Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with 2-propanamine

Toxicity to reproduction

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

Test material information

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 / concentrations

Doses / concentrations 1

Dose / conc.:

14 mg/kg bw/day (nominal)

Remarks:

corresponding to 0.02% dose level in diet

Doses / concentrations 2

Dose / conc.:

70 mg/kg bw/day (nominal)

Remarks:

corresponding to 0.1% dose level in diet

Doses / concentrations 3

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).