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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
three-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Unavailable - original study report dated 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1971

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test: Three-generation reproductive toxicity study
- Short description of test conditions: Na-LAS (chain length distribution C10-14) was fed for 84 days to 4 groups of weanling rats (3 dose levels, plus control), each dose consisting of 50 animals each of both sexes (PO-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (Fla- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the Flb-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old, and were continued until the F3b generation was weaned.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
Benzenesulfonic acid, mono-C10-14-alkyl derivs., sodium salts
EC Number:
285-600-2
EC Name:
Benzenesulfonic acid, mono-C10-14-alkyl derivs., sodium salts
Cas Number:
85117-50-6
IUPAC Name:
sodium 4-dodecylbenzenesulfonate
Details on test material:
- Name of test material (as cited in study report): Sodium salt LAS (C10-14)
- Activity: 98.1% on an anhydrous basis (41.9% active)
- Impurities (identity and concentrations): unreacted alkylbenzene and Na2SO4

Test animals

Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: (P) weanling; (F1) 21 days
- Weight at study initiation: (P) Males: average 59.4-59.9 g; Females: average 57.0-57.3 g; (F1) Males: group weight 183.5-214.2 g; Females: group weight 157.8-193.2 g
- Housing: individual wire bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 76 +/- 3
- Humidity (%): 50 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12 hrs

:

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on mating procedure:
premating exposure period 84 days
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
2 years ( 3 generations)
Frequency of treatment:
continuous in feed
Details on study schedule:
- F1 parental animals not mated until 80-85 days old
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: 107-112 days old
Doses / concentrationsopen allclose all
Dose / conc.:
14 mg/kg bw/day (nominal)
Remarks:
corresponding to 0.02% dose level in diet
Dose / conc.:
70 mg/kg bw/day (nominal)
Remarks:
corresponding to 0.1% dose level in diet
Dose / conc.:
350 mg/kg bw/day (nominal)
Remarks:
corresponding to 0.5% dose level in diet
No. of animals per sex per dose:
50
Control animals:
yes, concurrent no treatment
Details on study design:
Na-LAS (chain length distribution C10-14) was fed for 84 days to 4 groups of weanling rats (3 dose levels, plus control), each dose consisting of 50 animals each of both sexes (P0-generation).  When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days.  The first litters of each generation (F1a- and F2a-generation) were sacrificed at 21 days of age.  Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation.  From the F1b-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies.  Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old, and were continued until the F3b generation was weaned.

Examinations

Parental animals: Observations and examinations:
DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

Litter observations:
Deformities and number of pups, average body weights, feed consumption, feed efficiency.
Postmortem examinations (parental animals):
Necropsy, body weight, organ to body weight ratios, routine hematology and histology.
Postmortem examinations (offspring):
Necropsy, body weight, organ to body weight ratios, routine hematology and histology.
Reproductive indices:
fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No effects to average food consumption were noted in the initial twelve weeks
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
350 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive performance

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
For futher details see "details on results (F1)" section below
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
not specified
Anogenital distance (AGD):
not examined
Nipple retention in male pups:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not examined

Details on results (F1)

Rats sacrificed at weaning were normal with respect to growth, organ to body weight ratios, gross pathology, and histology, 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.

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
350 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed in sacrfied rats at weaning

Target system / organ toxicity (F1)

Critical effects observed:
no

Results: F2 generation

Effect levels (F2)

Key result
Dose descriptor:
NOAEL
Generation:
F2
Effect level:
350 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed

Target system / organ toxicity (F2)

Critical effects observed:
no

Overall reproductive toxicity

Key result
Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
No significant effects on reproduction were observed at the highest concentration tested. Based on this results the NOAEL (fertility) was determined to be 350 mg/kg bw/day (corresponding to 0.5% test item in diet).
Executive summary:

In a three-generation reproduction study Na-LAS (chain length distribution C10-14) was administered to 50 Charles River rats/sex/dose indietat dose levels of 0, 0.02%, 0.1% or 0.5% in diet (equivalent to 0, 14, 70 or 350 mg/kg bw/day, respectively) for 84 days (P0-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (F1a- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the F1b-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old and were continued until the F3b generation was weaned.

 

No significant effects were observed at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was 350 mg/kg bw (corresponding to 0.5% test item in diet).Based on these observations the NOAEL (fertility) was derived at 350 mg/kg bw/d (highest dose tested under the conditions of this study).