Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

Fertility studies and developmental toxicity studies were conducted with the read-across source substance C10-14 LAS as well as with the target substance C10-13 LAS. Overall, results from these studies indicate no adverse effect on the fertility of the parenteral animals and development of the offspring. The read-across target substance C10-14 LAS has very similar composition to the sponsored substance C10-13 LAS (slight differences in C10 and C14 content).

The target and source substances present a similar potency of toxicological behaviour with respect to acute oral toxicity, with LD50 being 1080 mg/kg bw for the target substance and 900 mg/kg bw for the source substance. With respect to repeated dose endpoint, for the studies available on the source and target substances, the doses at which effects were observed were similar (after consideration of exposure route and dose spacing) as were the observed effects. 

The reproductive toxicity study of the source substance (C10-14 LAS) in rats across three generations was conducted according to the accepted scientific principles (Buehler et al., 1971). Rats were divided into 4 groups and administered 0 (control), 0.02, 0.1 and 0.5% (corresponding to 14, 70 and 350 mg/kg bw/day, respectively) test substance added to their diets. Administration of the test substance to male and female rats by diet for three generations resulted in a NOAEL of 350 mg/kg bw/day for P0, F1, F2 and F3 generations, based on absence of marked effects on general reproduction parameters, growth, body weight, organ weight, body weight to organ weight ratio, haematology and histopathology parameters at the highest dose. This reproductive toxicity study is acceptable and satisfies accepted scientific principles.

Link to relevant study records
Reference
Endpoint:
three-generation reproductive toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read-across from a study predating current guidelines and GLP, but adequate for assessment.
Justification for type of information:
The reproductive toxicity study of C10-13 LAS is based on read-across with C10-14 LAS. The read-across justification is presented in the assessment reports section. A cross-reference is made to that record.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Remarks:
read-across justification
Key result
Dose descriptor:
NOAEL
Remarks:
Systemic toxicity
Effect level:
350 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: No effects observed at the highest dose of 350 mg/kg bw/day (0.5% LAS in diet)
Key result
Dose descriptor:
NOAEL
Remarks:
Reproductive toxicity
Effect level:
350 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: No effects observed at the highest dose of 350 mg/kg bw/day (0.5% LAS in diet)
Key result
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Remarks:
Systemic toxicity
Effect level:
350 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: No effects observed at the highest dose of 350 mg/kg bw/day (0.5% LAS in diet)
Key result
Dose descriptor:
NOAEL
Remarks:
Reproductive toxicity
Effect level:
350 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: No effects observed at the highest dose of 350 mg/kg bw/day (0.5% LAS in diet)
Key result
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Generation:
F1b
Effect level:
350 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: No effects observed at the highest dose of 350 mg/kg bw/day (0.5% LAS in diet)
Key result
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Generation:
F2b
Effect level:
350 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: No effects observed at the highest dose of 350 mg/kg bw/day (0.5% LAS in diet)
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
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
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity 

Study 1 (C10-14 LAS-Na): 

A three-generation reproductive toxicity study was conducted with the read-across substance C10-14 LAS, sodium salt in Charles River rats. The test substance was administered to groups of 50 males and 50 females in the feed at doses of 0, 0.02, 0.1, and 0.5% (0, 14, 70, and 350 mg/kg bw/day) for 84 days and evaluated for three generations (a total of 2 years). 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-generations) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were re-mated 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. All rats sacrificed at weaning were normal with respect to growth, organ to body weight ratios, gross pathology, and histopathology, and did not vary from controls. There were a number of statistically significant hematologic values, though these differences were small and did not indicate a trend or pattern. Overall, no significant effects were observed up to the highest dose tested. Based on the results, the systemic, reproductive and developmental toxicity NOAEL of 350 mg/kg bw/day for P0, F1, F2 and F3 generations based on the absence of treatment-related effects on general reproduction parameters, growth, body weight, organ weight, body weight to organ weight ratio, haematology and histopathology up to the highest dose (Buehler, 1971).

Effects on developmental toxicity

Description of key information

Furthermore, four reliable prenatal developmental toxicity studies in rat, mouse and rabbit are available to evaluate the potential developmental effects of LAS(Palmer et al., 1971; 1975 a, b, c) These studies performed with the target substance (C10-13 LAS) support the conclusion of no adverse effects of C10-13 LAS on reproductive health.The derived NOAELs for developmental effects (2 mg/kg bw in mice and rabbits studies or 300 mg/kg bw/d in rats) were either the same or higher than the NOAELs for maternal toxicity.The observed fetal toxicity was due to maternal toxicity at high dose levels. Because of the very wide range between the 2 mg/kg bw/day and 300 mg/kg bw/day doses in both the mice and rabbit study, and high maternal toxicity at 300 mg/kg bw/d, the maternal and developmental NOAEL of 2 mg/kg bw/day were considered very conservative. Therefore, based on the entire data set, the maternal and developmental NOAELs were determined to be 300 mg/kg bw/day from the study on rats, WoE study 1.

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental toxicity
Type of information:
experimental study
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
Qualifier:
no guideline followed
Principles of method if other than guideline:
The purpose of this study was to evaluate the teratogenic potential of linear alkylbenzene sulphonate (LAS) in rats. Twenty female rats/dose were divided into 5 groups and administered 0 (water), 0.2, 2.0, 300 and 600 mg/kg bw/day of test substance by oral gavage from day 6 to 15 of gestation. Throughout experiment animals were observed daily for signs of malreaction and weighed regularly. After euthanasia on day 20, their uterine content was examined for number of implantations, viable young and embryonic deaths along with ovaries, number of corpora lutea and viable pups. Body weight, incidents of external malformation, visceral and skeletal anomalies were also recorded in pups. Non parametric methods were used for statistical analysis and on the basis of adverse effects, NOAEL value was derived for maternal toxicity and teratogenicity.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
other: CD rats
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Mass., U.S.A. and St-Aubin-les-Elbeuf, France.
- Housing: Female rats (5 per cage) were housed in opaque plastic cages.
- Diet: Spratt’s Laboratory Diet No. 1, ad libitum.
- Drinking water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 1°C
- Humidity: 50 ± 5 % RH
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
- Preparation of dosing solutions: Doses were prepared on daily basis as series of graded aqueous solutions for oral dosing.
- Administration of dosage: Standard volume of doses was administered orally by gastric intubation. Control animals were dosed with water.
- Duration of dosage: Doses were commenced on day 6 after detection of vaginal plug in rats and continued daily up to and including day 15 of gestation.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Mating was confirmed by the detection of vaginal plug in rats.
Duration of treatment / exposure:
Animals were dosed for 10 days [from Day 6 (after detection of vaginal plug) to Day 15].
Frequency of treatment:
daily from day 6 after detection of the vaginal plug to till day 15
Duration of test:
21 days
Dose / conc.:
0 mg/kg bw/day
Remarks:
(control)
Dose / conc.:
0.2 mg/kg bw/day
Dose / conc.:
2 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
600 mg/kg bw/day
No. of animals per sex per dose:
20 female rats per dose
Control animals:
yes
Details on study design:
- Dose selection rationale: Two doses formed 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 (300 and 600 mg/kg bw/day) were also investigated 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 malreaction 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:
After euthanasia, uteri were dissected and examined to determine the number of:
a) Implants
b) Viable young
c) Embryonic deaths (abortion/resorption sites)

Ovaries were examined and number of corpora lutea were also recorded.
Fetal examinations:
After weighing, fetus were examined for external malformations, visceral anomalies by free and sectioning and skeletal examination was performed by alizarin staining.
Statistics:
Differences in mean values were statistically analyzed by non-parametric method i.e. Wilcoxon test.
Indices:
Mating index: (number of confirmed mating/ number of animals cohabitated) X 100
Historical control data:
In CD rats, percentage of major malformations, minor visceral anomalies and minor skeletal anomalies were recorded as 0.41%, 2.02% and 2.35%, respectively in 51349 examined fetuses.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Toxic effects were generally associated with the gastrointestinal tract disturbances.
Dermal irritation (if dermal study):
not examined
Mortality:
mortality observed, treatment-related
Description (incidence):
Single mortality was observed at 600 mg/kg bw/day.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Retarded weight gain was observed on 600 mg/kg bw/day.
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 examined
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
Pre-implantation embryonic losses were 18.1%, 23.2%, 36.9%, 15.6% and 20.3% at 0, 0.2, 2, 300 and 600 mg/kg bw/day, respectively.
Post-implantation embryonic losses were 2.8%, 12.4%, 5.9%, 3.6% and 3.1% at 0, 0.2, 2, 300 and 600 mg/kg bw/day, respectively.
Total litter losses by resorption:
not specified
Description (incidence and severity):
Only single litter was lost at 0.2 mg/kg bw/day but not significant as no dose response relationship was followed.
Early or late resorptions:
not specified
Dead fetuses:
no effects observed
Description (incidence and severity):
Embryonic deaths were 0.3, 0.7, 0.6, 0.4 and 0.4 at 0, 0.2, 2, 300 and 600 mg/kg bw/day, respectively.
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Description (incidence and severity):
Mating index was also comparable across all doses when compared to the control group.
Other effects:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: mortality and retarded weight gain at 600 mg/kg bw/day
Abnormalities:
not examined
Fetal body weight changes:
no effects observed
Description (incidence and severity):
Although the fetal weights differed significantly at 0.2 and 2 mg/kg bw/day, these changes does not represent an adverse change because there was no consistent dose relationship and were invariably due to higher mean pub weight in the test group.
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No test substance related effect or statistically significant differences were observed.
Changes in sex ratio:
not specified
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
Litter size and weights were comparable across all doses when compared to the control group.
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
No test substance related or statistically differences in the incidence of major malformations observed even a maternally toxic dosage.
Skeletal malformations:
no effects observed
Description (incidence and severity):
Incidences of skeletal abnormalities were comparable across all doses when compared to the control group.
Visceral malformations:
no effects observed
Description (incidence and severity):
Minor visceral anomalies were increased at 600 mg/kg bw/day (not significant statistically) but same incident was also observed in control group.
Other effects:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: marginal retardation of sternebral ossification at the highest dose
Key result
Abnormalities:
effects observed, treatment-related
Localisation:
skeletal: sternum
Description (incidence and severity):
Marginal retardation of sternebral ossification at the highest dose level
Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
600 mg/kg bw/day (nominal)
Treatment related:
not specified
Relation to maternal toxicity:
developmental effects as a secondary non-specific consequence of maternal toxicity effects

Table 1: Mating index of the maternal animals (Palmer et.al., 1975)

Dose 

Number of confirmed mating

Number of animals cohabitated

 		 Mating index %  
0 15 20 75
0.2 15 20 75
2 18 20 90
300 16 20 80
600 16 19 84

Table 2: Summary of adult performance (Palmer et.al., 1975)

Observations  Number of animals at dosage (mg/kg bw/day)
0 0.2 2 300 600
Mated  20 20 20 20 20
Died  0 0 0 0 1
Non-pregnant 5 5 2 4 3
Total litter loss 0 1 0 0 0
With viable young  15 14 18 16 16
Body weight change  - - - - retarded gain 

Table 3: Group mean litter data (Palmer et.al., 1975)

Dosage (mg/kg bw/day)

 Number of litters  Litter size viable young  Embryogenic deaths  Implantations  Corpora lutea  Embryonic loss %  Litter weight (g) Fetal weight (g)
Pre-implantation  Post-implantation 
0 15 (A & B) 9.9 0.3 10.3 12.5 18.1 2.8 36.15 3.66
0.2 15 (A) 9.1 0.7 9.8 12.7 23.2 12.4 - -
14 (B) 9.8 0.6 10.4 12.8 18.4 6.1 37.14 3.84a
2 18 (A & B) 8.2 0.6 8.8 13.9 36.9 5.9 31.62 3.94b
300 16 (A & B) 9.6 0.4 10 12.4 15.6 3.6 35.72 3.78
600 16 (A & B) 10.4 0.4 10.8 13.9 20.3 3.1 37.49 3.63

A: Mean value includes all surviving animals showing evidence of implantation, including those with total litter loss

B: Mean value includes only animals bearing viable young at termination

Difference from controls statistically significant at Wilcoxon test: aP < 0.05 and bP < 0.001.

Table 4:

a)       Group mean incidence for major and minor malformations (Palmer et.al., 1975)

Dosage (mg/kg bw/day) Number of young
Major malformations  Minor malformations*
Gross or visceral Skeletal
Examined  Affected  Examined  Affected  Examined  Affected 
Total number  Mean (%)  Total number  Mean (%)  Total number  Mean (%) 
0 149 0 0 33 1 2.2 116 2 2
0.2 137 0 0 26 0 0 111 2 1.7
2 147 0 0 22 0 0 125 5 5.5
300 153 1 0.6 30 0 0 122 4 3.6
600 166 0 0 34 1 6.7 132 2 1.8

b) Group mean incidence for pups with extra ribs (Palmer et.al., 1975)

Dosage (mg/kg bw/day) Mean percent incidences of pups with extra lumber ribs*
0 18.6
0.2 33.1
2 21.3
300 12.9
600 15.3

* Young showing major malformations excluded

Conclusions:
Based on the results, the maternal toxicity and developmental toxicity NOAELs were determined to be 300 mg/kg bw/day based on retarded weight gain and mortality in treated females at higher dose and based on absence of major, minor and skeletal malformations at highest dose respectively.
Executive summary:

A pre-natal developmental toxicity study is conducted with C10-13 LAS, sodium salt in pregnant female CD rats. The test substance was administered to groups of 20 pregnant female rats via oral gavage at doses of 0, 0.2, 2, 300 and 600 mg/kg bw/day from gestation day 6 (GD 6) till GD 15. All animals were observed daily for clinical signs of toxicity and were weighed regularly throughout the gestation. On GD 17, animals were euthanised and uteri were examined for number of implantations, viable youngs and embryonic deaths (abortion or resorption sites). Ovaries were examined and number of corpora lutea were also recorded. Individual foetus was weighed and examined for external malformations. About one third of the foetuses were examined for visceral anomalies and remaining two thirds for skeletal anomalies. Moderate maternal toxicity was observed at the highest dose due to retarded weight gain and mortality. These effects were associated with the gastrointestinal disturbances. No instances of major, minor and skeletal malformations were observed up to the highest dose of 600 mg/kg bw/day with the exception of a marginal retardation of sternebral ossification at 600 mg/kg. Based on the results, the maternal toxicity and developmental toxicity NOAELs were determined to be 300 mg/kg bw/day based on retarded weight gain and mortality in treated females at higher dose and based on absence of major, minor and skeletal malformations at highest dose respectively (Palmer, 1975a).  

Endpoint:
developmental toxicity
Type of information:
experimental study
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
Qualifier:
no guideline followed
Principles of method if other than guideline:
The aim of this study was to evaluate the teratogenic potential of linear alkylbenzene sulphonate (LAS) in mice. Twenty female mice/dose were assigned into 5 groups and administered 0 (water), 0.2, 2.0, 300 and 600 mg/kg bw/day of test substance by oral gavage from day 6 to 15 of gestation. Throughout the experiment animals were observed daily for signs of malreaction and weighed regularly. After euthanasia on day 17, their uterine content was examined for number of implantations, viable young and embryonic deaths. Body weight, incidents of external malformation, visceral and skeletal anomalies were also recorded in pups. Non parametric methods were used for statistical analysis and on the basis of adverse effects, NOAEL value was derived for maternal toxicity and teratogenicity.
GLP compliance:
not specified
Limit test:
no
Species:
mouse
Strain:
CD-1
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Mass., U.S.A. and St-Aubin-les-Elbeuf, France.
- Housing: Femlale mice (5 per cage) were housed in opaque plastic cages.
- Diet: Spratt’s Laboratory Diet No. 1, ad libitum.
- Drinking water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 1°C
- Humidity: 50 ± 5 % RH
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
- Preparation of dosing solutions: Doses were prepared on daily basis as series of graded aqueous solutions for oral dosing.
- Administration of dosage: Standard volume of doses was administered orally by gastric intubation. Control animals were dosed with water.
- Duration of dosage: Doses were commenced on day 6 after detection of vaginal plug in mice and continued daily up to and including day 15 of gestation.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Mating was confirmed by the detection of vaginal plug in mice.
Duration of treatment / exposure:
Animals were dosed for 10 days [from Day 6 (after detection of vaginal plug) to Day 15].
Frequency of treatment:
daily from day 6 after detection of the vaginal plug to till day 15
Duration of test:
18 days
Dose / conc.:
0 mg/kg bw/day
Remarks:
(control)
Dose / conc.:
0.2 mg/kg bw/day
Dose / conc.:
2 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
600 mg/kg bw/day
No. of animals per sex per dose:
20 female mice per dose
Control animals:
yes
Details on study design:
- Dose selection rationale: Two doses formed 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/day, thus providing factors of 1-2 times the human exposure level. Two further doses (300 and 600 mg/kg bw/day) were also investigated 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 malreaction 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:
After euthanasia, uteri were dissected and examined to determine the number of:
a) Implants
b) Viable young
c) Embryonic deaths (abortion/resorption sites)
Fetal examinations:
After weighing, fetus were examined for external malformations, visceral anomalies by free and sectioning and skeletal examination was performed by alizarin staining.
Statistics:
Differences in mean values were statistically analyzed by non-parametric method i.e. Wilcoxon test.
Indices:
Mating index: (number of confirmed mating/ number of animals cohabitated) X 100
Historical control data:
In CD-1 mice, percentage of major malformations, minor visceral anomalies and minor skeletal anomalies were recorded as 0.84%, 3.68% and 5.32%, respectively in 22389 examined fetuses.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity was observed at 300 and 600 mg/kg bw/day. Toxic effects were generally associated with the gastrointestinal tract disturbances.
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
There was 90 and 35% mortality in 600 and 300 mg/kg bw/day dose groups, respectively while no mortality was observed in 0.2 and 2 mg/kg bw/day.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight gain was retarded in the animals of 300 mg/kg bw/day and weight loss was observed at 600 mg/kg bw/day but due to high mortality rate at this dose, no conclusion can be drawn.
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 examined
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity was observed in mice at 300 and 600 mg/kg bw/day.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Number of abortions:
effects observed, treatment-related
Description (incidence and severity):
At 300 and 600 mg/kg bw/day, 4 and 1 litters were lost, respectively.
Pre- and post-implantation loss:
effects observed, treatment-related
Description (incidence and severity):
Post-implantation embryonic losses were 6.5%, 11.5%, 9.4%, 38.0% and 100% at 0, 0.2, 2, 300 and 600 mg/kg bw/day, respectively. No information on pre-implantation loss was provided in the research article.
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
effects observed, treatment-related
Description (incidence and severity):
Embryonic deaths were 0.8, 1.2, 1.2, 4.5 and 12.0 at 0, 0.2, 2, 300 and 600 mg/kg bw/day, respectively.
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Description (incidence and severity):
A marked decrease in mating index was observed at 600 mg/kg bw/day.
Other effects:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
2 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: marked maternal toxicity at 300 and 600 mg/kg bw/day
Abnormalities:
not examined
Fetal body weight changes:
no effects observed
Reduction in number of live offspring:
effects observed, treatment-related
Description (incidence and severity):
Increased fetal loss was observed at maternally toxic doses (i.e. 300 and 600 mg/kg bw/day) due to total litter loses.

Changes in sex ratio:
not specified
Changes in litter size and weights:
effects observed, treatment-related
Description (incidence and severity):
Reduced litter size was observed at maternally toxic doses (i.e. 300 and 600 mg/kg bw/day) due to total litter losses. This effect was a secondary consequence of maternal reaction as litter parameters were comparable with control values in mice. Litter weights were comparable across all doses when compared to the control group.Although the fetal weight differed significantly at 0.2 mg/kg bw/day when compared to control group, these changes does not represent an adverse change because there was no consistent dose relationship and were invariably due to higher mean pub weight in the test group.
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
No test substance related or statistically differences in the incidence of major malformations observed even at maternally toxic dosages.
Skeletal malformations:
effects observed, treatment-related
Description (incidence and severity):
An increase in incidences of skeletal abnormalities were observed at 300 mg/kg bw/day with respect to both concurrent controls as well as laboratory standard range (2.2 – 30.5%).
Visceral malformations:
effects observed, treatment-related
Description (incidence and severity):
Incidences of minor visceral anomalies were increased at 300 mg/kg bw/day (not significant statistically).
Other effects:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: higher incidence of skeletal and visceral anomalies at 600 mg/kg bw/day
Key result
Abnormalities:
effects observed, treatment-related
Localisation:
other: skeletal and visceral anomalies
Description (incidence and severity):
higher incidence of skeletal and visceral anomalies were observed at 600 mg/kg bw/day
Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
600 mg/kg bw/day
Treatment related:
yes
Relation to maternal toxicity:
not specified
Dose response relationship:
yes
Relevant for humans:
yes

Table 1: Mating index of the maternal animals (Palmer et.al., 1975)

Dose Number of confirmed mating Number of animals cohabitated Mating index %
0 17 20 85
0.2 18 20 90
2 18 20 90
300 13 13 100
600 1 2 50

Table 2: Summary of adult performance (Palmer et.al., 1975)

Observations Number of animals at dosage (mg/kg bw/day)
0 0.2 2 300M 600M
Mated 20 20 20 20 20
Died 0 0 0 7 18
Non-pregnant 3 2 2 0 1
Total litter loss 0 0 0 4 1
With viable young 17 18 18 9 0
Body weight change - - - retarded gain loss

M: Marked maternal toxicity

Table 3: Group mean litter data (Palmer et.al., 1975)

Dosage (mg/kg bw/day) Number of litters Litter size viable young Embryogenic deaths Implantations Embryonic loss % Litter weight (g) Fetal weight (g)
Post-implantation
0 17 (A & B) 11.7 0.8 12.5 6.5 11.34 0.97
0.2 18 (A & B) 10.4 1.2 11.6 11.5 10.98 1.05a
2 18 (A & B) 11.4 1.2 12.7 9.4 11.6 1.02
300 13 (A) 7.9 4.5 12.4 38 - -
9 (B) 11.3 1.3 12.7 10.5 10.83 0.95
600 1 (A) 0 12 12 100 - -

A: Mean value includes all surviving animals showing evidence of implantation, including those with total litter loss

B: Mean value includes only animals bearing viable young at termination

a: Difference from controls statistically significant at Wilcoxon test (P < 0.05)

Table 4:

a) Group mean incidence for major and minor malformations (Palmer et.al., 1975)

Dosage (mg/kg bw/day) Number of young
Major malformations Minor malformations*
Gross or visceral Skeletal
Examined Affected Examined Affected Examined Affected
Total number Mean (%) Total number Mean (%) Total number Mean (%)
0 198 0 0 49 1 2 149 18 11.7
0.2 187 2 1 42 3 9.8 143 14 10.2
2 206 0 0 59 2 3.5 147 19 13.3
300 102 1 0.8 26 3 12.2 75 26 33.7
600 0 - - - - - - - -

b) Group mean incidence for pups with extra ribs (Palmer et.al., 1975)

Dosage (mg/kg/day) Mean percent incidence of pups with extra ribs*
Cervical Lumbar
0 32.4 19.1
0.2 41.3 13.3
2 17.3 21.2
300 40.8 6.7
600 - -

* Young showing major malformations excluded

Conclusions:
Administration of linear alkylbenzene sulphonate (LAS) to female CD-1 mice by oral gavage during days 6-15 of gestation at dose levels of 0, 0.2, 2, 300 and 600 mg/kg bw/day resulted in a NOAEL of 2 mg/kg bw/day for maternal toxicity (based on marked maternal toxicity at 300 and 600 mg/kg bw/day) in treated females as compare to controls. The NOAEL for teratogenicity was also established at 2 mg/kg bw/day (based on higher incidence of skeletal and visceral anomalies at 300 mg/kg bw/day).
Executive summary:

A pre-natal developmental toxicity study is conducted with C10-13LAS, sodium salt in pregnant female CD-1 mice. The test substance was administered to groups of 20 pregnant female mice via oral gavage at doses of 0, 0.2, 2, 300 and 600 mg/kg bw/day from gestation day 6 (GD 6) till GD 15. All animals were observed daily for clinical signs of toxicity and were weighed regularly throughout the gestation. On GD 17, animals were euthanised and uteri were examined for number of implantations, viable youngs and embryonic deaths (abortion or resorption sites). Ovaries were examined and number of corpora lutea were also recorded. Individual foetus was weighed and examined for external malformations. About one third of the foetuses were examined for visceral anomalies and remaining two thirds for skeletal anomalies. Marked maternal toxicity was observed in mice at 300 and 600 mg/kg bw/day. These effects were associated with the gastrointestinal disturbances. Total litter loss (abortion and / or total resorption) also occurred as secondary consequence of the primary effect on mother. Higher incidences of skeletal abnormalities were also detected in mice foetus at 300 mg/kg bw/day group. Because of the very wide range between the 2 mg/kg bw/day and 300 mg/kg bw/day doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative. 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 young, mean litter parameters, including litter size and foetal loss, and incidence of major malformations were not statistically different from controls. Minor anomalies, including gross or visceral and skeletal anomalies, were increased. At the 600 mg/kg bw/day, there were no live births. Based on these data, the developmental toxicity NOAEL was considered to be 300 mg/kg bw/day (Palmer, 1975b).

Endpoint:
developmental toxicity
Type of information:
experimental study
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
Qualifier:
no guideline followed
Principles of method if other than guideline:
The aim of this study was to evaluate the teratogenic potential of linear alkylbenzene sulphonate (LAS) in rabbits. Thirteen female rabbits/dose were divided into 5 groups and administered 0 (water), 0.2, 2.0, 300 and 600 mg/kg bw/day of test substance by oral gavage from day 6 to 18 of gestation. Throughout the experiment animals were observed daily for signs of malreaction and weighed regularly. After euthanasia on day 29, their uterine content was examined for number of implantations, viable young and embryonic deaths. Ovaries of the rabbits were also examined and number of corpora lutea were counted. Body weight, incidents of external malformation, visceral and skeletal anomalies were also recorded in pups. Non parametric methods were used for statistical analysis and on the basis of adverse effects, NOAEL value was derived for maternal toxicity and teratogenicity.
GLP compliance:
not specified
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: East Anglian Rabbitries, Colchester, England
- Housing: Rabbits were housed individually in the metal cages equipped with wire mesh floor.
- Diet: Rabbits SG-1 diet, ad libitum.
- Drinking water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 2°C
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
- Preparation of dosing solutions: Doses were prepared on daily basis as series of graded aqueous solutions for oral dosing.
- Administration of dosage: Standard volume of doses was administered orally by gastric intubation. Control animals were dosed with water.
- Duration of dosage: Doses were commenced on day 6 after observation of coitus in rabbits and continued daily up to and including day 18 of gestation.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Mating was confirmed by observation of coitus in rabbits.
Duration of treatment / exposure:
Animals were dosed for 13 days [from Day 6 (after observation of coitus) to Day 18].

Frequency of treatment:
daily from day 6 after observation of coitus to till day 18
Duration of test:
30 days
Dose / conc.:
0 mg/kg bw/day
Remarks:
(control)
Dose / conc.:
0.2 mg/kg bw/day
Dose / conc.:
2 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
600 mg/kg bw/day
No. of animals per sex per dose:
13 female rabbits per dose
Control animals:
yes
Details on study design:
- Dose selection rationale: Two doses formed 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/day, thus providing factors of 1-2 times the human exposure level. Two further doses (300 and 600 mg/kg bw/day) were also investigated 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 malreaction 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:
After euthanasia, uteri were dissected and examined to determine the number of:
a) Implants
b) Viable young
c) Embryonic deaths (abortion/resorption sites)

Ovaries were examined and number of corpora lutea were also recorded.
Fetal examinations:
After weighing, fetuses were examined for external malformations followed by their dissection and examined for internal organ abnormalities and gonadal inspection for sex determination. The carcasses were preserved in alcohol for subsequent clearing, alizarin staining and skeletal examination.
Statistics:
Differences in mean values were statistically analyzed by non-parametric method i.e. Wilcoxon test.
Indices:
Mating index: (number of confirmed mating/ number of animals cohabitated) X 100
Historical control data:
In rabbits, percentage of major malformations, minor visceral anomalies and minor skeletal anomalies were recorded as 0.74%, 2.53% and 8.60%, respectively in 36508 examined fetuses.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Marked maternal toxicity was observed at 300 and 600 mg/kg bw/day. Toxic effects were generally associated with the gastrointestinal tract disturbances and affected rabbits showed diarrhea, anorexia, weight loss and cachexia prior to death.
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
There was 100, 84.6% and 7.6% mortality observed at 600, 300 and 2 mg/kg bw/day, respectively while no mortality was observed at 0.2 mg/kg bw/day.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight loss was observed at 300 and 600 mg/kg bw/day.
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 examined
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Number of abortions:
effects observed, treatment-related
Description (incidence and severity):
At 0.2, 2 and 300 mg/kg bw/day, 1, 1 and 2 litters were lost, respectively.
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
Pre-implantation embryonic losses were 12.6%, 17.7%, 17.0%, and 12.5%at 0, 0.2, 2 and 300 mg/kg bw/day, respectively.
Post-implantation embryonic losses were 14.2%, 15.4%, 20.0% and 100% at 0, 0.2, 2 and 300 mg/kg bw/day, respectively.
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
effects observed, treatment-related
Description (incidence and severity):
Higher instance of embryonic death (8.5) was observed at 300 mg/kg bw/day. Embryonic deaths were 1.7, 1.0, 1.4, and 8.5 at 0, 0.2, 2 and 300 mg/kg bw/day, respectively.
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Description (incidence and severity):
No effect was observed on the mating index.
Other effects:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
2 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: marked maternal toxicity and mortality at 300 and 600 mg/kg bw/day
Abnormalities:
not examined
Fetal body weight changes:
no effects observed
Description (incidence and severity):
No test substance related / statistically significant differences were observed in treated groups as compared to control group.
Reduction in number of live offspring:
effects observed, treatment-related
Description (incidence and severity):
Increased fetal loss was observed at maternally toxic doses (i.e. 300 and 600 mg/kg bw/day) due to total litter losses and number of young pups available for examination and adequate assessment of results were insufficient at these doses.
Changes in sex ratio:
not specified
Changes in litter size and weights:
effects observed, treatment-related
Description (incidence and severity):
Reduced litter size was observed at maternally toxic doses (i.e. 300 and 600 mg/kg bw/day) due to total litter losses. Litter weights were comparable across all doses when compared to the control group.
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
At maternally toxic dosages, number of young pups available for examination / adequate assessment of results were insufficient. No test substance related / statistically significant differences in the incidence of major malformations and minor anomalies were observed at 0.2 and 2 mg/ kg bw/day groups on comparison to the control group.
Skeletal malformations:
no effects observed
Description (incidence and severity):
At maternally toxic dosages, number of young pups available for examination / adequate assessment of results were insufficient. No test substance related / statistically significant differences in the incidence of skeletal abnormalities were observed at 0.2 and 2 mg/ kg bw/day on comparison to the control group.
Visceral malformations:
no effects observed
Other effects:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
2 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: no test substance related differences in the incidence of skeletal abnormalities, major malformations and minor anomalies were observed at this dose. Increased fetal mortality was observed at the two higher doses due to maternal toxicity.
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no

Table 1: Mating index of the maternal animals (Palmer et.al., 1975)

Dose Number of confirmed mating Number of animals cohabitated Mating index %
0 10 11 90
0.2 13 13 100
2 12 12 100
300 2 2 100
600# - - -

 #: Mating index cannot be calculated as all animals died at this dose.

Table 2: Summary of adult performance (Palmer et.al., 1975)

Observations Number of animals at dosage (mg/kg bw/day)
0 0.2 2 300M 600M
Mated 13 13 13 13 13
Died 2a 0 1 11 13
Non-pregnant 1 0 0 0 0
Total litter loss 1b 1 1 2 0
With viable young 9 12 11 0 0
Body weight change - - - Loss loss

a: Includes one animal dying of intubation error

b: Excluded from subsequent calculations due to pus in thoracic cavity and uterus

M: Marked maternal toxicity

Table 3: Group mean litter data (Palmer et.al., 1975)

Dosage (mg/kg bw/day) Number of litters  Litter size viable young  Embryogenic deaths  Implantations  Corpora lutea  Embryonic loss %  Litter weight (g) Fetal weight (g)
Pre-implantation  Post-implantation 
0 9 (A & B) 8.3 1.7 10 11.3 12.6 14.2 321.7 39.3
0.2 13 (A) 7.8 1 8.8 10.6 17.7 15.4 - -
12 (B) 8.5 0.8 9.3 10.7 13.4 8.4 323.3 38.5
2 12 (A) 7.3 1.4 8.8 11 17 20 - -
11 (B) 8 1.3 9.3 10.5 11.9 12.8 314.8 40.1
300 2 (A) 0 8.5 8.5 10 12.5 100 - -
600 No survivors - - - - - - - -

A: Mean value includes all surviving animals showing evidence of implantation, including those with total litter loss

B: Mean value includes only animals bearing viable young at termination

Table 4:

a)  Group mean incidence for major and minor malformations (Palmer et.al., 1975)

Dosage (mg/kg bw/day) Number of young
Major malformations Minor malformations*
Gross or visceral Skeletal
Examined Affected Examined Affected Examined Affected
Total number Mean (%) Total number Mean (%) Total number Mean (%)
0 75 3 3 72 7 11 72 8 11.9
0.2 102 0 0 102 3 3.3 102 7 8
2 88 1 1.3 87 1 1 87 8 9.5
300 0 - - - - - - - -
600 0 - - - - - - - -

b)  Group mean incidence for pups with extra ribs (Palmer et.al., 1975)

Dosage (mg/kg/day) Mean percent incidence of pups with extra ribs*
Lumbar
0 61
0.2 56.1
2 72.8
300 -
600 -

* Young showing major malformations excluded

Conclusions:
Administration of linear alkylbenzene sulphonate (LAS) to female NZW rabbits by oral gavage during days 6-18 of gestation at dose levels of 0, 0.2, 2, 300 and 600 mg/kg bw/day resulted in a NOAEL of 2 mg/kg bw/day for maternal toxicity (based on marked maternal toxicity and mortality at higher dose levels of 300 and 600 mg/kg bw/day) in treated females as compared to controls. The NOAEL for teratogenicity was also established at 2 mg/kg bw/day (based on no test substance related / statistically significant differences in the incidence of skeletal abnormalities, major malformations and minor anomalies at this dose).
Executive summary:

A pre-natal developmental toxicity study is conducted with C10-13LAS, sodium salt in pregnant New Zealand White rabbits. The test substance was administered to groups of 13 pregnant female rabbits via oral gavage at doses of 0, 0.2, 2, 300 and 600 mg/kg bw/day from gestation day 6 (GD 6) till GD 18. All animals were observed daily for clinical signs of toxicity and were weighed regularly throughout the gestation. After euthanasia on day 29, their uterine content was examined for number of implantations, viable young and embryonic deaths. Ovaries of the rabbits were also examined and number of corpora lutea were counted. Body weight, incidents of external malformation, visceral and skeletal anomalies were also recorded in pups. Marked maternal toxicity was observed at 300 and 600 mg/kg bw/day which were primarily associated with the gastrointestinal disturbances and affected rabbits showed diarrhoea, anorexia, weight loss and cachexia prior to death. Maternal mortality rate was 100, 84.6% and 7.6% at 600, 300 and 2 mg/kg bw/day, respectively while no mortality was observed at 0.2 mg/kg bw/day. Higher instance of embryogenic death was (8.5) was observed at 300 mg/kg bw/day. No effect was observed on the mating index. Increased foetal loss was observed at maternally toxic doses (300 and 600 mg/kg bw/day) due to total litter losses and number of young pups available for examination and adequate assessment of growth anomalies or malformations were insufficient at these doses. No test substance related / statistically significant differences in the incidence of major malformations and minor anomalies were observed at 0.2 and 2 mg/ kg bw/day in comparison to the control group.

Based on the results, the maternal toxicity and developmental toxicity NOAELs were determined to be 2 mg/kg bw/day (Palmer, 1975c).  

Endpoint:
developmental toxicity
Type of information:
experimental study
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
Qualifier:
no guideline followed
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
Dose / conc.:
0.2 mg/kg bw/day
Dose / conc.:
2 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
600 mg/kg bw/day
No. of animals per sex per dose:
no data
Control animals:
yes, concurrent no treatment
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Treatment at 600 mg/kg was associated with a transient diarrhea following initiation of treatment.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Change in body weight 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.
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
The pregnancy rate was comparable at all dosages.
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Abnormalities:
not specified
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 litter size and weights:
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.
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
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.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
chronic
Species:
mouse
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

Developmental toxicity

Study 1 (C10-13 LAS):

A pre-natal developmental toxicity study is conducted with C10-13 LAS, sodium salt in pregnant female CD rats. The test substance was administered to groups of 20 pregnant female rats via oral gavage at doses of 0, 0.2, 2, 300 and 600 mg/kg bw/day from gestation day 6 (GD 6) till GD 15. All animals were observed daily for clinical signs of toxicity and were weighed regularly throughout the gestation. On GD 17, animals were euthanised and uteri were examined for number of implantations, viable youngs and embryonic deaths (abortion or resorption sites). Ovaries were examined and number of corpora lutea were also recorded. Individual foetus was weighed and examined for external malformations. About one third of the foetuses were examined for visceral anomalies and remaining two thirds for skeletal anomalies. Moderate maternal toxicity was observed at the highest dose due to retarded weight gain and mortality. These effects were associated with the gastrointestinal disturbances. No instances of major, minor and skeletal malformations were observed up to the highest dose of 600 mg/kg bw/day. Based on the results, the maternal toxicity and developmental toxicity NOAELs were determined to be 300 mg/kg bw/day (based on retarded weight gain and mortality in treated females at higher dose) and 600 mg/kg bw/day (based on absence of major, minor and skeletal malformations at highest dose) respectively (Palmer, 1975a).  

 

Study 2 (C10-13 LAS):

A pre-natal developmental toxicity study is conducted with C10-13 LAS, sodium salt in pregnant female CD-1 mice. The test substance was administered to groups of 20 pregnant female mice via oral gavage at doses of 0, 0.2, 2, 300 and 600 mg/kg bw/day from gestation day 6 (GD 6) till GD 15. All animals were observed daily for clinical signs of toxicity and were weighed regularly throughout the gestation. On GD 17, animals were euthanised and uteri were examined for number of implantations, viable youngs and embryonic deaths (abortion or resorption sites). Ovaries were examined and number of corpora lutea were also recorded. Individual foetus was weighed and examined for external malformations. About one third of the foetuses were examined for visceral anomalies and remaining two thirds for skeletal anomalies. Marked maternal toxicity was observed in mice at 300 and 600 mg/kg bw/day. These effects were associated with the gastrointestinal disturbances. Total litter loss (abortion and / or total resorption) also occurred as secondary consequence of the primary effect on mother. Higher incidences of skeletal abnormalities were also detected in mice foetus at 300 mg/kg bw/day group. Because of the very wide range between the 2 mg/kg bw/day and 300 mg/kg bw/day doses, the maternal NOAEL of 2 mg/kg bw/day must be considered very conservative. 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 young, mean litter parameters, including litter size and foetal loss, and incidence of major malformations were not statistically different from controls. Minor anomalies, including gross or visceral and skeletal anomalies, were increased. At the 600 mg/kg bw/day, there were no live births. Based on these data, the developmental toxicity NOAEL was considered to be 300 mg/kg bw/day (Palmer, 1975b).

Study 3 (C10 -13 LAS):

A pre-natal developmental toxicity study is conducted with C10-13 LAS, sodium salt in pregnant New Zealand White rabbits. The test substance was administered to groups of 13 pregnant female rabbits via oral gavage at doses of 0, 0.2, 2, 300 and 600 mg/kg bw/day from gestation day 6 (GD 6) till GD 18. All animals were observed daily for clinical signs of toxicity and were weighed regularly throughout the gestation. After euthanasia on day 29, their uterine content was examined for number of implantations, viable young and embryonic deaths. Ovaries of the rabbits were also examined and number of corpora lutea were counted. Body weight, incidents of external malformation, visceral and skeletal anomalies were also recorded in pups. Marked maternal toxicity was observed at 300 and 600 mg/kg bw/day which were primarily associated with the gastrointestinal disturbances and affected rabbits showed diarrhoea, anorexia, weight loss and cachexia prior to death. Maternal mortality rate was 100, 84.6% and 7.6% at 600, 300 and 2 mg/kg bw/day, respectively while no mortality was observed at 0.2 mg/kg bw/day. Higher instance of embryogenic death was (8.5) was observed at 300 mg/kg bw/day. No effect was observed on the mating index. Increased foetal loss was observed at maternally toxic doses (300 and 600 mg/kg bw/day) due to total litter losses and number of young pups available for examination and adequate assessment of growth anomalies or malformations were insufficient at these doses. No test substance related / statistically significant differences in the incidence of major malformations and minor anomalies were observed at 0.2 and 2 mg/ kg bw/day in comparison to the control group. Based on the results, the maternal toxicity and developmental toxicity NOAELs were determined to be 2 mg/kg bw/day (Palmer, 1975c).

Study 4 (C10 -13 LAS):

A pre-natal developmental toxicity study is conducted with C10-13 LAS, sodium salt in pregnant pregnant rats. Female rats were given LAS orally in distilled water from gestation days 6 to 15 during pregnancy. Doses were 0.2, 2.0, 300 and 600 mg/kg. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Based on these effects, the maternal LOAEL is 600 mg/kg bw/d and the maternal NOAEL is 300 mg/kg bw/d. Pregnancy rates were comparable at all doses. 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. 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 marginal effects the developmental LOAEL is considered to be 600 mg/kg bw/d and the developmental NOAEL is 300 mg/kg bw/d (Palmer and Lovell 1971).

Justification for classification or non-classification

Based on the reproductive toxicity study with C10 – 14 LAS and developmental toxicity studies with C10 -13 LAS in rats, mice and rabbits, no classification is warranted for this endpoint according to EU CLP (1272/2008/EC) criteria.

Additional information