Benzenesulfonic acid, 4-C20-24 (even numbered) sec-alkyl derivs., sodium salts

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No reproductive toxicity data with the target substance is available . Data generated with the supporting substance LABS Na is used to cover this endpoint. LABS Na was fed for 84 days to 4 groups of weanling rats for two years (three generations). No significant effects were observed at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was 350 mg/kg bw.

Link to relevant study records

Reference

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:

other: Well documented peer-reviewed publication.

Qualifier:

no guideline followed

Principles of method if other than guideline:

LABS Na (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 (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

Specific details on test material used for the study:

Na-LAS (chain length distribution C10-14)

Species:

rat

Strain:

other: Charles River

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: (P) weanling; (F1) 21 days
- Weight at study initiation: (P) Males: average 59.4-59.9 g; Females: average 57.0-57.3 g; (F1) Males: group weight 183.5-214.2 g; Females: group weight 157.8-193.2 g
- Housing: individual wire bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

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

:

Route of administration:

oral: feed

Vehicle:

other: LAS was administered in feed (Purina Laboratory Meal) - no documentation of dilution prior to addition to meal

Details on mating procedure:

premating exposure period 84 days

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

2 years ( 3 generations)

Frequency of treatment:

continuous in feed

Details on study schedule:

- F1 parental animals not mated until 80-85 days old
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: 107-112 days old

Dose / conc.:

14 mg/kg bw/day

Remarks:

0.02 %, actual ingested

Dose / conc.:

70 mg/kg bw/day

Remarks:

0.1%, actual ingested

Dose / conc.:

350 mg/kg bw/day

Remarks:

0.5%, actual ingested

No. of animals per sex per dose:

50 males and 50 females per group.

Control animals:

yes, concurrent no treatment

Litter observations:

Deformities and number of pups, average body weights, feed consumption, feed efficiency.

Postmortem examinations (parental animals):

Necropsy, body weight, organ to body weight ratios, routine hematology and histology.

Postmortem examinations (offspring):

Necropsy, body weight, organ to body weight ratios, routine hematology and histology.

Reproductive indices:

fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

no effects to body weight were noted in the initial twelve weeks

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

no effects to body weight were noted in the initial twelve weeks

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Description (incidence and severity):

Test substance intake: no effects to average food consumption were noted in the initial twelve weeks

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

No mortality or clinical signs were observed in parental animals. 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. Body weight gains and organ to body weight ratios were normal. Gross examination revealed no abnormalities attributable to the test substance. General reproduction including fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth were normal for all test groups and did not vary from controls.

Dose descriptor:

NOAEL

Effect level:

350 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Critical effects observed:

not specified

Clinical signs:

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

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.

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

350 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Critical effects observed:

not specified

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

350 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Critical effects observed:

not specified

Reproductive effects observed:

not specified

Conclusions:

No significant effects on reproduction were observed at the highest concentration tested.

Executive summary:

LABS Na was fed for 84 days to 4 groups of weanling rats for two years (three generations). No significant effects were observed at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was 350 mg/kg bw (0.5%)

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

350 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

No developmental toxicity study with the target substance is available. Data generated with the supporting substance LABS Na was used to cover this endpoint. In a first developmental toxicity study (performed equivalent to OECD guideline 414) with oral dosing via drinking water, the NOAEL for both maternal toxicity and teratogenicity was set at 300 mg/kg. In a second developmental toxicity study, pregnant female mice were exposed to LABS Na via gavage on days 6 -15 of gestation. The NOAEL for teratogenicity was 300 mg/kg bw/day; the NOAEL for maternal toxicity was 2 mg/kg/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

No developmental toxicity study with the target substance is available. Data generated with the supporting substance LABS Na was used to cover this endpoint.

In a first developmental study, female rats were given LABS Na orally in distilled water from gestation days 6 to 15 during pregnancy. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Pregnancy rates were comparable at all doses. Litter parameters were not significantly affected at any dose. No significant differences were observed in visceral anomalies or skeletal variants, with the exception of a marginal retardation of sternabral ossification at the highest dose. NOAEL was set at 300 mg/kg for both maternal and teratogenicity.

In a second developmental study, pregnant female mice were exposed to LABS Na via gavage on days 6 -15 of gestation (doses 2, 300, 600 mg/kg bw/d). Increased mortality was observed at the two highest doses (300 and 600 mg/kg bw/day). These doses also exhibited retarded weight gain and adverse signs in the necropsy. Pregnancy was comparable, however, for all groups. At doses without maternal toxicity, no differences were observed in any parameters. Because of the very wide range between the 2 mg/kg and 300 mg/kg doses, the maternal NOAEL of 2 mg/kg bw/day must be considered as very conservative and overruled by the NOAEL derived in the 6 months repeated dose study, described above. The NOAEL for teratogenicity was 300 mg/kg bw/day.

Justification for classification or non-classification

Based on the results described, LABS Na is not to be classified as reproductive toxicant.