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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

Referenceopen allclose all

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-H is based on read-across with C10-14 LAS-Na. 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
Endpoint:
three-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
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 linear alkylbenzene sulphonate sodium salt (LAS) having C10 - 14 chain length distribution for reproductive toxicity potential in rats. Rats were divided into 4 groups and administered 0 (control), 0.02, 0.1 and 0.5% LAS added to their diets. Each group consisted of 50 males and 50 females randomized according to their litter and weight. After administration of LAS for 84 days when the parent animals (P0) were 107 – 112 days old, 20 female rats from each group were mated with 20 male rats from the same group. All females were separated from males on completion of 17 days and placed in the opaque plastic litter boxes containing clean, dry saw dust and sufficient paper for nesting. Litters were examined for deformities and number of pups were counted. The first litters of F1a and F2a generation were sacrificed at 21 days of age and 10 days after sacrifice of litters, all females were remated with different males from same group to obtain the F1b generation. Twenty males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies and remaining weanling rats were examined and sacrificed. 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. Average body weight, feed consumption and feed efficiency were recorded on weekly basis for the first 8 weeks for F1a and F2b generations. Once the reproductive studies were completed, five male and five female rats from each parenteral groups (F1a and F2b) were selected for necropsy and body weight, organ to body weight ratios were recorded. Routine haematology and histology studies were also performed. Weanling animals from F3a generation were treated similarly.
GLP compliance:
no
Remarks:
(predates GLP)
Limit test:
no
Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals or test system and environmental conditions:
Details on test animals and environmental conditions
TEST ANIMALS
- Age at study initiation:
a) Parent animals (P0): 107 – 112 days
b) F1b and F2b generation: 80 – 85 days
- Parent animals body weight at study initiation: 59.4 - 59.9 g (males) and 57.0 - 57.3 g (females)
- Housing:
a) Females after mating were placed in opaque plastic boxes containing clean, dry sawdust and paper for nesting
b) Weanling rats: Individual wire bottom cages
- Diet: Purina rat chow; ad libitum
- Drinking water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 76 ± 3 °F
- Humidity: 50 ± 5 %
- Photoperiod (hrs dark / hrs light): 12/12 hrs
Route of administration:
oral: feed
Vehicle:
other: diet
Details on exposure:
VEHICLE
- Concentration in vehicle: LAS was added to their diets at levels of 0.02, 0.1 and 0.5%

Details on mating procedure
- Premating exposure period: 84 days (P0 animals) and 80 – 85 days (F1b and F2b animals)
- Length of cohabitation: 17 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 were 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 P0 animals in the study: 107-112 days old

Dose / conc.:
14 mg/kg bw/day
Remarks:
0.02% in diet
Dose / conc.:
70 mg/kg bw/day
Remarks:
0.1% in diet
Dose / conc.:
350 mg/kg bw/day
Remarks:
0.5% in diet
No. of animals per sex per dose:
50 males and 50 females per group
Control animals:
yes, concurrent no treatment
Details on study design:
Rats were divided into 4 groups and administered 0 (control), 0.02, 0.1 and 0.5% LAS added to their diets. Each group consisted of 50 males and 50 females randomized according to their litter and weight. After administration of LAS for 84 days when the parent animals (P0) were 107 – 112 days old, 20 female rats from each group were mated with 20 male rats from the same group. All females were separated from males on completion of seventeen days and placed in the opaque plastic litter boxes containing clean, dry saw dust and sufficient paper for nesting. Litters were examined for deformities and number of pups were counted. The first litters of F1a and F2a generation were sacrificed at 21 days of age and 10 days after sacrifice of litters, all females were remated with different males from same group to obtain the F1b generation. Twenty males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies and remaining weanling rats were examined and sacrificed. 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. Average body weight, feed consumption and feed efficiency were recorded on weekly basis for the first 8 weeks for F1a and F2b generations. Once the reproductive studies were completed, five male and five female rats from each parenteral groups (F1a and F2b) were selected for necropsy and body weight, organ to body weight ratios were recorded. Routine haematology and histology studies were also performed. Weanling animals from F3a generation were treated similarly.
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Gross examination of all animals along with routine haematology was performed after completion of reproductive study.

BODY WEIGHT: Body weight was recorded on weekly basis for first 8 weeks (F1b and F2b generation)

FOOD CONSUMPTION AND COMPOUND INTAKE: Feed consumption and feed efficiency were recorded on weekly basis for 12 weeks.
Oestrous cyclicity (parental animals):
Not examined
Sperm parameters (parental animals):
Not examined
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 haematology and histology
Postmortem examinations (offspring):
Necropsy, body weight, organ to body weight ratios, routine haematology and histology.
Reproductive indices:
Fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth
Offspring viability indices:
Body weight gain
Clinical signs:
not specified
Mortality:
no mortality observed
Description (incidence):
There was no significant difference between mortality in control and treated group of rats as overall survival in this study exceeded 56% with the highest occurring in 350 mg/kg bw/day dose group (0.5% LAS in diet) as compared to 53% in control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Body weight and organ to body weight ratios of selected animals from high level group and controls at 8, 15 and 24 months were within normal limits. A statistically significant decrease in liver weights was noted in male rats at the low and mid dose levels at the 8-month sacrifice. As the decreased liver weight was within normal range, was not seen at the highest dose level, nor was seen at the 15- and 24-month sacrifices, it was not considered biologically significant.
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
During routine haematological evaluations, statistically significant borderline values were scattered among various treatment groups and were not considered as treatment related.
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
There were no microscopic differences test and control animals as no test related response were observed in any of the tissues. Although higher incidences of incurrent degenerative diseases like chronic interstitial nephritis and adrenal telangiectasis and fibroadenomas were observed in final autopsy but these were not related to test material related exposure.
Histopathological findings: neoplastic:
no effects observed
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
General reproductive parameters like fertility, gestation, parturition, neonatal viability, lactation and post weanling growth were normal across all test groups and comparable to control.
Dose descriptor:
NOAEL
Remarks:
Systemic toxicity
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)
Dose descriptor:
NOAEL
Remarks:
Reproductive toxicity
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)
Critical effects observed:
no
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
In F1b female group receiving 70 mg/kg bw/day (0.1% LAS in diet) dose, red blood cell count was high but as it was within the normal range as determined by previous experiments conducted in the same laboratory.
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Description (incidence and severity):
General reproductive parameters like fertility, gestation, parturition, neonatal viability, lactation and post weanling growth were normal across all test groups and comparable to control.
Dose descriptor:
NOAEL
Remarks:
Systemic toxicity
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)
Dose descriptor:
NOAEL
Remarks:
Reproductive toxicity
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)
Critical effects observed:
no
Clinical signs:
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
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
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
NOAEL
Generation:
F1b
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)
Critical effects observed:
no
Clinical signs:
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
Red blood cell count was depressed in the F2b females from high dose test group as compared to control but was within the normal range as determined by previous experiments conducted in the same laboratory.
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Description (incidence and severity):
No gross abnormalities were observed in any treatment group.
Histopathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Pancreatic lesions consisting of acinar atrophy and tissue degeneration leading to the fibrous tissue replacement was observed in the F2b males and mild islet cell hyperplasia was also indicated. General lesions were also increased in the group receiving highest level of LAS. As similar lesions were also identified in the control males as well as control animals from the other studies, so these were not considered to be treatment related.
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
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)
Critical effects observed:
no
Reproductive effects observed:
no

F3b generation:

Rats sacrificed at weaning were normal w.r.t growth and organ to body weight ratios, gross pathology and histology and did not differs from control. Although statistically significant differences were observed were in hematological values between control and test groups, these differences were small and does not indicate a pattern as these animals were young leading to more individual variation as compared to mature animal.

NOAEL for F3b generation (based on absence of effects on growth and organ to body weight ratios, gross pathology and histology parameters at the highest tested dose): 350 mg/kg bw/day

Table 1: Average body weight gain and feed utilization (initial 12 weeks) for two year feeding study in rats (Buehler et. al., 1970)

Dietary level (%)

Dose (mg/kg bw/day)

Sex

Initial weight (g)

Final weight (g)

Weight gain (g)

Feed consumption (g)

Feed efficiency

0

0

M

59.5

491.1

431.6

2117.9

0.204

F

57.2

289.4

232.2

1579.9

0.147

0.02

14

M

59.4

485.1

425.7

2095

0.203

F

57

279

222

1545.7

0.144

0.1

70

M

59.9

492.8

432.9

2163.9

0.2

F

57.2

284.5

227.3

1568.5

0.145

0.5

350

M

59.8

480

420.2

2087.9

0.201

F

57.3

275.9

218.6

1520

0.144

Table 2: Growth and organ to body ratio's for two year feeding study in rats (Buehler et. al., 1970)

Time (Months)

Dietary level (%)

Dose (mg/kg bw/day)

Sex

Body weight (g)

Organ to body weight (expressed as % of total body weight)

Liver

Kidney

8

0

0

M

575

3.45

0.59

F

349

3.28

0.64

0.5

350

M

576

3.47

0.62

F

291

3.49

0.71

15

0

0

M

623

3.08

0.6

F

375

3.05

0.67

0.5

350

M

622

2.95

0.6

F

423

2.99

0.58

24

0

0

M

645

2.91

0.77

F

460

3.16

0.64

0.5

350

M

673

2.55

0.68

F

488

3.18

0.68

Table 3: Hematologic values for two year feeding study in rats (Buehler et. al., 1970)

Time (Months)

Dietary level (%)

Dose (mg/kg bw/day)

Sex

RBC count

Hemoglobin

Hematocrit

WBC count

Differential white cells

I

II

III

IV

V

8

0

0

M

6.81

15.5

48

7800

12

86

2

0

0

F

6.26

15

45

5700

9

89

1

0

1

0.5

350

M

5.81b

15.1

45

8900

11

85

1

0

3

F

5.7

14.6

42

4950

12

86

1

0

1

15

0

0

M

9.52

17.1

51

11100

10

84

5

0

1

F

6.88

16

44

6600

12

82

4

0

2

0.5

350

M

8.43

15.9

49

7600

13

83

3

0

1

F

7.74

14.7

45

6850

16

80

2

0

2

24

0

0

M

7.14

13.6

43

10500

23

72

4

0

1

F

6.65

13.2

43

10500

21

74

5

0

1

0.5

350

M

7.24

13.9

45

12600

35

59b

5

0

1

F

6.15

13.7

44

7900

25

68

6

0

1

b: Groups significantly different from control group

Differential white cells: Neutrophil / heterophil (I), Lymphocyte (II), Monocyte (III), Basophil (IV) and Eosinophil (V)

Table 4: Summary of mating for reproduction study in rats (Buehler et. al., 1970)                                                                                                                                                                 

Generation Dietary level (%) Dose (mg / kg bw/day) 0 day number in litter 5 days 21 days
No. in litter before culling  No. in litter after culling  Total weigh, origA Total weight after cullingA Number weaned  Body weights 
Male pups Female Pups MotherB
Number WeightA Number WeightA
F1a 0 0 12.3 12.1 7.81 129.2 87.7 7.4 3.6 201.3 4.1 205.3 319.5
0.5 350 12.7 12.5 7.6 123.4 81.6 7.5 3.8 197.6 3.7 178.3 324.8
F1b 0 0 12.4 11.5 7.6 120.2 82.4 6.4 3.5 197.9 2.9 157.8 363.1
0.5 350 13.7 12.9 8 128.4 83.9 7.6 3.5 183.5 3.7 185 355.9
F2a 0 0 12.2 11.7 7.9 145.5 102.4 7.7 3.4 158.9 4.4 189.2 316.2
0.5 350 12.7 12.1 7.9 141.7 96.4 7.6 4 183.1 3.6 154.2 323.2
F2b 0 0 11.8 11.6 7.5 141.4 94.9 7.5 3.7 209.5 3.8 208.4 350
0.5 350 12.2 11.8 7.8 130.1 89.3 7.6 4.2 201.4 3.4 166.5 352.4
F3a 0 0 12.6 12.3 8 136.7 91.9 7.9 4 216.8 3.9 202.6 328.7
0.5 350 11.4 11.2 7.8 127 90.7 7.8 4 202.7 3.8 186.2 316.8
F3b 0 0 12.9 12.3 7.9 151.2 102.6 8.2 3.8 213.3 4.3 233.5 356.1
0.5 350 12.1 11.7 7.7 150.1 100.6 7.7 4.3 240.1 3.4 181.4 337.6

                                   

A: Total group weight of pups (g)

B: Weight in grams

Table 5: Summary of hematology for two year reproduction study in rats (Buehler et. al., 1970)

Generation

Dietary level (%)

Dose (mg/kg bw/day)

Sex

RBC count

Hemoglobin

Hematocrit

WBC count

Differential white cells

I

II

III

IV

V

F1b

0

0

M

7.45

16.5

50

6800

14

80

3

0

3

F

6.03

16.9

49

5800

18

77

3

0

2

0.5

350

 

M

6.23

16.4

49

6800

16

80

2

0

2

F

5.88

16

47

6900

21

74

2

0

3

F2b

0

0

M

7.78

16.1

49

7900

13

79

6

0

2

F

7.27

16.2

48

5500

14

80

5

0

1

0.5

350

M

7.15

16

-

8400

10

85

4

0

1

F

6.15b

16.2

49

6400

11

83

5

0

1

b: Groups significantly different from control group

Differential white cells: Neutrophil / heterophil (I), Lymphocyte (II), Monocyte (III), Basophil (IV) and Eosinophil (V)

Conclusions:
Administration of linear alkylbenzene sulphonate sodium salt (Na-LAS) to male and female Charles river rats in their diet over 2 years across 3 generations at dose of 0, 14 (0.02%), 70 (0.1%) and 350 (0.5%) mg/kg bw/day resulted into NOAEL of 350 mg/kg bw/day for Po, 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, hematology and histopathology parameters at the highest dose).

Executive summary:

The reproductive toxicity study of linear alkylbenzene sulphonate sodium salt (Na-LAS) in rats across three generations was conducted according to the accepted scientific principles.

Weanling rats and females after mated were housed in the individual wire bottom cages and opaque plastic boxes containing clean, dry sawdust and paper for nesting, respectively and maintained under standard laboratory conditions (temperature: 76 ± 3 °F, humidity: 50 ± 5 %, 12-hour light/12-hour dark cycle/day). The animals were allowed free access to the drinking water and food. Male and female rats (Charles River strain) were used in this study. Experiment was initiated by randomizing rats into 4 groups of 50 males and 50 females each according to litter and weight and LAS was added into their diet at levels of 0 (control), 0.02, 0.1 and 0.5%. Dietary levels of 0.02, 0.1 and 0.5% corresponds to 14, 70 and 350 mg/kg bw/day, respectively. When parent animals (Po) were 107 – 112 days old and had received test diets for 84 days, groups of 20 female’s rats from each group were mated with 20 males from same group. After 17 days of initial exposure to males, females were transferred to the opaque plastic litter boxes with the clean and dry saw dust along with sufficient paper for nesting.

Litters were examined for deformities and number of pups were counted. On the fourth day, number of pups in each litter was limited to 8 for equalizing the stress of lactation among dams. The first litters of F1a generation were sacrificed at 21 days of age and after interval of 10 days, all females were remated with different males from the same group to obtain F1b generation. Twenty females and 20 males were selected from each group at weaning to continue their respective diets and used in further reproductive studies while and all remaining weanling rats were sacrificed and examined. These rats were housed in the individual wire bottom cages and fed the same diet. Reproduction studies on these rats were started at age of 80 - 85 days in a similar manner to obtain F2a and F2b generation and continued as such until F3b generation was weaned.

Average body weights, feed consumption and feed efficiency were recorded on weekly basis for first 8 weeks (F1b and F2b). After completion of the reproductive studies, 5 males and 5 female rats were selected from each parenteral group (F1b and F2b) for necropsy and body weight, organ to body weight ratio was recorded. Routine haematology and histology were also performed. Weanling animals from F3a generation were treated similarly. No significant effects were observed in the Po, F1b, F2b and F3b animals even at the highest dose i.e. 350 mg/kg bw/day (0.5% diet).

Based on above, administration of linear alkylbenzene sulfonate sodium salt to male and female rats by diet for three generation reproductive toxicity at dose of 0, 14 (0.02%), 70 (0.1%) and 350 (0.5%)  mg/kg bw/day resulted into NOAEL of 350 mg/kg bw/day for Po, 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.

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, and the study in rats was considered to be the key study.

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