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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from peer-reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Two year feeding and reproduction study in rats with linear alkylbenzene sulfonate (LAS).
Author:
Buehler, E.V., Newmann, E.A., and King, W.R.
Year:
1971
Bibliographic source:
Toxicol. Appl. Pharmacol. 18:83-91, 1971

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Two-Year Feeding and Reproduction Study of test material in rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzenesulfonic acid, C10-14-alkyl derivs., sodium salts
EC Number:
274-070-8
EC Name:
Benzenesulfonic acid, C10-14-alkyl derivs., sodium salts
Cas Number:
69669-44-9
IUPAC Name:
Benzenesulfonic acid, C10-14-alkyl derivs., sodium salts
Test material form:
solid

Test animals

Species:
rat
Strain:
other: Charles River
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
No data available
Details on mating procedure:
- M/F ratio per cage: 20: 20
- Length of cohabitation: 17 days
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: No data available
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.: No data available
- Further matings after two unsuccessful attempts: No data available
- After successful mating each pregnant female was caged (how): No data available
- Any other deviations from standard protocol: No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: 2 years
Premating exposure period: male: 84 days, female: 84 days
Duration of the test: 3 generations
Frequency of treatment:
continuous in feed
Details on study schedule:
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.
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Remarks:
equivalent to 0.0% (control)
Dose / conc.:
14 mg/kg bw/day
Remarks:
equivalent to 0.02%
Dose / conc.:
70 mg/kg bw/day
Remarks:
equivalent to 0.1%
Dose / conc.:
350 mg/kg bw/day
Remarks:
equivalent to 0.5%
No. of animals per sex per dose:
Total:400
0 mg/kg bw d (control): 50 males and 50 females
14 mg/kg bw d: 50 males and 50 females
70 mg/kg bw d: 50 males and 50 females
350 mg/kg bw d: 50 males and 50 females
Control animals:
yes
Details on study design:
No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: No data
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OTHER:
HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined.: No data

Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
GROSS NECROPSY: Yes


Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:

GROSS NECROPSY: yes
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]

HISTOPATHOLOGY / ORGAN WEIGTHS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
Statistics:
No data available
Reproductive indices:
All reproductive parameters, including fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth were measured.
Offspring viability indices:
No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No definitive adverse effects due to the test material were noted in the haematology and pathology.
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:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
General reproduction including fertility gestation, parturition, neonatal viability, lactation, and post-weaning growth was normal for all test groups and did not deviate from the controls in each generation.

Details on results (P0)

General reproduction including fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth was normal for all test groups and did not deviate from the controls in each generation. No gross abnormalities were noted. No definitive adverse effects due to the test material were noted in the haematology and pathology.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
350 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
haematology
gross pathology
reproductive performance
other: No effects were noted.
Remarks on result:
other: No effects on reproductive performance

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No definitive adverse effects due to the test material were noted in the haematology and pathology.
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:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No gross abnormalities were noted.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
General reproduction including fertility gestation, parturition, neonatal viability, lactation, and post-weaning growth was normal for all test groups and did not deviate from the controls in each generation.

Details on results (P1)

General reproduction including fertility gestation, parturition, neonatal viability, lactation, and post-weaning growth was normal for all test groups and did not deviate from the controls in each generation. No gross abnormalities were noted. No definitive adverse effects due to the test material were noted in the haematology and pathology.

Effect levels (P1)

Dose descriptor:
NOAEL
Effect level:
350 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
haematology
gross pathology
reproductive performance
other: No effects were noted.
Remarks on result:
other: No effects on reproductive performance

Target system / organ toxicity (P1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

General reproduction including neonatal viability and post-weaning growth was normal for all test groups and did not deviate from the controls.

Effect levels (F1)

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 definitive adverse effects due to the test material were noted.
Remarks on result:
other: No effects on developmental parameters

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F2 generation

General toxicity (F2)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Details on results (F2)

General reproduction including neonatal viability and post-weaning growth was normal for all test groups and did not deviate from the controls.

Effect levels (F2)

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 definitive adverse effects due to the test material were noted.
Remarks on result:
other: No effects on developmental parameters was observed

Target system / organ toxicity (F2)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
Under the condition of the study, the reproductive NOAEL for test substance was considered to be 350 mg/kg bw/day.
Executive summary:

In a three generation reproduction study, rats were given the test substance in the diet for approximately 2 years (Buehler et al. 1971). Four groups of male and female weanling rats received dietary doses equivalent to 14, 70 and 350 mg/kg bw d, with 50 animals of each sex per dose group. All reproductive parameters, including fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth were normal for all test groups. In addition, no definitive adverse effects in hematology and pathology or gross abnormalities were noted.

Therefore, the reproductive NOAEL is 350 mg/kg bw/day.

NOAEL Parental: = 0.5%. (350 mg/kg bw d)

NOAEL F1 Offspring: = 0.5% (350 mg/kg bw d)

NOAEL F2 Offspring: = 0.5% (350 mg/kg bw d)

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