approach is included in the IU section 13.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Principles of method if other than guideline:
- 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:
- other: LAS was administered in feed (Purina Laboratory Meal) - no documentation of dilution prior to addition to meal
- 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 - Remarks:
- Doses / Concentrations:
0.02, 0.1, 0.5% (14, 70, 350 mg/kg bw d)
Basis:
actual ingested - No. of animals per sex per dose:
- 50 males and 50 females per group.
- Control animals:
- yes, concurrent no treatment
- 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
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- no effects to body weight were noted in the initial twelve weeks
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- no effects to body weight were noted in the initial twelve weeks
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- Test substance intake: no effects to average food consumption were noted in the initial twelve weeks
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 350 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: 0.5%
- Clinical signs:
- not specified
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 350 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: 0.5%
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 350 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: 0.5%
- Reproductive effects observed:
- not specified
- Conclusions:
- No significant effects on reproduction were observed at the highest concentration tested.
- Executive summary:
Na-LAS was fed for 84 days to 4 groups of weanling rats for two years (three generations). 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 (0.5%)
Referenceopen allclose all
No mortality attributed to treatment was observed.
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Mean body weights of high-dose-group (500 mg/kg bw/d) males were significantly and consistently reduced {12 = 0.01) in the FO (since premating week); mean body weights of high-dose females were significantly decreased in the FO generation since the 9th week of premating until the first week of lactation (p = 0.05); body weight reduction was significant on day 20 of gestation in both generations (p = 0.01
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
Mating, pregnancy and fertility rates were not influenced.
GROSS PATHOLOGY (PARENTAL ANIMALS)
No gross postmortem findings.
HISTOPATHOLOGY (PARENTAL ANIMALS)
No histopathological findings.
Litter size: Fl and F2 : significant decrease at 500 mg/kg bw/d (p = 0.05 and 0.01 respectively);
pup viability index at birth: Fl: significant decrease at 50 and 500 mg/kg bd/d (p = 0.05) F2: significant decrease at 500 mg/kg bw/d (p = 0.05), since effects at 50 mg/kg bw/d was only noted in a single generation, these effects were not considered biologically significant; survival of pups at day 4 was significantly decreased at 500 mg/kg bw/d in the Fl and F2 litters; survival of pups at day 21 (related to day 4) was significantly decreased only in the F2 litter at 50 mg/kg bw/d (p = 0.05), since effects at 50 mg/kg bw/d was only noted in a single generation, these effects were not considered biologically significant
BODY WEIGHT (OFFSPRING)
mean pup weight:
Fl litters; significant reduction at 50 and 500 mg/kg bw/d at day 7 and only at 500 mg/kg bw/d at day 14 and 21 (p = 0.05), since the reduction in the 50 mg/kg bw/d group was only noted at day 7 and only in the F1 generation, this effect was not considered biologically significant
F2 litters: significant reduction at 500 mg/kg bw/d at day 14 and 21 (p = 0.05).
OTHER FINDINGS (OFFSPRING)
In the high-dose-group, gestation length was significantly increased for the F2 litter interval (22.4 d compared to 22.0 in controls).
Litter Size and Pup Survival Indices
Dose (mg/kg/day) |
Litter size (mean) |
Pup viability index at birth (%) |
Pup survival days 0-4 (%) |
Pup survival days 0-4 (%)1 |
Pup survival days 4-21 (%) |
F1 litters |
|||||
0 |
12.7 |
99.1 |
93.8 |
95.7 |
|
5 |
12.8 |
98.0 |
93.4 |
91.0 |
|
50 |
13.1 |
95.4 |
92.3 |
84.2 |
|
500 |
10.0 |
95.4 |
85.0 |
94.7 |
|
F2 litters |
|||||
0 |
11.3 |
98.6 |
80.2 |
93.5 |
98.1 |
5 |
11.6 |
98.2 |
87.3 |
94.4 |
97.1 |
50 |
13.1 |
97.3 |
89.5 |
92.3 |
89.1 |
500 |
7.0 |
89.0 |
84.1 |
85.9 |
97.3 |
1Excludes data for litters in which all pups died during the Day 0-3 interval.
Mean Pup Weights (g)
Dose (mg/kg/day) |
Day 0 |
Day 4- Precull |
Day 4- Postcull |
Day 7 |
Day 14 |
Day 21 |
F1 litters |
||||||
0 |
6.0 |
8.4 |
8.4 |
13.2 |
27.0 |
42.7 |
5 |
5.9 |
8.1 |
8.1 |
12.9 |
27.3 |
42.1 |
50 |
5.8 |
7.5 |
7.6 |
11.4 |
25.1 |
39.6 |
500 |
5.8 |
8.1 |
8.1 |
11.4 |
23.5 |
37.7 |
F2 litters |
||||||
0 |
5.8 |
8.1 |
8.3 |
13.9 |
27.0 |
40.5 |
5 |
5.8 |
8.5 |
8.5 |
14.4 |
26.9 |
42.0 |
50 |
6.0 |
8.1 |
8.1 |
13.4 |
25.3 |
39.5 |
500 |
5.8 |
8.1 |
8.1 |
12.1 |
22.3 |
34.6 |
Effect on fertility: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 50 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
There is no reproductive toxicity study with the target substance available. Data generated with LAB and LABS Na was considered pivotal to this endpoint.
LAB: Groups of 30 female and 30 male rats were exposed to concentrations of 0, 5, 50 and 500 mg/kg/day of test substance by oral gavage beginning ten weeks before mating. Animals were then mated. The resulting generation was also exposed to the test substance and mated. Exposure continued through the mating period, and in females through the gestation and lactational periods. All animals were sacrificed and necropsied after exposure. Pups not used for mating were sacrificed at weaning. During the study, animals were observed for clinical signs, mortality, and body weight. Pups were examined for viability and body weight gain. Reproductive indices were also calculated. The NOAEL for parental toxicity was 50 mg/kg/day and the LOAEL was 500 mg/kg/day on reduced weight gain and litter size in the high dose group. The NOAEL for offspring was 50 mg/kg/day based on reduced body weight gain and survival in the high and mid-dose groups. The LOAEL for offspring was 500 mg/kg/day.
LABS Na: was fed for 84 days to 4 groups of weanling rats for two years (three generations). 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 (0.5%).
The target substance is considered not to be toxic to reproduction.
Effects on developmental toxicity
Description of key information
There is no reproductive toxicity study with the target substance available. Data generated with the category substances LAB and LABS Na were considered pivotal to this endpoint. The target substance is considered to have an NOAEL of 125 mg/kg/day for maternal toxicity and embryotoxicity.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP study published in peer-reviewed journal.
- Justification for type of information:
- Category Approach; test material is reference substance LAB. The justification for the read across category approach is included in IU section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- Groups of 24 mated female rats were exposed to concentrations of 0, 125, 500, and 2000 mg/kg bw/d of test substance by oral gavage during days 6-15 of gestation. On day 20 of gestation, the animals were sacrificed and the uterine contents examined. Pups were removed by caesarean section and soft tissue and skeletal examinations performed.
- GLP compliance:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: 7 nights, if female was still not pregnant, she was moved to another male for an additional 7 nights, and then to a third male if needed
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): individually - Duration of treatment / exposure:
- days 6-15 of gestation
- Frequency of treatment:
- daily
- Duration of test:
- section on 20th of gestation
- No. of animals per sex per dose:
- 24 mated females rats/dose and control groups
- Control animals:
- yes, concurrent vehicle
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 6, 10, 12, 15, and 20 of gestation
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: complete post-mortem examination - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: number of live and dead fetuses, sex of fetuses - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter - Statistics:
- Nair, RS, Auletta, CS, Schroeder, RE, and Johannsen, FR (1990). Chronic toxicity, oncogenic potential, and reproductive toxicity of p-nitroaniline in rats. Fundam. Appl. Toxicol. 15, 607-621.
- Indices:
- incidence of fetuses and litters with malformations and resorption sites
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Mean body weight gains were significantly decreased since the 10th day of gestation in the 2000 mg/kg bw/d group (p <= 0.01) and from the 12th to 15th day of gestation in the 500 mg/kg bw/d group; compensatory increases of weight gains occurred in the posttreatment period in these groups; food consumption was significantly reduced during treatment (p <= 0.01) and significantly increased after treatment in the 500 mg/kg bw/d (p <= 0.005) and 2000 mg/kg bw/d groups (p 0= 0.01). - Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 500 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 500 mg/kg bw/day
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
No treatment related increases in soft tissue malformations and variations were found; the incidence of fetuses with at least one ossification variation was significantly increased in the 2000 mg/kg/ bw/d group (p0.05): main variations were incomplete ossification of several cranial bones and vertebral elements and in addition in the 500 mg/kg bw/d group the incidence of rudimentary rib structures; a significant decrease of those variations in the 125 mg/kg bw/d group was not considered treatment related (p <= 0.05). - Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- There is no developmental toxicity study available with the target substance. Data generated with the category substances LAB and LABS Na are considered pivotal to this endpoint. LAB was not classified as a teratogen; therefore the target substance is not classified as teratogen.
- Executive summary:
This study examined the potential developmental toxicity of the test substance. Groups of 24 mated female rats were exposed to concentrations of 0, 125, 500, and 2000 mg/kg bw/d of test substance by oral gavage during days 6-15 of gestation. On day 20 of gestation, the animals were sacrificed and the uterine contents examined. Pups were removed by caesarean section and soft tissue and skeletal examinations performed. The LOAEL for maternal toxicity was 500 mg/kg bw/day based on reduced body weight gain. The NOAEL for maternal toxicity was 125 mg/kg bw/day. The LOAEL for embryotoxicity was also 500 mg/kg bw/day based on increased incidence of incomplete ossification. The NOAEL for embryotoxicity was also 125 mg/kg bw/day. Since no embryotoxicity was seen at doses that were not toxic to the maternal animals, the test substance is not classified as teratogenic.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well documented peer-reviewed journal article by researchers at GLP contract testing laboratory.
- Justification for type of information:
- Category Approach; test material is reference substance LABS Na Salt. The justification for the read across category approach is included in IU section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- 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:
- yes
- Remarks:
- not stated, but likely GLP
- Limit test:
- no
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- Mice were held in plastic containers at standard environmental conditions (20 =/- 1 degrees C, 50 =/- 5% relative humidity) and free access to drinking water and food (Spratt's Laboratory Diet No. 1).
- 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
- No. of animals per sex per dose:
- 20 female mice per dose
- 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/day) because the likely maximum human intake of detergent from ordinary kitchen use has been estimated at 0.14 mg/kg/day, thus providing factors of 1-2 times the human exposure level. Two further doses were also investigated (300 and 600 mg/kg/day) based on previous toxicity data suggesting that these would impair maternal economy and result in obvious adverse effects.
- Maternal examinations:
- All animals were observed daily for signs of adverse reactions and were weighed regularly throughout gestation. All animals that died, and survivors at termination, were dissected and examined for macroscopic changes.
- Ovaries and uterine content:
- Ovaries were examined and the number of corpora lutea counted.
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Among parent animals treatment at 300 and 600 mg/kg bw d was associated with increased mortality (35% and 90% respectively). At 300 mg/kg bw d weight gain was retarded only during the first four days. No assessment could be made at 600 mg/kg bw d, due to the high mortality rate. Necropsy revealed a ubiquitous occurrence of tympanites, sometimes associated with gastritis. Pregnancy rate was essentially comparable for all groups. - Dose descriptor:
- NOAEL
- Effect level:
- 2 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
At doses with no maternal toxicity, 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 doses with maternal toxicity there was an increased foetal loss and reduced litter size due almost entirely to total litter loss, which was considered to be a secondary effect due to the maternal toxicity. The incidences of major malformations was not affected; minor skeletal or visceral anomalies were increased at 300 mg/kg. - Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Maternal NOAEL = 2 mg/kg bw/day; Teratogenicity NOAEL = 300 mg/kg bw/day
- Executive summary:
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.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Original study report not available for review.
- Justification for type of information:
- Category Approach; test material is reference substance LABS Na Salt. The justification for the read across category approach is included in IU section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Principles of method if other than guideline:
- 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.
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Charles River CD strain
- Route of administration:
- other: oral in distilled 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
- Control animals:
- yes, concurrent no treatment
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
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. The pregnancy rate was comparable at all dosages. - Dose descriptor:
- NOAEL
- Effect level:
- 300 other: mg/kg
- Basis for effect level:
- other: maternal toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
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. - Dose descriptor:
- NOAEL
- Effect level:
- 300 other: mg/L
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- NOAEL = 300 mg/kg for both maternal and teratogenicity
- Executive summary:
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.
Referenceopen allclose all
Incidence of Fetal Skeletal Alterations
Dose (mg/kg/day) |
0 |
125 |
500 |
2000 |
Rudimentary ribs |
20 (14) |
15 (10) |
48 (18) |
52 (20) |
Total fetuses (litters) with variations |
82 (21) |
54 (22) |
82 (23) |
106 (22) |
% fetuses (litters) with variations |
57.3 (91.3) |
41.9 (95.7) |
57.2 (100) |
79.7 (100) |
The maternal NOAEL of 2 mg/kg bw d is considered very conservative because the range (2-300 mg/kg bw d) was too wide, especially considering the repeated dose toxicity studies (section 7.5.1) which give much higher NOAEL values.
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.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 125 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
There was no developmental toxicity study available with the target substance. Data generated with the target substances LAB and LABS Na is considered pivotal to this endpoint.
Groups of 24 mated female rats were exposed to concentrations of 0, 125, 500 and 2000 mg/kg bw/day of LAB by oral gavage during days 6 -15 of gestation (OECD guideline 414). On day 20 of gestation, the animals were sacrificed and the uterine contents examined. Pups were removed by caesarean section and soft tissue and skeletal examinations performed. The LOAEL for maternal toxicity was 500 mg/kg bw/day based on reduced body weight gain. The NOAEL for maternal toxicity was 125 mg/kg bw/day. The LOAEL for embryotoxicity was also 500 mg/kg bw/day based on increased incidence of incomplete ossification. The NOAEL for embryotoxicity was also 125 mg/kg bw/day. Since no embryotoxicity was seen at doses that were not toxic to the maternal animals, the test substance is not classified as teratogenic.
As described above, the reproductive toxicity potential of LAB was also tested in an OECD guideline 416 study. The NOAEL for parental toxicity was 50 mg/kg/day and the LOAEL was 500 mg/kg/day on reduced weight gain and litter size in the high dose group. The NOAEL for offspring was 50 mg/kg/day based on reduced body weight gain and survival in the high and mid-dose groups. The LOAEL for offspring was 50 mg/kg/day.
Pregnant female mice were exposed to LABS Na 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.
In a second developmental toxicity study, female rats were given LABS Na 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. NOAEL was 300 mg/kg for both maternal and teratogenicity.
Justification for classification or non-classification
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.

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